Robin Augustine

All Publications

• Scaffolds with high oxygen content support osteogenic cell survival under hypoxia. Biomaterials science Augustine, R., Camci-Unal, G. 2023

  Abstract

  Regeneration of large bone defects is a significant clinical challenge with variable success, but tissue engineering strategies are promising for rapid and effective bone regeneration. Maintaining an adequate oxygen level within implanted scaffolds is a major obstacle in bone tissue engineering. We developed a new oxygen-generating scaffold by electrospinning polycaprolactone with calcium peroxide (CaO2) nanocuboids (CPNCs) and characterized the physical, chemical, and biological properties of the resulting composites. Our scaffolds are highly porous and composed of submicron fibers that include CPNC as confirmed with XRD and FTIR analyses. Scaffolds containing CPNC provided controlled oxygen release for 14-days and supported cell proliferation while protecting preosteoblasts from hypoxia-induced cell death. Oxygen-generating scaffolds also facilitated bone mimetic defect contraction in vitro. The results suggest that our approach can be used to develop tissue-engineered products which target bone defects.

  View details for DOI 10.1039/d3bm00650f

  View details for PubMedID 37401619

• Harnessing the potential of oxygen-generating materials and their utilization in organ-specific delivery of oxygen BIOMATERIALS SCIENCE Nikolopoulos, V. K., Augustine, R., Camci-Unal, G. 2023; 11 (5): 1567-1588

  Abstract

  The limited availability of transplantable organs hinders the success of patient treatment through organ transplantation. In addition, there are challenges with immune rejection and the risk of disease transmission when receiving organs from other individuals. Tissue engineering aims to overcome these challenges by generating functional three-dimensional (3D) tissue constructs. When developing tissues or organs of a particular shape, structure, and size as determined by the specific needs of the therapeutic intervention, a tissue specific oxygen supply to all parts of the tissue construct is an utmost requirement. Moreover, the lack of a functional vasculature in engineered tissues decreases cell survival upon implantation in the body. Oxygen-generating materials can alleviate this challenge in engineered tissue constructs by providing oxygen in a sustained and controlled manner. Oxygen-generating materials can be incorporated into 3D scaffolds allowing the cells to receive and utilize oxygen efficiently. In this review, we present an overview of the use of oxygen-generating materials in various tissue engineering applications in an organ specific manner as well as their potential use in the clinic.

  View details for DOI 10.1039/d2bm01329k

  View details for Web of Science ID 000916810200001

  View details for PubMedID 36688522

  View details for PubMedCentralID PMC10015602

• Hydrogel-Impregnated Self-Oxygenating Electrospun Scaffolds for Bone Tissue Engineering Bioengineering Augustine, R., Nikolopoulos, V. K., Camci-Unal, G. 2023; 10 (7)

  View details for DOI 10.3390/bioengineering10070854

• Air-jet spun PHBV/PCL blend tissue engineering scaffolds exhibit improved mechanical properties and cell proliferation Results in Materials Kalva, S. N., Dalvi, Y. B., P, N., Varghese, R., Ahammed, I., Augustine, R., Hasan, A. 2023

  View details for DOI 10.1016/j.rinma.2023.100415

• Air-jet spun tissue engineering scaffolds incorporated with diamond nanosheets with improved mechanical strength and biocompatibility COLLOIDS AND SURFACES B-BIOINTERFACES Augustine, R., Kalva, S., Dalvi, Y. B., Varghese, R., Chandran, M., Hasan, A. 2023; 221: 112958

  Abstract

  The development of highly porous cell supportive polymeric scaffolds with sufficient mechanical strength has always been a challenging task in tissue engineering. The widely used nanofiber fabrication methods like electrospinning are time consuming and the obtained nanofibrous scaffolds are generally consist of compactly packed fibers, which affect proper cell penetration. On the other hand, air-jet spinning is an upcoming, less explored alternative approach for generating loosely arranged nanofibrous scaffolds within short time. However, air-jet spun scaffolds show inferior mechanical properties due to loosely organized fibers. Herein, we report the fabrication and detailed characterization of polycaprolactone (PCL) tissue engineering scaffolds loaded with diamond nanosheets (DNS) by air-jet spinning. Our results showed that the inclusion of DNS could improve the mechanical strength of the scaffolds. In vitro biocompatibility, and in vivo implantation studies demonstrated that PCL-DNS scaffolds are highly biocompatible and are suitable for tissue engineering applications. Our studies showed that mammalian cells can proliferate well in the presence of PCL-DNS scaffolds and the nanocomposite scaffolds implanted in rats did not show any considerable adverse effects. Overall, the findings show that the developed novel air-jet spun PCL-DNS nanocomposite scaffolds can be used as cell supportive scaffolds for various tissue engineering applications.

  View details for DOI 10.1016/j.colsurfb.2022.112958

  View details for Web of Science ID 000991354400001

  View details for PubMedID 36327774

• Oxygen-generating scaffolds: One step closer to the clinical translation of tissue engineered products CHEMICAL ENGINEERING JOURNAL Augustine, R., Gezek, M., Bostanci, N., Nguyen, A., Camci-Unal, G. 2023; 455

  Abstract

  The lack of oxygen supply in engineered constructs has been an ongoing challenge for tissue engineering and regenerative medicine. Upon implantation of an engineered tissue, spontaneous blood vessel formation does not happen rapidly, therefore, there is typically a limited availability of oxygen in engineered biomaterials. Providing oxygen in large tissue-engineered constructs is a major challenge that hinders the development of clinically relevant engineered tissues. Similarly, maintaining adequate oxygen levels in cell-laden tissue engineered products during transportation and storage is another hurdle. There is an unmet demand for functional scaffolds that could actively produce and deliver oxygen, attainable by incorporating oxygen-generating materials. Recent approaches include encapsulation of oxygen-generating agents such as solid peroxides, liquid peroxides, and fluorinated substances in the scaffolds. Recent approaches to mitigate the adverse effects, as well as achieving a sustained and controlled release of oxygen, are discussed. Importance of oxygen-generating materials in various tissue engineering approaches such as ex vivo tissue engineering, in situ tissue engineering, and bioprinting are highlighted in detail. In addition, the existing challenges, possible solutions, and future strategies that aim to design clinically relevant multifunctional oxygen-generating biomaterials are provided in this review paper.

  View details for DOI 10.1016/j.cej.2022.140783

  View details for Web of Science ID 000906903300001

  View details for PubMedID 36644784

  View details for PubMedCentralID PMC9835968

• Characterization and In vitro biocompatibility analysis of nanocellulose scaffold for tissue engineering application JOURNAL OF POLYMER RESEARCH Unni, R., Varghese, R., Bharat Dalvi, Y., Augustine, R., Latha, M. S., Reshmy, R., Kumar Bhaskaran Nair, H., Hasan, A., Abraham, A., Mathew, T. 2022; 29 (8)

  View details for DOI 10.1007/s10965-022-03072-9

  View details for Web of Science ID 000834837900001

• Halloysite nanotube and chitosan polymer composites: Physicochemical and drug delivery properties JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY Paul, A., Augustine, R., Hasan, A., Zahid, A., Thomas, S., Agatemor, C., Ghosal, K. 2022; 72

  View details for DOI 10.1016/j.jddst.2022.103380

  View details for Web of Science ID 000803842000002

• Nitric oxide-releasing biomaterials for promoting wound healing in impaired diabetic wounds: State of the art and recent trends BIOMEDICINE & PHARMACOTHERAPY Ahmed, R., Augustine, R., Chaudhry, M., Akhtar, U. A., Zahid, A., Tariq, M., Falahati, M., Ahmad, I. S., Hasan, A. 2022; 149: 112707

  Abstract

  Impaired diabetic wounds are serious pathophysiological complications associated with persistent microbial infections including failure in the closure of wounds, and the cause of a high frequency of lower limb amputations. The healing of diabetic wounds is attenuated due to the lack of secretion of growth factors, prolonged inflammation, and/or inhibition of angiogenic activity. Diabetic wound healing can be enhanced by supplying nitric oxide (NO) endogenously or exogenously. NO produced inside the cells by endothelial nitric oxide synthase (eNOS) naturally aids wound healing through its beneficial vasculogenic effects. However, during hyperglycemia, the activity of eNOS is affected, and thus there becomes an utmost need for the topical supply of NO from exogenous sources. Thus, NO-donors that can release NO are loaded into wound healing patches or wound coverage matrices to treat diabetic wounds. The burst release of NO from its donors is prevented by encapsulating them in polymeric hydrogels or nanoparticles for supplying NO for an extended duration of time to the diabetic wounds. In this article, we review the etiology of diabetic wounds, wound healing strategies, and the role of NO in the wound healing process. We further discuss the challenges faced in translating NO-donors as a clinically viable nanomedicine strategy for the treatment of diabetic wounds with a focus on the use of biomaterials for the encapsulation and in vivo controlled delivery of NO-donors.

  View details for DOI 10.1016/j.biopha.2022.112707

  View details for Web of Science ID 000791198800009

  View details for PubMedID 35303565

• Cisplatin encapsulated nanoparticles from polymer blends for anti-cancer drug delivery NEW JOURNAL OF CHEMISTRY Joshy, K. S., Augustine, R., Hasan, A., Zahid, A., Alex, S. M., Dalvi, Y. B., Mraiche, F., Thomas, S., Kalarikkal, N., Chi, H. 2022; 46 (12): 5819-5829

  View details for DOI 10.1039/d1nj04311k

  View details for Web of Science ID 000765858100001

• Spatial mapping of cancer tissues by OMICS technologies BIOCHIMICA ET BIOPHYSICA ACTA-REVIEWS ON CANCER Ahmed, R., Augustine, R., Valera, E., Ganguli, A., Mesaeli, N., Ahmad, I. S., Bashir, R., Hasan, A. 2022; 1877 (1): 188663

  Abstract

  Spatial mapping of heterogeneity in gene expression in cancer tissues can improve our understanding of cancers and help in the rapid detection of cancers with high accuracy and reliability. Significant advancements have been made in recent years in OMICS technologies, which possess the strong potential to be applied in the spatial mapping of biopsy tissue samples and their molecular profiling to a single-cell level. The clinical application of OMICS technologies in spatial profiling of cancer tissues is also advancing. The current review presents recent advancements and prospects of applying OMICS technologies to the spatial mapping of various analytes in cancer tissues. We benchmark the current state of the art in the field to advance existing OMICS technologies for high throughput spatial profiling. The factors taken into consideration include spatial resolution, types of biomolecules, number of different biomolecules that can be detected from the same assay, labeled versus label-free approaches, and approximate time required for each assay. Further advancements are still needed for the widespread application of OMICs technologies in performing fast and high throughput spatial mapping of cancer tissues as well as their effective use in research and clinical applications.

  View details for DOI 10.1016/j.bbcan.2021.188663

  View details for Web of Science ID 000820576700001

  View details for PubMedID 34861353

• Increased complications of COVID-19 in people with cardiovascular disease: Role of the renin-angiotensin-aldosterone system (RAAS) dysregulation CHEMICO-BIOLOGICAL INTERACTIONS Augustine, R., Abhilash, Nayeem, A., Salam, S., Augustine, P., Dan, P., Maureira, P., Mraiche, F., Gentile, C., Hansbro, P. M., McClements, L., Hasan, A. 2022; 351: 109738

  Abstract

  The rapid spread of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) that causes coronavirus disease 2019 (COVID-19), has had a dramatic negative impact on public health and economies worldwide. Recent studies on COVID-19 complications and mortality rates suggest that there is a higher prevalence in cardiovascular diseases (CVD) patients. Past investigations on the associations between pre-existing CVDs and susceptibility to coronavirus infections including SARS-CoV and the Middle East Respiratory Syndrome coronavirus (MERS-CoV), have demonstrated similar results. However, the underlying mechanisms are poorly understood. This has impeded adequate risk stratification and treatment strategies for CVD patients with SARS-CoV-2 infections. Generally, dysregulation of the expression of angiotensin-converting enzyme (ACE) and the counter regulator, angiotensin-converting enzyme 2 (ACE2) is a hallmark of cardiovascular risk and CVD. ACE2 is the main host receptor for SARS-CoV-2. Although further studies are required, dysfunction of ACE2 after virus binding and dysregulation of the renin-angiotensin-aldosterone system (RAAS) signaling may worsen the outcomes of people affected by COVID-19 and with preexisting CVD. Here, we review the current knowledge and outline the gaps related to the relationship between CVD and COVID-19 with a focus on the RAAS. Improved understanding of the mechanisms regulating viral entry and the role of RAAS may direct future research with the potential to improve the prevention and management of COVID-19.

  View details for DOI 10.1016/j.cbi.2021.109738

  View details for Web of Science ID 000721098600001

  View details for PubMedID 34740598

  View details for PubMedCentralID PMC8563522

• Stem cells based in vitro models: trends and prospects in biomaterials cytotoxicity studies BIOMEDICAL MATERIALS Ahmed, U., Ahmed, R., Masoud, M., Tariq, M., Ashfaq, U., Augustine, R., Hasan, A. 2021; 16 (4): 042003

  Abstract

  Advanced biomaterials are increasingly used for numerous medical applications from the delivery of cancer-targeted therapeutics to the treatment of cardiovascular diseases. The issues of foreign body reactions induced by biomaterials must be controlled for preventing treatment failure. Therefore, it is important to assess the biocompatibility and cytotoxicity of biomaterials on cell culture systems before proceeding to in vivo studies in animal models and subsequent clinical trials. Direct use of biomaterials on animals create technical challenges and ethical issues and therefore, the use of non-animal models such as stem cell cultures could be useful for determination of their safety. However, failure to recapitulate the complex in vivo microenvironment have largely restricted stem cell cultures for testing the cytotoxicity of biomaterials. Nevertheless, properties of stem cells such as their self-renewal and ability to differentiate into various cell lineages make them an ideal candidate for in vitro screening studies. Furthermore, the application of stem cells in biomaterials screening studies may overcome the challenges associated with the inability to develop a complex heterogeneous tissue using primary cells. Currently, embryonic stem cells, adult stem cells, and induced pluripotent stem cells are being used as in vitro preliminary biomaterials testing models with demonstrated advantages over mature primary cell or cell line based in vitro models. This review discusses the status and future directions of in vitro stem cell-based cultures and their derivatives such as spheroids and organoids for the screening of their safety before their application to animal models and human in translational research.

  View details for DOI 10.1088/1748-605X/abe6d8

  View details for Web of Science ID 000626872200001

  View details for PubMedID 33686970

• Imaging cancer cells with nanostructures: Prospects of nanotechnology driven non-invasive cancer diagnosis. Advances in colloid and interface science Augustine, R., Mamun, A. A., Hasan, A., Salam, S. A., Chandrasekaran, R., Ahmed, R., Thakor, A. S. 2021; 294: 102457

  Abstract

  The application of nanostructured materials in medicine is a rapidly evolving area of research that includes both the diagnosis and treatment of various diseases. Metals, metal oxides and carbon-based nanomaterials have shown much promise in medical technological advancements due to their tunable physical, chemical and biological properties. The nanoscale properties, especially the size, shape, surface chemistry and stability makes them highly desirable for diagnosing and treating various diseases, including cancers. Major applications of nanomaterials in cancer diagnosis include in vivo bioimaging and molecular marker detection, mainly as image contrast agents using modalities such as radio, magnetic resonance, and ultrasound imaging. When a suitable targeting ligand is attached on the nanomaterial surface, it can help pinpoint the disease site during imaging. The application of nanostructured materials in cancer diagnosis can help in the early detection, treatment and patient follow-up . This review aims to gather and present the information regarding the application of nanotechnology in cancer diagnosis. We also discuss the challenges and prospects regarding the application of nanomaterials as cancer diagnostic tools.

  View details for DOI 10.1016/j.cis.2021.102457

  View details for PubMedID 34144344

• Development of nitric oxide releasing visible light crosslinked gelatin methacrylate hydrogel for rapid closure of diabetic wounds BIOMEDICINE & PHARMACOTHERAPY Zahid, A., Augustine, R., Dalvi, Y. B., Reshma, K., Ahmed, R., Rehman, S., Marei, H. E., Alfkey, R., Hasan, A. 2021; 140: 111747

  Abstract

  Management of non-healing and slow to heal diabetic wounds is a major concern in healthcare across the world. Numerous techniques have been investigated to solve the issue of delayed wound healing, though, mostly unable to promote complete healing of diabetic wounds due to the lack of proper cell proliferation, poor cell-cell communication, and higher chances of wound infections. These challenges can be minimized by using hydrogel based wound healing patches loaded with bioactive agents. Gelatin methacrylate (GelMA) has been proven to be a highly cell friendly, cell adhesive, and inexpensive biopolymer for various tissue engineering and wound healing applications. In this study, S-Nitroso-N-acetylpenicillamine (SNAP), a nitric oxide (NO) donor, was incorporated in a highly porous GelMA hydrogel patch to improve cell proliferation, facilitate rapid cell migration, and enhance diabetic wound healing. We adopted a visible light crosslinking method to fabricate this highly porous biodegradable but relatively stable patch. Developed patches were characterized for morphology, NO release, cell proliferation and migration, and diabetic wound healing in a rat model. The obtained results indicate that SNAP loaded visible light crosslinked GelMA hydrogel patches can be highly effective in promoting diabetic wound healing.

  View details for DOI 10.1016/j.biopha.2021.111747

  View details for Web of Science ID 000670113900009

  View details for PubMedID 34044276

• Active agents loaded extracellular matrix mimetic electrospun membranes for wound healing applications JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY Kalva, S., Augustine, R., Al Mamun, A., Dalvi, Y., Vijay, N., Hasan, A. 2021; 63

  View details for DOI 10.1016/j.jddst.2021.102500

  View details for Web of Science ID 000670350200003

• Bioengineered microfluidic blood-brain barrier models in oncology research TRANSLATIONAL ONCOLOGY Augustine, R., Aqel, A. H., Kalva, S., Joshy, K. S., Nayeem, A., Hasan, A. 2021; 14 (7): 101087

  Abstract

  Metastasis is the major reason for most brain tumors with up to a 50% chance of occurrence in patients with other types of malignancies. Brain metastasis occurs if cancer cells succeed to cross the 'blood-brain barrier' (BBB). Moreover, changes in the structure and function of BBB can lead to the onset and progression of diseases including neurological disorders and brain-metastases. Generating BBB models with structural and functional features of intact BBB is highly important to better understand the molecular mechanism of such ailments and finding novel therapeutic agents targeting them. Hence, researchers are developing novel in vitro BBB platforms that can recapitulate the structural and functional characteristics of BBB. Brain endothelial cells-based in vitro BBB models have thus been developed to investigate the mechanism of brain metastasis through BBB and facilitate the testing of brain targeted anticancer drugs. Bioengineered constructs integrated with microfluidic platforms are vital tools for recapitulating the features of BBB in vitro closely as possible. In this review, we outline the fundamentals of BBB biology, recent developments in the microfluidic BBB platforms, and provide a concise discussion of diverse types of bioengineered BBB models with an emphasis on the application of them in brain metastasis and cancer research in general. We also provide insights into the challenges and prospects of the current bioengineered microfluidic platforms in cancer research.

  View details for DOI 10.1016/j.tranon.2021.101087

  View details for Web of Science ID 000655587700016

  View details for PubMedID 33865030

  View details for PubMedCentralID PMC8066424

• Novel drug delivery systems based on triaxial electrospinning based nanofibers REACTIVE & FUNCTIONAL POLYMERS Ghosal, K., Augustine, R., Zaszczynska, A., Barman, M., Jain, A., Hasan, A., Kalarikkal, N., Sajkiewicz, P., Thomas, S. 2021; 163

  View details for DOI 10.1016/j.reactfunctpolym.2021.104895

  View details for Web of Science ID 000647681400013

• Stem cell-based approaches in cardiac tissue engineering: controlling the microenvironment for autologous cells BIOMEDICINE & PHARMACOTHERAPY Augustine, R., Dan, P., Hasan, A., Khalaf, I., Prasad, P., Ghosal, K., Gentile, C., McClements, L., Maureira, P. 2021; 138: 111425

  Abstract

  Cardiovascular disease is one of the leading causes of mortality worldwide. Cardiac tissue engineering strategies focusing on biomaterial scaffolds incorporating cells and growth factors are emerging as highly promising for cardiac repair and regeneration. The use of stem cells within cardiac microengineered tissue constructs present an inherent ability to differentiate into cell types of the human heart. Stem cells derived from various tissues including bone marrow, dental pulp, adipose tissue and umbilical cord can be used for this purpose. Approaches ranging from stem cell injections, stem cell spheroids, cell encapsulation in a suitable hydrogel, use of prefabricated scaffold and bioprinting technology are at the forefront in the field of cardiac tissue engineering. The stem cell microenvironment plays a key role in the maintenance of stemness and/or differentiation into cardiac specific lineages. This review provides a detailed overview of the recent advances in microengineering of autologous stem cell-based tissue engineering platforms for the repair of damaged cardiac tissue. A particular emphasis is given to the roles played by the extracellular matrix (ECM) in regulating the physiological response of stem cells within cardiac tissue engineering platforms.

  View details for DOI 10.1016/j.biopha.2021.111425

  View details for Web of Science ID 000641386500002

  View details for PubMedID 33756154

• 3D Bioprinted cancer models: Revolutionizing personalized cancer therapy TRANSLATIONAL ONCOLOGY Augustine, R., Kalva, S., Ahmad, R., Zahid, A., Hasan, S., Nayeem, A., McClements, L., Hasan, A. 2021; 14 (4): 101015

  Abstract

  After cardiovascular disease, cancer is the leading cause of death worldwide with devastating health and economic consequences, particularly in developing countries. Inter-patient variations in anti-cancer drug responses further limit the success of therapeutic interventions. Therefore, personalized medicines approach is key for this patient group involving molecular and genetic screening and appropriate stratification of patients to treatment regimen that they will respond to. However, the knowledge related to adequate risk stratification methods identifying patients who will respond to specific anti-cancer agents is still lacking in many cancer types. Recent advancements in three-dimensional (3D) bioprinting technology, have been extensively used to generate representative bioengineered tumor in vitro models, which recapitulate the human tumor tissues and microenvironment for high-throughput drug screening. Bioprinting process involves the precise deposition of multiple layers of different cell types in combination with biomaterials capable of generating 3D bioengineered tissues based on a computer-aided design. Bioprinted cancer models containing patient-derived cancer and stromal cells together with genetic material, extracellular matrix proteins and growth factors, represent a promising approach for personalized cancer therapy screening. Both natural and synthetic biopolymers have been utilized to support the proliferation of cells and biological material within the personalized tumor models/implants. These models can provide a physiologically pertinent cell-cell and cell-matrix interactions by mimicking the 3D heterogeneity of real tumors. Here, we reviewed the potential applications of 3D bioprinted tumor constructs as personalized in vitro models in anticancer drug screening and in the establishment of precision treatment regimens.

  View details for DOI 10.1016/j.tranon.2021.101015

  View details for Web of Science ID 000626637500001

  View details for PubMedID 33493799

  View details for PubMedCentralID PMC7823217

• Gelatin-methacryloyl hydrogel based in vitro blood-brain barrier model for studying breast cancer-associated brain metastasis PHARMACEUTICAL DEVELOPMENT AND TECHNOLOGY Augustine, R., Zahid, A., Mraiche, F., Alam, K., Al Moustafa, A., Hasan, A. 2021; 26 (4): 490-500

  Abstract

  Breast cancer is one of the leading causes of brain metastasis. Metastasis to the brain occurs if cancer cells manage to traverse the 'blood-brain barrier' (BBB), which is a barrier with a very tight junction (TJ) of endothelial cells between blood circulation and brain tissue. It is highly important to develop novel in vitro BBB models to investigate breast cancer metastasis to the brain to facilitate the screening of chemotherapeutic agents against it. We herein report the development of gelatin methacryloyl (GelMA) modified transwell insert based BBB model composed of endothelial and astrocyte cell layers for testing the efficacy of anti-metastatic agents against breast cancer metastasis to the brain. We characterized the developed model for the morphology and in vitro breast cancer cell migration. Furthermore, we investigated the effect of cisplatin, a widely used chemotherapeutic agent, on the migration of metastatic breast cancer cells using the model. Our results showed that breast cancer cells migrate across the developed BBB model. Cisplatin treatment inhibited the migration of cancer cells across the model. Findings of this study suggest that our BBB model can be used as a suitable tool to investigate breast cancer-associated brain metastasis and to identify suitable therapeutic agents against this.

  View details for DOI 10.1080/10837450.2021.1872624

  View details for Web of Science ID 000618298600001

  View details for PubMedID 33416013

• Stromal cell-derived factor loaded co-electrospun hydrophilic/hydrophobic bicomponent membranes for wound protection and healing RSC ADVANCES Augustine, R., Ur Rehman, S., Joshy, K. S., Hasan, A. 2021; 11 (1): 572-583

  Abstract

  Chronic wounds are one of the key concerns for people with diabetes, frequently leading to infections and non-healing ulcers, and finally resulting in the amputation of limbs/organs. Stromal cell-derived factor 1 (SDF1) is a major chemokine that plays a significant role in tissue repair, vascularization, and wound healing. However, the long-term sustained delivery of SDF1 in a chronic wound environment is a great challenge. In order to facilitate the sustained release of SDF1 in diabetic wounds, it could be incorporated into wound-healing patches. Herein, we report the fabrication of a hydrophilic/hydrophobic bicomponent fiber-based membrane, where SDF1 was encapsulated inside hydrophilic fibers, and its applicability in wound healing. A co-electrospinning technique was employed for the fabrication of polymeric membranes where PVA and PCL form the hydrophilic and hydrophobic components, respectively. Morphological analysis of the developed membranes was conducted via scanning electron microscopy (SEM). The mechanical strength of the membranes was investigated via uniaxial tensile testing. The water uptake capacity of the membranes was also determined to understand the hydrophilicity and exudate uptake capacity of the membranes. To understand the proliferation, viability, and migration of skin-specific cells in the presence of SDF1-loaded membranes, in vitro cell culture experiments were carried out using fibroblasts, keratinocytes, and endothelial cells. The results showed the excellent porous morphology of the developed membranes with distinguishable differences in fiber diameters for the PVA and PCL fibers. The developed membranes possessed enough mechanical strength for use as wound-healing membranes. The co-electrospun membranes showed good exudate uptake capacity. The controlled and extended delivery of SDF1 from the developed membranes was observed over a prolonged period. The SDF1-loaded membranes showed enhanced cell proliferation, cell viability, and cell migration. These biocompatible and biodegradable SDF1-loaded bicomponent membranes with excellent exudate uptake capacity, and cell proliferation and cell migration properties can be exploited as a novel wound-dressing membrane aimed at chronic diabetic wounds.

  View details for DOI 10.1039/d0ra04997b

  View details for Web of Science ID 000614277900062

  View details for PubMedID 35423060

  View details for PubMedCentralID PMC8691117

• Cerium Oxide Nanoparticle-Loaded Gelatin Methacryloyl Hydrogel Wound-Healing Patch with Free Radical Scavenging Activity ACS BIOMATERIALS SCIENCE & ENGINEERING Augustine, R., Zahid, A., Hasan, A., Dalvi, Y., Jacob, J. 2021; 7 (1): 279-290

  Abstract

  Nonhealing wounds in diabetic patients are a critical challenge, which often cause amputation and mortality. High levels of oxidative stress and aberrations in antioxidant defense mechanisms increase the adverse manifestations of diabetes mellitus. In this study, we developed a biodegradable gelatin methacryloyl (GelMA) hydrogel patch incorporated with cerium oxide nanoparticles (CONPs) for promoting diabetic wound healing. The patches were thoroughly characterized for the morphology, physicomechanical properties, free radical scavenging activity, in vitro cell proliferation, and in vivo diabetic wound healing activity. Highly porous and biodegradable patches showed excellent exudate uptake capacity as evident from the many-fold weight gain (400-700 times) when placed in aqueous medium. Results of free radical scavenging assays clearly indicated that the patches loaded with 1-4% w/w CONPs could effectively inactivate experimentally generated free radicals. Obtained results of in vitro cell culture studies clearly indicated that CONP-incorporated patches could favor the proliferation of skin-associated cells such as keratinocytes and fibroblasts. Results of the wound healing study showed that 1% w/w CONP-loaded patches could effectively improve the healing of wounds in diabetic rats. Overall results indicate that CONP-loaded GelMA hydrogels are highly promising materials for developing clinically relevant patches for treating diabetic wounds.

  View details for DOI 10.1021/acsbiomaterials.0c01138

  View details for Web of Science ID 000610825900023

  View details for PubMedID 33320529

• Growth factor loaded in situ photocrosslinkable poly(3-hydroxybutyrate-co-3-hydroxyvalerate)/gelatin methacryloyl hybrid patch for diabetic wound healing MATERIALS SCIENCE & ENGINEERING C-MATERIALS FOR BIOLOGICAL APPLICATIONS Augustine, R., Hasan, A., Dalvi, Y. B., Rehman, S., Varghese, R., Unni, R., Yalcin, H. C., Alfkey, R., Thomas, S., Al Moustafa, A. 2021; 118: 111519

  Abstract

  Management of chronic diabetic ulcers remains as a major challenge in healthcare which requires extensive multidisciplinary approaches to ensure wound protection, management of excess wound exudates and promoting healing. Developing wound healing patches that can act as a protective barrier and support healing is highly needed to manage chronic diabetic ulcers. In order to boost the wound healing potential of patch material, bioactive agents such as growth factors can be used. Porous membranes made of nanofibers generated using electrospinning have potential for application as wound coverage matrices. However, electrospun membranes produced from several biodegradable polymers are hydrophobic and cannot manage the excess exudates produced by chronic wounds. Gelatin-methacryloyl (GelMA) hydrogels absorb excess exudates and provide an optimal biological environment for the healing wound. Epidermal growth factor (EGF) promotes cell migration, angiogenesis and overall wound healing. Poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) membranes provide microbial, thermal and mechanical barrier properties to the wound healing patch. Herein, we developed a biodegradable polymeric patch based on the combination of mechanically stable electrospun PHBV, GelMA hydrogel and EGF for promoting diabetic wound healing. In vitro and in vivo studies were carried out to evaluate the effect of developed patches on cell proliferation, cell migration, angiogenesis and wound healing. Our results showed that EGF loaded patches can promote the migration and proliferation of multiple types of cells (keratinocytes, fibroblasts and endothelial cells) and enhance angiogenesis. In situ development of the patch and subsequent in vivo wound healing study in diabetic rats showed that EGF loaded patches provide rapid healing compared to control wounds. Interestingly, 100 ng EGF per cm2 of the patches was enough to provide favourable cellular response, angiogenesis and rapid diabetic wound healing. Overall results indicate that EGF loaded PHBV-GelMA hybrid patch could be a promising approach to promote diabetic wound healing.

  View details for DOI 10.1016/j.msec.2020.111519

  View details for Web of Science ID 000600852800001

  View details for PubMedID 33255074

• Cellular uptake and retention of nanoparticles: Insights on particle properties and interaction with cellular components MATERIALS TODAY COMMUNICATIONS Augustine, R., Hasan, A., Primavera, R., Wilson, R., Thakor, A. S., Kevadiya, B. D. 2020; 25

  View details for DOI 10.1016/j.mtcomm.2020.101692

  View details for Web of Science ID 000600979700001

• Natural halloysite nanotubes/chitosan based bio-nanocomposite for delivering norfloxacin, an anti-microbial agent in sustained release manner INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES Barman, M., Mahmood, S., Augustine, R., Hasan, A., Thomas, S., Ghosal, K. 2020; 162: 1849-1861

  Abstract

  Applying nanotechnology to deliver drug could result in several benefits such as prolong duration of action, enhancement in overall bioavailability, targeting to specific site, low initial loading dose require, systemic stability enhancement etc. Halloysite is one of those clay minerals showing maximum effectiveness when consider as a nano drug carriers for different kind applications. Here, we have used norfloxacin as the model drug for loading into halloysite nanotube (HNT) for its anti-bacterial activity. Norfloxacin was loaded into halloysites by vacuum operation and sonication. The nanotubes were evaluated using X-ray diffraction (XRD), Fourier-transform infrared spectroscopy (FTIR), transmission electron microscopy (TEM), scanning electron microscopy (SEM), optical microscopy, water absorption studies, cytotoxicity studies, antimicrobial studies and in vitro diffusion studies. SEM, FT-IR and XRD analysis data showed that the norfloxacin was successfully loaded into nanotubes. TEM analysis confirmed loading of norfloxacin in halloysites' lumen. The halloysite/chitosan nanocomposites were prepared by solvent casting and freeze-drying method. SEM analysis revealed compact and rugged surface of nanocomposites due to existing norfloxacin loaded halloysite. FTIR and XRD confirmed formation of nanocomposite. The nanocomposites showed good antimicrobial effect and good biocompatibility in cytotoxicity study. The in-vitro release studies revealed that halloysite/chitosan nanocomposites were able to sustain the drug release. Also, the nanocomposites were stable in various humidity conditions. Therefore, all the outcomes suggest that the prepared nanocomposites can provide enhanced therapeutic benefits and they can be very potential nano vehicle for sustaining drug delivery.

  View details for DOI 10.1016/j.ijbiomac.2020.08.060

  View details for Web of Science ID 000577953700075

  View details for PubMedID 32781129

• Carboxymethylcellulose hybrid nanodispersions for edible coatings with potential anti-cancer properties INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES Joshy, K. S., Augustine, R., Li, T., Snigdha, S., Hasan, A., Komalan, C., Kalarikkal, N., Thomas, S. 2020; 157: 350-358

  Abstract

  Curcumin loaded lipid-polymer hybrid nanoparticles dispersions were fabricated from carboxymethylcellulose, stearic acid, polyethylene glycol and sesame oil using emulsion solvent evaporation method for their possible application as edible coatings for fresh vegetables and fruits. They were characterized by FTIR and TEM analysis. In addition, anti-bacterial, blood compatibility, cytotoxicity and anticancer studies were also carried out. The prepared nanodispersions showed excellent mixed nanostructured morphology with an average size of 94.96 nm. The hybrid nanodispersions showed excellent blood compatibility, non-toxicity and antitumor activity. The synthesized nanoparticle dispersion was employed as an edible coating solution for fresh apples and tomatoes. The hybrid system coated vegetables and fruits shows minimal weight loss after 15 days of storage. Hence, the formulated hybrid nanostructures of CMC are promising as edible coating solution, in addition to possessing the properties to fight cancer.

  View details for DOI 10.1016/j.ijbiomac.2020.04.175

  View details for Web of Science ID 000541109300037

  View details for PubMedID 32348862

• Electrospun chitosan membranes containing bioactive and therapeutic agents for enhanced wound healing INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES Augustine, R., Rehman, S., Ahmed, R., Zahid, A., Sharifi, M., Falahati, M., Hasan, A. 2020; 156: 153-170

  Abstract

  Electrospinning is one of the most promising techniques for generating porous, nonwoven, and submicron fiber-based membranes for various applications such as catalysis, sensing, tissue engineering and wound healing. Wide range of biopolymers including chitosan can be used to generate submicron fibrous membranes. Owing to the extra cellular matrix (ECM) mimicking property, exudate uptake capacity, biocompatibility, antibacterial activity and biodegradability, electrospun membranes based on chitosan loaded with biologically active agents can play important role in wound healing applications. In order to improve the mechanical stability, degradation, antimicrobial property, vascularization potential and wound healing capacity, various active components such as other polymers, therapeutic agents, nanoparticles and biomolecules were introduced. Approaches such as coaxial electrospinning with other polymers have also been tried to improve the properties of chitosan membranes. To improve the mechanical stability under in vivo conditions, various crosslinking strategies ranging from physical, chemical and biological approaches were also tried by researchers. Electrospun chitosan meshes have also been designed in a highly specialized manner with specific functionalities to deal with the challenging wound environment of diabetic and burn wounds. This review provides a detailed overview of electrospun chitosan-based membranes containing various bioactive and therapeutic agents in the perspective of wound healing and skin regeneration.

  View details for DOI 10.1016/j.ijbiomac.2020.03.207

  View details for Web of Science ID 000538104200016

  View details for PubMedID 32229203

• Loop-Mediated Isothermal Amplification (LAMP): A Rapid, Sensitive, Specific, and Cost-Effective Point-of-Care Test for Coronaviruses in the Context of COVID-19 Pandemic. Biology Augustine, R., Hasan, A., Das, S., Ahmed, R., Mori, Y., Notomi, T., Kevadiya, B. D., S Thakor, A. 2020; 9 (8)

  Abstract

  The rampant spread of COVID-19 and the worldwide prevalence of infected cases demand a rapid, simple, and cost-effective Point of Care Test (PoCT) for the accurate diagnosis of this pandemic. The most common molecular tests approved by regulatory bodies across the world for COVID-19 diagnosis are based on Polymerase Chain Reaction (PCR). While PCR-based tests are highly sensitive, specific, and remarkably reliable, they have many limitations ranging from the requirement of sophisticated laboratories, need of skilled personnel, use of complex protocol, long wait times for results, and an overall high cost per test. These limitations have inspired researchers to search for alternative diagnostic methods that are fast, economical, and executable in low-resource laboratory settings. The discovery of Loop-mediated isothermal Amplification (LAMP) has provided a reliable substitute platform for the accurate detection of low copy number nucleic acids in the diagnosis of several viral diseases, including epidemics like Severe Acute Respiratory Syndrome (SARS) and Middle East Respiratory Syndrome (MERS). At present, a cocktail of LAMP assay reagents along with reverse transcriptase enzyme (Reverse Transcription LAMP, RT-LAMP) can be a robust solution for the rapid and cost-effective diagnosis for COVID-19, particularly in developing, and low-income countries. In summary, the development of RT-LAMP based diagnostic tools in a paper/strip format or the integration of this method into a microfluidic platform such as a Lab-on-a-chip may revolutionize the concept of PoCT for COVID-19 diagnosis. This review discusses the principle, technology and past research underpinning the success for using this method for diagnosing MERS and SARS, in addition to ongoing research, and the prominent prospect of RT-LAMP in the context of COVID-19 diagnosis.

  View details for DOI 10.3390/biology9080182

  View details for PubMedID 32707972

• Emerging applications of biocompatible phytosynthesized metal/metal oxide nanoparticles in healthcare JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY Augustine, R., Hasan, A. 2020; 56

  View details for DOI 10.1016/j.jddst.2020.101516

  View details for Web of Science ID 000531521400012

• MXene Nanosheets May Induce Toxic Effect on the Early Stage of Embryogenesis JOURNAL OF BIOMEDICAL NANOTECHNOLOGY Alhussain, H., Augustine, R., Hussein, E. A., Gupta, I., Hasan, A., Al Moustafa, A., Elzatahry, A. 2020; 16 (3): 364-372

  Abstract

  MXene (Ti₃C₂Tx), as a novel 2D material, has produced a great interest due to its promising properties in biomedical applications, nevertheless, there is a lack of studies dedicated to investigate the possible toxic effect of MXene in embryos. Herein, we aim to scrutinize the potential toxicity of MXene nanosheets on the early stage of the embryo as well as angiogenesis. Avian embryos at 3 and 5 days of incubation were used as an experimental model in this investigation. Our findings reveal that MXene may produce adverse effect on the early stage of embryogenesis as ∼46% of MXene-exposed embryos died during 1-5 days after exposure. We also found that MXene at tested concentration inhibits angiogenesis of the chorioallantoic membrane of the embryo after 5 days of incubation. More significantly, RT-PCR analysis of seven genes, which are key regulators of cell proliferation, survival, cell death and angiogenesis, revealed that these genes were deregulated in brain, heart and liver tissues from MXene-treated embryos in comparison with their matched controls. Our study clearly suggests that MXene at studied concentration might induce a toxic effect on the early stage of embryogenesis; nevertheless, more investigations are necessary to understand the effect at low concentrations and elucidate its mechanism at the early stage of normal development.

  View details for DOI 10.1166/jbn.2020.2894

  View details for Web of Science ID 000538938700008

  View details for PubMedID 32493546

• Rapid Antibody-Based COVID-19 Mass Surveillance: Relevance, Challenges, and Prospects in a Pandemic and Post-Pandemic World. Journal of clinical medicine Augustine, R. n., Das, S. n., Hasan, A. n., S, A. n., Abdul Salam, S. n., Augustine, P. n., Dalvi, Y. B., Varghese, R. n., Primavera, R. n., Yassine, H. M., Thakor, A. S., Kevadiya, B. D. 2020; 9 (10)

  Abstract

  The aggressive outbreak of the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) as COVID-19 (coronavirus disease-2019) pandemic demands rapid and simplified testing tools for its effective management. Increased mass testing and surveillance are crucial for controlling the disease spread, obtaining better pandemic statistics, and developing realistic epidemiological models. Despite the advantages of nucleic acid- and antigen-based tests such as accuracy, specificity, and non-invasive approaches of sample collection, they can only detect active infections. Antibodies (immunoglobulins) are produced by the host immune system within a few days after infection and persist in the blood for at least several weeks after infection resolution. Antibody-based tests have provided a substitute and effective method of ultra-rapid detection for multiple contagious disease outbreaks in the past, including viral diseases such as SARS (severe acute respiratory syndrome) and MERS (Middle East respiratory syndrome). Thus, although not highly suitable for early diagnosis, antibody-based methods can be utilized to detect past infections hidden in the population, including asymptomatic ones. In an active community spread scenario of a disease that can provide a bigger window for mass detections and a practical approach for continuous surveillance. These factors encouraged researchers to investigate means of improving antibody-based rapid tests and employ them as reliable, reproducible, sensitive, specific, and economic tools for COVID-19 mass testing and surveillance. The development and integration of such immunoglobulin-based tests can transform the pandemic diagnosis by moving the same out of the clinics and laboratories into community testing sites and homes. This review discusses the principle, technology, and strategies being used in antibody-based testing at present. It also underlines the immense prospect of immunoglobulin-based testing and the efficacy of repeated planned deployment in pandemic management and post-pandemic sustainable screenings globally.

  View details for DOI 10.3390/jcm9103372

  View details for PubMedID 33096742

• Cerium Oxide Nanoparticle Incorporated Electrospun Poly(3-hydroxybutyrate-co-3-hydroxyvalerate) Membranes for Diabetic Wound Healing Applications ACS BIOMATERIALS SCIENCE & ENGINEERING Augustine, R., Hasan, A., Patan, N., Dalvi, Y. B., Varghese, R., Antony, A., Unni, R., Sandhyarani, N., Al Moustafa, A. 2020; 6 (1): 58-70

  Abstract

  Insufficient cell proliferation, cell migration, and angiogenesis are among the major causes for nonhealing of chronic diabetic wounds. Incorporation of cerium oxide nanoparticles (nCeO2) in wound dressings can be a promising approach to promote angiogenesis and healing of diabetic wounds. In this paper, we report the development of a novel nCeO2 containing electrospun poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) membrane for diabetic wound healing applications. In vitro cell adhesion studies, chicken embryo angiogenesis assay, and in vivo diabetic wound healing studies were performed to assess the cell proliferation, angiogenesis, and wound healing potential of the developed membranes. The experimental results showed that nCeO2 containing PHBV membranes can promote cell proliferation and cell adhesion when used as wound dressings. For less than 1% w/w of nCeO2 content, human mammary epithelial cells (HMEC) were adhered parallel to the individual fibers of PHBV. For higher than 1% w/w of nCeO2 content, cells started to flatten and spread over the fibers. In ovo angiogenic assay showed the ability of nCeO2 incorporated PHBV membranes to enhance blood vessel formation. In vivo wound healing study in diabetic rats confirmed the wound healing potential of nCeO2 incorporated PHBV membranes. The study suggests that nCeO2 incorporated PHBV membranes have strong potential to be used as wound dressings to enhance cell proliferation and vascularization and promote the healing of diabetic wounds.

  View details for DOI 10.1021/acsbiomaterials.8b01352

  View details for Web of Science ID 000507429200006

  View details for PubMedID 33463234

• A novel in ovo model to study cancer metastasis using chicken embryos and GFP expressing cancer cells BOSNIAN JOURNAL OF BASIC MEDICAL SCIENCES Augustine, R., Alhussain, H., Hasan, A., Ahmed, M., Yalcin, H. C., Al Moustafa, A. 2020; 20 (1): 140-148

  Abstract

  Cancer metastasis is the leading cause of cancer-related mortality worldwide. To date, several in vitro methodologies have been developed to understand the mechanisms of cancer metastasis and to screen various therapeutic agents against it. Nevertheless, mimicking an in vivo microenvironment in vitro is not possible; while in vivo experiments are complex, expensive and bound with several regulatory requirements. Herein, we report a novel in ovo model that relies on chicken embryo to investigate cancer cell invasion and metastasis to various organs of the body. In this model, we directly injected green fluorescent protein (GFP) expressing cancer cells to the heart of chicken embryo at 3 days of incubation, then monitored cell migration to various organs. To this end, we used a simple tissue processing technique to achieve rapid imaging and quantification of invasive cells. We were able to clearly observe the migration of GFP expressing cancer cells into various organs of chicken embryo. Organ specific variation in cell migration was also observed. Our new slide pressing based tissue processing technique improved the detectability of migrated cells. We herein demonstrate that the use of GFP expressing cancer cells allows easy detection and quantification of migrated cancer cells in the chicken embryo model, which minimizes the time and effort required in this types of studies compared to conventional histopathological analysis. In conclusion, our investigation provides a new cancer metastasis model that can be further improved to include more complex aspects, such as the use of multiple cell lines and anti-metastatic agents, thus opening new horizons in cancer biology and pharmaceutical research.

  View details for DOI 10.17305/bjbms.2019.4372

  View details for Web of Science ID 000512952000017

  View details for PubMedID 31336058

  View details for PubMedCentralID PMC7029200

• Yttrium oxide nanoparticle loaded scaffolds with enhanced cell adhesion and vascularization for tissue engineering applications MATERIALS SCIENCE & ENGINEERING C-MATERIALS FOR BIOLOGICAL APPLICATIONS Augustine, R., Dalvi, Y. B., Nath, Y. K., Varghese, R., Raghuveeran, V., Hasan, A., Thomas, S., Sandhyarani, N. 2019; 103: 109801

  Abstract

  In situ tissue engineering is emerging as a novel approach in tissue engineering to repair damaged tissues by boosting the natural ability of the body to heal itself. This can be achieved by providing suitable signals and scaffolds that can augment cell migration, cell adhesion on the scaffolds and proliferation of endogenous cells that facilitate the repair. Lack of appropriate cell proliferation and angiogenesis are among the major issues associated with the limited success of in situ tissue engineering during in vivo studies. Exploitation of metal oxide nanoparticles such as yttrium oxide (Y2O3) nanoparticles may open new horizons in in situ tissue engineering by providing cues that facilitate cell proliferation and angiogenesis in the scaffolds. In this context, Y2O3 nanoparticles were synthesized and incorporated in polycaprolactone (PCL) scaffolds to enhance the cell proliferation and angiogenic properties. An optimum amount of Y2O3-containing scaffolds (1% w/w) promoted the proliferation of fibroblasts (L-929) and osteoblast-like cells (UMR-106). Results of chorioallantoic membrane (CAM) assay and the subcutaneous implantation studies in rats demonstrated the angiogenic potential of the scaffolds loaded with Y2O3 nanoparticles. Gene expression study demonstrated that the presence of Y2O3 in the scaffolds can upregulate the expression of cell proliferation and angiogenesis related biomolecules such as VEGF and EGFR. Obtained results demonstrated that Y2O3 nanoparticles can perform a vital role in tissue engineering scaffolds to promote cell proliferation and angiogenesis.

  View details for DOI 10.1016/j.msec.2019.109801

  View details for Web of Science ID 000480664900105

  View details for PubMedID 31349469

• Nitric oxide releasing chitosan-poly (vinyl alcohol) hydrogel promotes angiogenesis in chick embryo model INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES Zahid, A., Ahmed, R., Rehman, S., Augustine, R., Tariq, M., Hasan, A. 2019; 136: 901-910

  Abstract

  The lack of angiogenic activity is one of the serious complications of chronic wounds associated with delayed wound closure, chronic ulceration, and subsequent limb amputation. Multiple lines of evidence suggest that nitric oxide (NO) produced endogenously by nitric oxide synthase pathway plays a significant role in angiogenic activity and accelerates wounds closure. In this work, chitosan (CS), polyvinyl alcohol (PVA) and S-nitroso-N-acetyl-DL-penicillamine (SNAP) hydrogel was fabricated to accelerate angiogenesis and promote healing in chronic wounds due to better wound closure potential of CS-PVA hydrogel and angiogenic properties of SNAP. The developed CS-PVA hydrogels loaded with SNAP produced a continuous and sustained supply of NO. 3T3 and HaCaT cells showed a significant increase in cell proliferation with 5‰ SNAP loaded CS-PVA hydrogel compared to the control group. Wound scratch assay resulted in four-fold faster recovery of the scratched wound area and an enhanced degree of angiogenic activity was observed in the chick embryo model with the SNAP incorporated CS-PVA hydrogel compared to the control group. The results depict that the use of CS-PVA hydrogel impregnated with SNAP could be a promising material for promoting angiogenesis followed by accelerated healing of the chronic wounds in burns and diabetic patients.

  View details for DOI 10.1016/j.ijbiomac.2019.06.136

  View details for Web of Science ID 000482533000090

  View details for PubMedID 31229545

• Development of titanium dioxide nanowire incorporated poly(vinylidene fluoride-trifluoroethylene) scaffolds for bone tissue engineering applications JOURNAL OF MATERIALS SCIENCE-MATERIALS IN MEDICINE Augustine, A., Augustine, R., Hasan, A., Raghuveeran, V., Rouxel, D., Kalarikkal, N., Thomas, S. 2019; 30 (8): 96

  Abstract

  Critical size bone defects that do not heal spontaneously are among the major reasons for the disability in majority of people with locomotor disabilities. Tissue engineering has become a promising approach for repairing such large tissue injuries including critical size bone defects. Three-dimension (3D) porous scaffolds based on piezoelectric polymers like poly(vinylidene fluoride-trifluoroethylene) (P(VDF-TrFE)) have received a lot of attention in bone tissue engineering due to their favorable osteogenic properties. Owing to the favourable redox properties, titanium dioxide (TiO2) nanostructures have gained a great deal of attention in bone tissue engineering. In this paper, tissue engineering scaffolds based on P(VDF-TrFE) loaded with TiO2 nanowires (TNW) were developed and evaluated for bone tissue engineering. Wet-chemical method was used for the synthesis of TNW. Obtained TNW were thoroughly characterized for the physicochemical and morphological properties using techniques such as X-Ray diffraction (XRD) analysis and transmission electron microscopy (TEM). Electrospinning was used to produce TNW incorporated P(VDF-TrFE) scaffolds. Developed scaffolds were characterized by state of art techniques such as Scanning Electron Microscopy (SEM), XRD and Differential scanning calorimetry (DSC) analyses. TEM analysis revealed that the obtained TiO2 nanostructures possess nanofibrous morphology with an average diameter of 26 ± 4 nm. Results of characterization of nanocomposite scaffolds confirmed the effective loading of TNW in P(VDF-TrFE) matrix. Fabricated P(VDF-TrFE)/TNW scaffolds possessed good mechanical strength and cytocompatibility. Osteoblast like cells showed higher adhesion and proliferation on the nanocomposite scaffolds. This investigation revealed that the developed P(VDF-TrFE) scaffolds containing TNW can be used as potential scaffolds for bone tissue engineering applications.

  View details for DOI 10.1007/s10856-019-6300-4

  View details for Web of Science ID 000480787400003

  View details for PubMedID 31414231

  View details for PubMedCentralID PMC6694083

• Titanium Nanorods Loaded PCL Meshes with Enhanced Blood Vessel Formation and Cell Migration for Wound Dressing Applications MACROMOLECULAR BIOSCIENCE Augustine, R., Hasan, A., Patan, N., Augustine, A., Dalvi, Y. B., Varghese, R., Unni, R., Kalarikkal, N., Al Moustafa, A., Thomas, S. 2019; 19 (7): e1900058

  Abstract

  Proper management of nonhealing wounds is an imperative clinical challenge. For the effective healing of chronic wounds, suitable wound coverage materials with the capability to accelerate cell migration, cell proliferation, angiogenesis, and wound healing are required to protect the healing wound bed. Biodegradable polymeric meshes are utilized as effective wound coverage materials to protect the wounds from the external environment and prevent infections. Among them, electrospun biopolymeric meshes have got much attention due to their extracellular matrix mimicking morphology, ability to support cell adhesion, and cell proliferation. Herein, electrospun nanocomposite meshes based on polycaprolactone (PCL) and titanium dioxide nanorods (TNR) are developed. TNR incorporated PCL meshes are fabricated by electrospinning technique and characterized by scanning electron microscopy, energy dispersive X-ray spectroscopy, Fourier transform infrared spectroscopy (FTIR) analysis, and X-Ray diffraction (XRD) analysis. In vitro cell culture studies, in ovo angiogenesis assay, in vivo implantation study, and in vivo wound healing study are performed. Interestingly, obtained in vitro and in vivo results demonstrated that the presence of TNR in the PCL meshes greatly improved the cell migration, proliferation, angiogenesis, and wound healing. Owing to the above superior properties, they can be used as excellent biomaterials in wound healing and tissue regeneration applications.

  View details for DOI 10.1002/mabi.201900058

  View details for Web of Science ID 000476756700009

  View details for PubMedID 31183959

• Electrospun polylactic acid/date palm polyphenol extract nanofibres for tissue engineering applications EMERGENT MATERIALS Zadeh, K. M., Luyt, A. S., Zarif, L., Augustine, R., Hasan, A., Messori, M., Hassan, M. K., Yalcin, H. C. 2019; 2 (2): 141-151

  View details for DOI 10.1007/s42247-019-00042-8

  View details for Web of Science ID 000596265500003

• Recent advances in electrospun polycaprolactone based scaffolds for wound healing and skin bioengineering applications MATERIALS TODAY COMMUNICATIONS Joseph, B., Augustine, R., Kalarikkal, N., Thomas, S., Seantier, B., Grohens, Y. 2019; 19: 319-335

  View details for DOI 10.1016/j.mtcomm.2019.02.009

  View details for Web of Science ID 000470091100040

• Therapeutic angiogenesis: From conventional approaches to recent nanotechnology-based interventions MATERIALS SCIENCE AND ENGINEERING C-MATERIALS FOR BIOLOGICAL APPLICATIONS Augustine, R., Prasad, P., Khalaf, I. 2019; 97: 994-1008

  Abstract

  Intentional and regulated induction of blood vessels formation which is generally referred to as therapeutic angiogenesis has a lot of potential in the management of various kinds of ischemic complications as well as in wound healing, bone regeneration and tissue engineering. Conventionally, therapeutic angiogenesis relies on the controlled application of growth factors that helps to initiate the formation of blood vessels in the target tissues and bioengineered constructs. The emergence of nanotechnology in medicine, particularly its application in molecular medicine has the potential for a tremendous progress in the therapeutic angiogenesis interventions. Although a good number of systems, which include growth factor delivery, use of gene therapeutic agents, and nanomaterials, are in experimental or preclinical phase, there is a huge potential for them in the clinical implication in upcoming years. In this article, we review the main advances of therapeutic angiogenesis over the past few years, explore the application prospects and discuss about the principles, approaches, importance and challenges with the aim of facilitating its clinical translation in near future.

  View details for DOI 10.1016/j.msec.2019.01.006

  View details for Web of Science ID 000457952800094

  View details for PubMedID 30678987

• Chitosan ascorbate hydrogel improves water uptake capacity and cell adhesion of electrospun poly(epsilon-caprolactone) membranes INTERNATIONAL JOURNAL OF PHARMACEUTICS Augustine, R., Dan, P., Schlachet, I., Rouxel, D., Menu, P., Sosnik, A. 2019; 559: 420-426

  Abstract

  The most important prerequisites for wound coverage matrices are biocompatibility, adequate porosity, degradability and exudate uptake capacity. A moderate hydrophilicity and exudate uptake capacity can often favour cell adhesion and wound healing potential, however, most of the synthetic polymers like polycaprolactone (PCL) are hydrophobic. Hydrogels based on natural polymers can improve the hydrophilicity and exudate uptake capacity of synthetic dressings and improve healing. In this work, we report the development of chitosan ascorbate-infiltrated electrospun PCL membranes. Our study demonstrated that chitosan ascorbate infiltration improves the hydrophilicity as well as water uptake capacity of the membranes and highly favoured the adhesion of human umbilical vein endothelial cells and human mesenchymal stem cells on the membranes.

  View details for DOI 10.1016/j.ijpharm.2019.01.063

  View details for Web of Science ID 000459871500040

  View details for PubMedID 30738131

• CTGF Loaded Electrospun Dual Porous Core-Shell Membrane For Diabetic Wound Healing INTERNATIONAL JOURNAL OF NANOMEDICINE Augustine, R., Zahid, A., Hasan, A., Wang, M., Webster, T. J. 2019; 14: 8573-8588

  Abstract

  Impairment of wound healing is a major issue in type-2 diabetes that often causes chronic infections, eventually leading to limb and/or organ amputation. Connective tissue growth factor (CTGF) is a signaling molecule with several roles in tissue repair and regeneration including promoting cell adhesion, cell migration, cell proliferation and angiogenesis. Incorporation of CTGF in a biodegradable core-shell fiber to facilitate its sustained release is a novel approach to promote angiogenesis, cell migration and facilitate wound healing. In this paper, we report the development of CTGF encapsulated electrospun dual porous PLA-PVA core-shell fiber based membranes for diabetic wound healing applications.The membranes were fabricated by a core-shell electrospinning technique. CTGF was entrapped within the PVA core which was coated by a thin layer of PLA. The developed membranes were characterized by techniques such as Scanning Electron Microscopy (SEM), Fourier Transform Infrared Spectroscopy (FTIR) and X-Ray Diffraction (XRD) analysis. In vitro cell culture studies using fibroblasts, keratinocytes and endothelial cells were performed to understand the effect of CTGF loaded membranes on cell proliferation, cell viability and cell migration. A chicken chorioallantoic membrane (CAM) assay was performed to determine the angiogenic potential of the membranes.Results showed that the developed membranes were highly porous in morphology with secondary pore formation on the surface of individual fibers. In vitro cell culture studies demonstrated that CTGF loaded core-shell membranes improved cell viability, cell proliferation and cell migration. A sustained release of CTGF from the core-shell fibers was observed for an extended time period. Moreover, the CAM assay showed that core-shell membranes incorporated with CTGF can enhance angiogenesis.Owing to the excellent cell proliferation, migration and angiogenic potential of CTGF loaded core-shell PLA-PVA fibrous membranes, they can be used as an excellent wound dressing membrane for treating diabetic wounds and other chronic ulcers.

  View details for DOI 10.2147/IJN.S224047

  View details for Web of Science ID 000493445200002

  View details for PubMedID 31802870

  View details for PubMedCentralID PMC6827515

• Graphene Oxide Loaded Hydrogel for Enhanced Wound Healing in Diabetic Patients Rehman, S., Augustine, R., Zahid, A., Ahmed, R., Hasan, A., IEEE IEEE. 2019: 3943-3946

  Abstract

  Chronic wound or slow healing of a wound is one of the serious complications in diabetic patients. The decrease in the proliferation and migration of cells such as keratinocytes and fibroblasts is the major reason for the development of such chronic wounds in a diabetic patient. Therefore, designing a wound dressing patch using a biodegradable hydrogel, which can provide a sustained release/delivery of active agents that can support cell proliferation and cell migration, will be highly beneficial for promoting diabetic wound healing. Multiple evidences from both in-vitro and in-vivo studies have shown that graphene oxide (GO) and reduced graphene oxide promote wound healing by promoting migration and proliferation of keratinocyte cells. In addition, GO possesses angiogenic property. Gelatin methacrylate (GelMA) based hydrogels display excellent hydrophilic properties due to the presence of hydrophilic amino, amido, carboxyl, and hydroxyl groups in the polymer chains, which gives them highly porous, soft and flexible structure. In this work, we report the development of hydrogel dressing incorporated with GO to improve wound healing by increasing the proliferation and migration of cells.

  View details for Web of Science ID 000557295304085

  View details for PubMedID 31946735

• Reactive Nitrogen Species Releasing Hydrogel for Enhanced Wound Healing Zahid, A., Ahmed, R., Rehman, S., Augustine, R., Hasan, A., IEEE IEEE. 2019: 3939-3942

  Abstract

  Poor proliferation and migration of fibroblast, keratinocyte and endothelial cells delays the wound healing in diabetic patients and results into chronicity of wounds. Slow or decreased formation of blood vessels is another issue that increases the chronicity of non-healing wounds. These chronic wounds turn into an ulcer that may lead to limb amputation. Recently, nitric oxide (NO) has emerged as a potential agent for accelerating cell migration and proliferation to enhance wound healing. It increases the expression of necessary angiogenic growth factors which stimulates the proliferation and migration of major cell types involved in wound repair. Here we report the synthesis of chitosan (CS), polyvinyl alcohol (PVA) and a NO donor S-nitroso-N-acetyl-DL-penicillamine (SNAP) to enhance the wound healing activities in chronic wounds. A three-fold increase in the proliferation of 3T3 cells was observed with NO-releasing CS-PVA hydrogels. In vitro cell migration assay demonstrated a four-fold faster migration of cells to the scratched area compared to the control group. The results depict that the use of CS-PVA hydrogel impregnated with the NO donor (SNAP) can be a promising material for promoting cell migration and subsequent accelerated healing of the chronic wounds in burns and diabetic patients.

  View details for Web of Science ID 000557295304084

  View details for PubMedID 31946734

• Novel electrospun chitosan/polyvinyl alcohol/zinc oxide nanofibrous mats with antibacterial and antioxidant properties for diabetic wound healing INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES Ahmed, R., Tariq, M., Ali, I., Asghar, R., Khanam, P., Augustine, R., Hasan, A. 2018; 120: 385-393

  Abstract

  Non-healing wound is a serious complication of diabetes, associated with extremely slow wound closure, and a high rate of infection, resulting in amputation or losses of limbs, high health care cost and poor quality of patient's life. In the present study, we hypothesized that nanofiber mats composed of a combination of chitosan, polyvinyl alcohol (PVA) and Zinc oxide (ZnO) could be an effective option for faster healing of diabetic wounds due to the wound healing activities of chitosan-PVA nanofibers and antibacterial properties of ZnO. Nanofiber mats of chitosan, PVA and ZnO were synthesized using electrospinning technique. The developed nanofibrous mats were characterized by scanning electron microscopy (SEM), Fourier-transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), antibacterial and antioxidant assays as well as in vivo wound healing experiments in rabbits. The results revealed that chitosan/PVA/ZnO nanofibrous membranes possessed higher antibacterial potential against E. coli, P. aeruginosa, B. subtilis and S. aureus compared to chitosan/PVA nanofibrous membranes. Moreover, chitosan/PVA/ZnO nanofibrous membranes exhibited higher antioxidant potential compared to chitosan/PVA nanofibrous mats. The in vivo wound healing studies showed that chitosan/PVA/ZnO nanofibrous membranes resulted in accelerated wound healing as compared to chitosan/PVA nanofibers. The current study, thus, reveals that chitosan/PVA/ZnO electrospun scaffolds could be effectively helpful in dressings for diabetic wounds.

  View details for DOI 10.1016/j.ijbiomac.2018.08.057

  View details for Web of Science ID 000452587500047

  View details for PubMedID 30110603

• Nanoceria Can Act as the Cues for Angiogenesis in Tissue Engineering Scaffolds: Toward Next-Generation in Situ Tissue Engineering ACS BIOMATERIALS SCIENCE & ENGINEERING Augustine, R., Dalvi, Y. B., Dan, P., George, N., Helle, D., Varghese, R., Thomas, S., Menu, P., Sandhyarani, N. 2018; 4 (12): 4338-4353

  Abstract

  Next-generation tissue engineering exploits the body's own regenerative capacity by providing an optimal niche via a scaffold for the migration and subsequent proliferation of endogenous cells to the site of injury, enhancing regeneration and healing and bypassing laborious in vitro cell-culturing procedures. Such systems are also required to have a sufficient angiogenic capacity for the subsequent patency of implanted scaffolds. The exploitation of redox properties of nanodimensional ceria (nCeO2) in in situ tissue engineering to promote cell adhesion and angiogenesis is poorly investigated. As a novel strategy, electrospun polycaprolactone based tissue-engineering scaffolds loaded with nCeO2 were developed and evaluated for morphological and physicomechanical features. In addition, in vitro and in vivo studies were performed to show the ability of nCeO2-containing scaffolds to enhance cell adhesion and angiogenesis. These studies confirmed that nCeO2-containing scaffolds supported cell adhesion and angiogenesis better than bare scaffolds. Gene-expression studies had shown that angiogenesis-related factors such as HIF1α and VEGF were up-regulated. Overall results show that incorporation of nCeO2 plays a key role in scaffolds for the enhancement of angiogenesis, cell adhesion, and cell proliferation and can produce a successful outcome in in situ tissue engineering.

  View details for DOI 10.1021/acsbiomaterials.8b01102

  View details for Web of Science ID 000453109000042

  View details for PubMedID 33418829

• Electrospun polyvinyl alcohol membranes incorporated with green synthesized silver nanoparticles for wound dressing applications JOURNAL OF MATERIALS SCIENCE-MATERIALS IN MEDICINE Augustine, R., Hasan, A., Nath, V., Thomas, J., Augustine, A., Kalarikkal, N., Al Moustafa, A., Thomas, S. 2018; 29 (11): 163

  Abstract

  Electrospun membranes have the potential to act as an effective barrier for wounds from the external environment to prevent pathogens. In addition, materials with good antibacterial properties can effectively fight off the invading pathogens. In this paper, we report the development of a novel electrospun polyvinyl alcohol (PVA) membrane containing biosynthesized silver nanoparticle (bAg) for wound dressing applications. Plant extract from a medicinal plant Mimosa pudica was utilized for the synthesis of bAg. Synthesized bAg were characterized by Ultraviolet-Visible (UV) Spectroscopy and Fourier Transform Infrared Spectroscopy (FTIR). The morphology of bAg was obtained from Transmission Electron Microscopy (TEM) and found that they were spherical in morphology with average particle size 7.63 ± 1.2 nm. bAg nanoparticles incorporated PVA membranes were characterized using several physicochemical techniques such as Scanning Electron Microscopy (SEM), Energy Dispersive X-Ray Spectroscopy (EDS) and X-Ray Diffraction (XRD) analysis. Experimental results confirmed the successful incorporation of bAg in PVA fibers. PVA nanofiber membranes incorporated with bAg showed good mechanical strength, excellent exudate uptake capacity, antibacterial activity, blood compatibility and cytocompatibility.

  View details for DOI 10.1007/s10856-018-6169-7

  View details for Web of Science ID 000449288200003

  View details for PubMedID 30392046

• Nanoparticle-in-microparticle oral drug delivery system of a clinically relevant darunavir/ritonavir antiretroviral combination ACTA BIOMATERIALIA Augustine, R., Ashkenazi, D., Arzi, R., Zlobin, V., Shofti, R., Sosnik, A. 2018; 74: 344-359

  Abstract

  Nanonizationhas been extensively investigated to increase theoral bioavailability of hydrophobicdrugsin general andantiretrovirals(ARVs)used inthe therapy of the human immunodeficiency virus (HIV) infection in particular. Weanticipatedthatin the caseofprotease inhibitors, a family of pH-dependent ARVsthatdisplay high aqueous solubility undertheacidconditionsof thestomach andextremely low solubilityunder the neutral ones ofthe small intestine, this strategy might failowing to an uncontrolled dissolution-re-precipitation process that will take place along the gastrointestinal tract.To tackle thisbiopharmaceutical challenge, in this work, wedesigned, produced and fully characterized a novelNanoparticle-in-MicroparticleDelivery System(NiMDS)comprised of pure nanoparticlesofthefirst-line protease inhibitor darunavir(DRV) and itsboosting agentritonavir (RIT) encapsulated within film-coated microparticles.For this, a clinically relevant combination of pure DRV and RIT nanoparticles wassynthesized by a sequential nanoprecipitation/solvent diffusion and evaporation method employing sodium alginateas viscosity stabilizer. Then, pure nanoparticles were encapsulated within calcium alginate/chitosanmicroparticlesthat were film-coated with a series ofpoly(methacrylate) copolymers with differential solubility in the gastrointestinal tract. This coating ensured full stability under gastric-like pH and sustained drug release under intestinal one. PharmacokineticstudiesconductedinalbinoSpragueDawleyratsshowed that DRV/RIT-loadedNiMDSs containing 17% w/w drug loading based on dry weight significantlyincreasedthe oral bioavailabilityof DRVby 2.3-foldwith respect to both theunprocessedandthenanonized DRV/RIT combinations that showed statistically similar performance. Moreover, they highlighted the limited advantage of only drugnanonizationto improve the oral pharmacokinetics of protease inhibitors and the potential of our novel delivery approach to improve the oral pharmacokinetics of nanonized poorly water-soluble drugs displaying pH-dependent solubility.Protease inhibitors (PIs) are gold-standard drugs in many ARV cocktails. Darunavir (DRV) is the latest approved PI and it is included in the 20th WHO Model List of Essential Medicines. PIs poorly-water soluble at intestinal pH and more soluble under gastric conditions. Drug nanonization represents one of the most common nanotechnology strategies to increase dissolution rate of hydrophobic drugs and thus, their oral bioavailability. For instance, pure drug nanosuspensions became the most clinically relevant nanoformulation. However, according to the physicochemical properties of PIs, nanonization does not appear as a very beneficial strategy due to the fast dissolution rate anticipated under the acid conditions of the stomach and their uncontrolled recrystallization and precipitation in the small intestine that might result in the formation of particles of unpredictable size and structure (e.g., crystallinity and polymorphism) and consequently, unknown dissolution rate and bioavailability. In this work, we developed a sequential nanoprecipitation method for the production of pure nanoparticles of DRV and its boosting agent ritonavir in a clinically relevant 8:1 wt ratio using alginate as viscosity stabilizer and used this nanosuspension to produce a novel kind of nanoparticle-in-microparticle delivery system that was fully characterized and the pharmacokinetics assessed in rats. The most significant points of the current manuscript are.

  View details for DOI 10.1016/j.actbio.2018.04.045

  View details for Web of Science ID 000437998200027

  View details for PubMedID 29723705

• Skin bioprinting: a novel approach for creating artificial skin from synthetic and natural building blocks PROGRESS IN BIOMATERIALS Augustine, R. 2018; 7 (2): 77-92

  Abstract

  Significant progress has been made over the past few decades in the development of in vitro-engineered substitutes that mimic human skin, either as grafts for the replacement of lost skin, or for the establishment of in vitro human skin models. Tissue engineering has been developing as a novel strategy by employing the recent advances in various fields such as polymer engineering, bioengineering, stem cell research and nanomedicine. Recently, an advancement of 3D printing technology referred as bioprinting was exploited to make cell loaded scaffolds to produce constructs which are more matching with the native tissue. Bioprinting facilitates the simultaneous and highly specific deposition of multiple types of skin cells and biomaterials, a process that is lacking in conventional skin tissue-engineering approaches. Bioprinted skin substitutes or equivalents containing dermal and epidermal components offer a promising approach in skin bioengineering. Various materials including synthetic and natural biopolymers and cells with or without signalling molecules like growth factors are being utilized to produce functional skin constructs. This technology emerging as a novel strategy to overcome the current bottle-necks in skin tissue engineering such as poor vascularization, absence of hair follicles and sweat glands in the construct.

  View details for DOI 10.1007/s40204-018-0087-0

  View details for Web of Science ID 000448204000001

  View details for PubMedID 29754201

  View details for PubMedCentralID PMC6068049

• Electrospun poly(vinylidene fluoride-trifluoroethylene)/zinc oxide nanocomposite tissue engineering scaffolds with enhanced cell adhesion and blood vessel formation NANO RESEARCH Augustine, R., Dan, P., Sosnik, A., Kalarikkal, N., Tran, N., Vincent, B., Thomas, S., Menu, P., Rouxel, D. 2017; 10 (10): 3358-3376

  View details for DOI 10.1007/s12274-017-1549-8

  View details for Web of Science ID 000410304500009

• Electrospun polycaprolactone (PCL) scaffolds embedded with europium hydroxide nanorods (EHNs) with enhanced vascularization and cell proliferation for tissue engineering applications JOURNAL OF MATERIALS CHEMISTRY B Augustine, R., Nethi, S., Kalarikkal, N., Thomas, S., Patra, C. 2017; 5 (24): 4660-4672

  Abstract

  Electrospun polycaprolactone (PCL) tissue engineering scaffolds have been developed and used for a wide range of tissue engineering applications, where successful incorporation and conservation of the therapeutic activity of the embedded nanoparticles into scaffolds is critically needed for effective tissue engineering. Incorporation of pro-angiogenic nanomaterials to promote vascularization is a novel approach. Our group has well-demonstrated the potent pro-angiogenic properties of europium hydroxide nanorods (EHNs) using in vitro and in vivo systems. In the present study, electrospun PCL tissue engineering scaffolds containing EHNs were fabricated and characterized for various morphological and physico-chemical properties. Furthermore, biological studies showed enhanced cell growth and a greater density of endothelial cells grown on the scaffolds incorporated with EHNs (PCL-EHNs). The PCL-EHNs also exhibited good hemo-compatibility towards blood cells. Fluorescence microscopy and SEM observations showed good endothelial cell adhesion over these scaffolds. The PCL-EHNs demonstrated augmented growth of blood vessels in an in vivo chick embryo angiogenesis model. Furthermore, protein expression studies illustrated promoted angiogenesis of HUVECs on scaffolds in a VEGFR2/Akt mediated signaling cascade. Together, the above observations strongly suggest potent applications of EHN-incorporated PCL scaffolds in promoting angiogenesis/vascularization and their effective use in tissue engineering and vascular disease therapy.

  View details for DOI 10.1039/c7tb00518k

  View details for Web of Science ID 000404070600012

  View details for PubMedID 32264308

• Metal Oxide Nanoparticles as Versatile Therapeutic Agents Modulating Cell Signaling Pathways: Linking Nanotechnology with Molecular Medicine APPLIED MATERIALS TODAY Augustine, R., Mathew, A. P., Sosnik, A. 2017; 7: 91-103

  View details for DOI 10.1016/j.apmt.2017.01.010

  View details for Web of Science ID 000405594100009

• Fabrication and characterization of biosilver nanoparticles loaded calcium pectinate nano-micro dual-porous antibacterial wound dressings PROGRESS IN BIOMATERIALS Augustine, R., Augustine, A., Kalarikkal, N., Thomas, S. 2016; 5 (3-4): 223-235

  Abstract

  Development of materials for medical applications using biologically derived materials by green approaches is emerging as an important focus in the present healthcare scenario. Herein the first time, we report the plant extract mediated ultra-rapid biosynthesis of silver nanoparticles using whole plant extracts of Biophytum sensitivum. Synthesized nanoparticles were immobilized in nano-micro dual-porous calcium pectinate scaffolds for wound dressing application. Pectinate wound dressings containing silver nanoparticles have shown excellent antibacterial property and exudate uptake capacity while being biocompatible to the human cells.

  View details for DOI 10.1007/s40204-016-0060-8

  View details for Web of Science ID 000391207400008

  View details for PubMedID 27995588

  View details for PubMedCentralID PMC5301463

• Challenges in oral drug delivery of antiretrovirals and the innovative strategies to overcome them ADVANCED DRUG DELIVERY REVIEWS Sosnik, A., Augustine, R. 2016; 103: 105-120

  Abstract

  Development of novel drug delivery systems (DDS) represents a promising opportunity to overcome the various bottlenecks associated with the chronic antiretroviral (ARV) therapy of the human immunodeficiency virus (HIV) infection. Oral drug delivery is the most convenient and simplest route of drug administration that involves the swallowing of a pharmaceutical compound with the intention of releasing it into the gastrointestinal tract. In oral delivery, drugs can be formulated in such a way that they are protected from digestive enzymes, acids, etc. and released in different regions of the small intestine and/or the colon. Not surprisingly, with the exception of the subcutaneous enfuvirtide, all the marketed ARVs are administered orally. However, conventional (marketed) and innovative (under investigation) oral delivery systems must overcome numerous challenges, including the acidic gastric environment, and the poor aqueous solubility and physicochemical instability of many of the approved ARVs. In addition, the mucus barrier can prevent penetration and subsequent absorption of the released drug, a phenomenon that leads to lower oral bioavailability and therapeutic concentration in plasma. Moreover, the frequent administration of the cocktail (ARVs are administered at least once a day) favors treatment interruption. To improve the oral performance of ARVs, the design and development of more efficient oral drug delivery systems are called for. The present review highlights various innovative research strategies adopted to overcome the limitations of the present treatment regimens and to enhance the efficacy of the oral ARV therapy in HIV.

  View details for DOI 10.1016/j.addr.2015.12.022

  View details for Web of Science ID 000380083700008

  View details for PubMedID 26772138

• Surface Acoustic Wave Device with Reduced Insertion Loss by Electrospinning P(VDF-TrFE)/ZnO Nanocomposites NANO-MICRO LETTERS Augustine, R., Sarry, F., Kalarikkal, N., Thomas, S., Badie, L., Rouxel, D. 2016; 8 (3): 282-290

  Abstract

  Surface acoustic wave (SAW) devices have been utilized for the sensing of chemical and biological phenomena in microscale for the past few decades. In this study, SAW device was fabricated by electrospinning poly(vinylidenefluoride-co-trifluoroethylene) (P(VDF-TrFE)) incorporated with zinc oxide (ZnO) nanoparticles over the delay line area of the SAW device. The morphology, composition, and crystallinity of P(VDF-TrFE)/ZnO nanocomposites were investigated. After measurement of SAW frequency response, it was found that the insertion loss of the SAW devices incorporated with ZnO nanoparticles was much less than that of the neat polymer-deposited device. The fabricated device was expected to be used in acoustic biosensors to detect and quantify the cell proliferation in cell culture systems.

  View details for DOI 10.1007/s40820-016-0088-2

  View details for Web of Science ID 000376898300010

  View details for PubMedID 30460288

  View details for PubMedCentralID PMC6223672

• Clogging-Free Electrospinning of Polycaprolactone Using Acetic Acid/Acetone Mixture POLYMER-PLASTICS TECHNOLOGY AND ENGINEERING Augustine, R., Kalarikkal, N., Thomas, S. 2016; 55 (5): 518-529

  View details for DOI 10.1080/03602559.2015.1036451

  View details for Web of Science ID 000371927300008

• Electrospun PCL membranes incorporated with biosynthesized silver nanoparticles as antibacterial wound dressings APPLIED NANOSCIENCE Augustine, R., Kalarikkal, N., Thomas, S. 2016; 6 (3): 337-344

  View details for DOI 10.1007/s13204-015-0439-1

  View details for Web of Science ID 000371159300005

• Cell Adhesion on Polycaprolactone Modified by Plasma Treatment INTERNATIONAL JOURNAL OF POLYMER SCIENCE Recek, N., Resnik, M., Motaln, H., Lah-Turnsek, T., Augustine, R., Kalarikkal, N., Thomas, S., Mozetic, M. 2016; 2016

  View details for DOI 10.1155/2016/7354396

  View details for Web of Science ID 000375267400001

• Effect of zinc oxide nanoparticles on the in vitro degradation of electrospun polycaprolactone membranes in simulated body fluid INTERNATIONAL JOURNAL OF POLYMERIC MATERIALS AND POLYMERIC BIOMATERIALS Augustine, R., Kalarikkal, N., Thomas, S. 2016; 65 (1): 28-37

  View details for DOI 10.1080/00914037.2015.1055628

  View details for Web of Science ID 000362723600004

• POLYURONATES AND THEIR APPLICATION IN DRUG DELIVERY AND COSMETICS GREEN POLYMERS AND ENVIRONMENTAL POLLUTION CONTROL Augustine, R., Venugopal, B., Snigdha, S., Kalarikkal, N., Thomas, S., Khalaf, M. N. 2016: 239-269

  View details for Web of Science ID 000386219700009

• MONITORING AND SEPARATION OF FOOD-BORNE PATHOGENS USING MAGNETIC NANOPARTICLES NOVEL APPROACHES OF NANOTECHNOLOGY IN FOOD Augustine, R., Abraham, A., Kalarikkal, N., Thomas, S., Grumezescu, A. M. 2016; 1: 271-312

  View details for DOI 10.1016/B978-0-12-804308-0.00009-1

  View details for Web of Science ID 000471780300012

• Nanomedicine and Tissue Engineering: State of the Art and Recent Trends NANOMEDICINE AND TISSUE ENGINEERING: STATE OF THE ART AND RECENT TRENDS Kalarikkal, N., Augustine, R., Oluwafemi, O. S., Joshy, K. S., Thomas, S. 2016: 1-520

  View details for DOI 10.1201/b19867

  View details for Web of Science ID 000400759400016

• ELECTROSPUN MATRICES FOR BIOMEDICAL APPLICATIONS: RECENT ADVANCES NANOMEDICINE AND TISSUE ENGINEERING: STATE OF THE ART AND RECENT TRENDS Mohanan, D. P., Augustine, R., Kalarikkal, N., Radhakrishnan, E. K., Thomas, S., Kalarikkal, N., Augustine, R., Oluwafemi, O. S., Joshy, K. S., Thomas, S. 2016: 365-390

  View details for Web of Science ID 000400759400012

• NANOMEDICINE: FROM CONCEPT TO REALITY NANOMEDICINE AND TISSUE ENGINEERING: STATE OF THE ART AND RECENT TRENDS Rakhimol, K. R., Augustine, R., Thomas, S., Kalarikkal, N., Kalarikkal, N., Augustine, R., Oluwafemi, O. S., Joshy, K. S., Thomas, S. 2016: 1-30

  View details for Web of Science ID 000400759400002

• TISSUE ENGINEERING: PRINCIPLES, RECENT TRENDS AND THE FUTURE NANOMEDICINE AND TISSUE ENGINEERING: STATE OF THE ART AND RECENT TRENDS Mathew, A. P., Augustine, R., Kalarikkal, N., Thomas, S., Kalarikkal, N., Augustine, R., Oluwafemi, O. S., Joshy, K. S., Thomas, S. 2016: 31-82

  View details for Web of Science ID 000400759400003

• CUTANEOUS WOUND CARE: GRAFTS TO TISSUE-ENGINEERED SKIN SUBSTITUTES NANOMEDICINE AND TISSUE ENGINEERING: STATE OF THE ART AND RECENT TRENDS Augustine, R., Venugopal, B., Kalarikkal, N., Thomas, S., Kalarikkal, N., Augustine, R., Oluwafemi, O. S., Joshy, K. S., Thomas, S. 2016: 493-520

  View details for Web of Science ID 000400759400015

• Gentamicin Loaded Electrospun Poly(epsilon-Caprolactone)/TiO2 Nanocomposite Membranes with Antibacterial Property against Methicillin Resistant Staphylococcus aureus POLYMER-PLASTICS TECHNOLOGY AND ENGINEERING Nandagopal, S., Augustine, R., George, S. C., Jayachandran, V. P., Kalarikkal, N., Thomas, S. 2016; 55 (17): 1785-1796

  View details for DOI 10.1080/03602559.2016.1171877

  View details for Web of Science ID 000389037300001

• Electrospun poly(epsilon-caprolactone)-based skin substitutes: In vivo evaluation of wound healing and the mechanism of cell proliferation JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART B-APPLIED BIOMATERIALS Augustine, R., Dominic, E., Reju, I., Kaimal, B., Kalarikkal, N., Thomas, S. 2015; 103 (7): 1445-1454

  Abstract

  In the present study, we have fabricated electrospun poly(ε-caprolactone)-based membranes, characterized and studied the in vivo cell migration and proliferation and wound healing activity. Moreover, we did not seed any cells prior to the animal implantation and we could observe excellent fibroblast attachment and cell proliferation. Further full thickness excision wound on guinea pig completely healed within 35 days. We could reach in an assumption that the enhanced cell proliferation and wound healing might be due to the surface degradation of the polymer under physiological conditions and the formation of functional groups like hydroxyl and carboxyl groups that promoted cell proliferation in a cell adhesion protein mediated mechanism. This study is a novel tissue engineering concept for the reconstruction of a damaged tissue without the in vitro cell seeding and proliferation prior to the in vivo implantation.

  View details for DOI 10.1002/jbm.b.33325

  View details for Web of Science ID 000363693600012

  View details for PubMedID 25418134

• An In vitro Method for the Determination of Microbial Barrier Property (MBP) of Porous Polymeric Membranes for Skin Substitute and Wound Dressing Applications TISSUE ENGINEERING AND REGENERATIVE MEDICINE Augustine, R., Kalarikkal, N., Thomas, S. 2015; 12 (1): 12-19

  View details for DOI 10.1007/s13770-014-0032-9

  View details for Web of Science ID 000351867900002

• Dose-Dependent Effects of Gamma Irradiation on the Materials Properties and Cell Proliferation of Electrospun Polycaprolactone Tissue Engineering Scaffolds INTERNATIONAL JOURNAL OF POLYMERIC MATERIALS AND POLYMERIC BIOMATERIALS Augustine, R., Saha, A., Jayachandran, V. P., Thomas, S., Kalarikkal, N. 2015; 64 (10): 526-533

  View details for DOI 10.1080/00914037.2014.977900

  View details for Web of Science ID 000349681800004

• Advancement of wound care from grafts to bioengineered smart skin substitutes PROGRESS IN BIOMATERIALS Augustine, R., Kalarikkal, N., Thomas, S. 2014; 3 (2-4): 103-113

  Abstract

  This review gives a brief description on the skin and its essential functions, damages or injury which are common to the skin and the role of skin substitute to replace the functions of the skin soon after an injury. Skin substitutes have crucial role in the management of deep dermal and full thickness wounds. At present, there is no skin substitute in the market that can replace all the functions of skin 'and the research is still continuing for a better alternative. This review is an attempt to recollect and report the past efforts including skin grafting and recent trends like use of bioengineered smart skin substitutes in wound care. Incorporation functional moieties like antimicrobials and wound healing agents are also described.

  View details for DOI 10.1007/s40204-014-0030-y

  View details for Web of Science ID 000214808700002

  View details for PubMedID 29470769

  View details for PubMedCentralID PMC5299852

• A facile and rapid method for the black pepper leaf mediated green synthesis of silver nanoparticles and the antimicrobial study APPLIED NANOSCIENCE Augustine, R., Kalarikkal, N., Thomas, S. 2014; 4 (7): 809-818

  View details for DOI 10.1007/s13204-013-0260-7

  View details for Web of Science ID 000209843800005

• Electrospun polycaprolactone/ZnO nanocomposite membranes as biomaterials with antibacterial and cell adhesion properties JOURNAL OF POLYMER RESEARCH Augustine, R., Malik, H., Singhal, D., Mukherjee, A., Malakar, D., Kalarikkal, N., Thomas, S. 2014; 21 (3)

  View details for DOI 10.1007/s10965-013-0347-6

  View details for Web of Science ID 000331723500001

• Investigation of angiogenesis and its mechanism using zinc oxide nanoparticle-loaded electrospun tissue engineering scaffolds RSC ADVANCES Augustine, R., Dominic, E., Reju, I., Kaimal, B., Kalarikkal, N., Thomas, S. 2014; 4 (93): 51528-51536

  View details for DOI 10.1039/c4ra07361d

  View details for Web of Science ID 000344387400062

• Electrospun polycaprolactone membranes incorporated with ZnO nanoparticles as skin substitutes with enhanced fibroblast proliferation and wound healing RSC ADVANCES Augustine, R., Dominic, E., Reju, I., Kaimal, B., Kalarikkal, N., Thomas, S. 2014; 4 (47): 24777-24785

  View details for DOI 10.1039/c4ra02450h

  View details for Web of Science ID 000338042800047

• Synthesis and characterization of silver nanoparticles and its immobilization on alginate coated sutures for the prevention of surgical wound infections and the in vitro release studies INTERNATIONAL JOURNAL OF NANO DIMENSION Augustine, R., Rajarathinam, K. 2012; 2 (3): 205-212

  View details for DOI 10.7508/ijnd.2011.03.009

  View details for Web of Science ID 000409694800009

• Extracellular biosynthesis of iron oxide nanoparticles by Bacillus subtilis strains isolated from rhizosphere soil BIOTECHNOLOGY AND BIOPROCESS ENGINEERING Sundaram, P., Augustine, R., Kannan, M. 2012; 17 (4): 835-840

  View details for DOI 10.1007/s12257-011-0582-9

  View details for Web of Science ID 000307972400021