Artem Trotsyuk is a Ph.D. candidate in Dr. Geoffrey Gurtner’s laboratory in the Department of Surgery at Stanford University. He is co-advised by Dr. Zhenan Bao in the Department of Chemical Engineering. His advisors include Dr. Russ Altman and Dr. Michael Snyder. His research interests lie in bioengineering, gene editing, wearables, CRISPR therapy and regenerative medicine. Currently, he is using bioengineering tools coupled with artificial intelligence to improve wound healing outcomes in diabetic patients. He is working on developing a smart bandage that implements a closed-loop AI processing system for sensing and therapeutic delivery into a wound bed.
Honors & Awards
Forbes 30 Under 30 Scholar, Forbes (09/30/2019)
2018 Trainee Award, Wound Healing Society (05/30/2018)
Education & Certifications
Bachelor of Science, University of California, Davis, Biological Sciences (2009)
Mechanical Strain Drives Myeloid Cell Differentiation Toward Pro-Inflammatory Subpopulations.
Advances in wound care
OBJECTIVE: After injury, humans and other mammals heal by forming fibrotic scar tissue with diminished function, and this healing process involves the dynamic interplay between resident cells within the skin and cells recruited from the circulation. Recent studies have provided mounting evidence that external mechanical forces stimulate intracellular signaling pathways to drive fibrotic processes.INNOVATION: While most studies have focused on studying mechanotransduction in fibroblasts, recent data suggest that mechanical stimulation may also shape the behavior of immune cells, referred to as "mechano-immunomodulation". However, the effect of mechanical strain on myeloid cell recruitment and differentiation remains poorly understood and has never been investigated at the single cell level.APPROACH: In this study, we utilized a three-dimensional (3D) in vitro culture system that permits the precise manipulation of mechanical strain applied to cells. We cultured myeloid cells and used single cell RNA-sequencing to interrogate the effects of strain on myeloid differentiation and transcriptional programming.RESULTS: Our data indicate that myeloid cells are indeed mechanoresponsive, with mechanical stress influencing myeloid differentiation. Mechanical strain also upregulated a cascade of inflammatory chemokines, most notably from the Ccl family.CONCLUSION: Further understanding of how mechanical stress affects myeloid cells in conjunction with other cell types in the complicated, multicellular milieu of wound healing may lead to novel insights and therapies for the treatment of fibrosis.
View details for DOI 10.1089/wound.2021.0036
View details for PubMedID 34278820
Mechanical Activation Of Inflammation At The Implant-tissue Interface Underlies Pathological Foreign Body Response
WILEY. 2021: A9
View details for Web of Science ID 000650720500032
CRISPR/Cas9 Editing Of Autologous Dendritic Cells To Enhance Angiogenesis And Wound Healing
WILEY. 2021: A31-A32
View details for Web of Science ID 000650720500079
Disrupting Mechanotransduction Reduces Scar Formation And Restores Cellular Subpopulations In A Large Animal Model Of Skin Grafting
WILEY. 2021: A12-A13
View details for Web of Science ID 000650720500039
Adipose-derived stromal cells seeded in pullulan-collagen hydrogels improve healing in murine burns.
Tissue engineering. Part A
Burn scars and scar contractures cause significant morbidity for patients. Recently, cell-based therapies have been proposed as an option for improving healing and reducing scarring after burn injury, through their known pro-angiogenic and immunomodulatory paracrine effects. Our lab has developed a pullulan-collagen hydrogel that, when seeded with mesenchymal stem cells (MSCs), improves cell viability and augments their pro-angiogenic capacity in vivo. Concurrently, recent research suggests that prospective isolation of cell subpopulations with desirable transcriptional profiles can be used to further improve cell-based therapies. In this study, we examined whether adipose-derived stem cell-seeded hydrogels could improve wound healing following thermal injury using a murine contact burn model. Partial thickness contact burns were created on the dorsum of mice. On days 5 and 10 following injury, burns were debrided and received either ASC-hydrogel, ASC injection alone, hydrogel alone, or no treatment. On days 10 and 25, burns were harvested for histologic and molecular analysis. This experiment was repeated using CD26+/CD55+ FACS-enriched ASCs to further evaluate the regenerative potential of ASCs in wound healing. ASC-hydrogel-treated burns demonstrated accelerated time to re-epithelialization, greater vascularity, and increased expression of the pro-angiogenic genes MCP-1, VEGF, and SDF-1 at both the mRNA and protein level. Expression of the pro-fibrotic gene Timp1 and pro-inflammatory gene Tnfa were down-regulated in ASC-hydrogel treated burns. ASC-hydrogel treated burns exhibited reduced scar area compared to hydrogel-treated and control wounds, with equivalent scar density. CD26+/CD55+ ASC-hydrogel treatment resulted in accelerated healing, increased dermal appendage count, and improved scar quality with a more reticular collagen pattern. Here we find that ASC-hydrogel therapy is effective for treating burns, with demonstrated pro-angiogenic, fibro-modulatory and immunomodulatory effects. Enrichment for CD26+/CD55+ ASCs has additive benefits for tissue architecture and collagen remodeling post-burn injury. Research is ongoing to further facilitate clinical translation of this promising therapeutic approach.
View details for DOI 10.1089/ten.TEA.2020.0320
View details for PubMedID 33789446
Disrupting biological sensors of force promotes tissue regeneration in large organisms.
2021; 12 (1): 5256
Tissue repair and healing remain among the most complicated processes that occur during postnatal life. Humans and other large organisms heal by forming fibrotic scar tissue with diminished function, while smaller organisms respond with scarless tissue regeneration and functional restoration. Well-established scaling principles reveal that organism size exponentially correlates with peak tissue forces during movement, and evolutionary responses have compensated by strengthening organ-level mechanical properties. How these adaptations may affect tissue injury has not been previously examined in large animals and humans. Here, we show that blocking mechanotransduction signaling through the focal adhesion kinase pathway in large animals significantly accelerates wound healing and enhances regeneration of skin with secondary structures such as hair follicles. In human cells, we demonstrate that mechanical forces shift fibroblasts toward pro-fibrotic phenotypes driven by ERK-YAP activation, leading to myofibroblast differentiation and excessive collagen production. Disruption of mechanical signaling specifically abrogates these responses and instead promotes regenerative fibroblast clusters characterized by AKT-EGR1.
View details for DOI 10.1038/s41467-021-25410-z
View details for PubMedID 34489407
Hydrogel Scaffolds to Deliver Cell Therapies for Wound Healing.
Frontiers in bioengineering and biotechnology
2021; 9: 660145
Cutaneous wounds are a growing global health burden as a result of an aging population coupled with increasing incidence of diabetes, obesity, and cancer. Cell-based approaches have been used to treat wounds due to their secretory, immunomodulatory, and regenerative effects, and recent studies have highlighted that delivery of stem cells may provide the most benefits. Delivering these cells to wounds with direct injection has been associated with low viability, transient retention, and overall poor efficacy. The use of bioactive scaffolds provides a promising method to improve cell therapy delivery. Specifically, hydrogels provide a physiologic microenvironment for transplanted cells, including mechanical support and protection from native immune cells, and cell-hydrogel interactions may be tailored based on specific tissue properties. In this review, we describe the current and future directions of various cell therapies and usage of hydrogels to deliver these cells for wound healing applications.
View details for DOI 10.3389/fbioe.2021.660145
View details for PubMedID 34012956
Flexible smart bandage for wireless wound healing
WILEY. 2020: S24
View details for Web of Science ID 000548418300050
Cryopreserved human skin allografts promote angiogenesis and dermal regeneration in a murine model.
International wound journal
Cryopreserved human skin allografts (CHSAs) are used for the coverage of major burns when donor sites for autografts are insufficiently available and have clinically shown beneficial effects on chronic non-healing wounds. However, the biologic mechanisms behind the regenerative properties of CHSA remain elusive. Furthermore, the impact of cryopreservation on the immunogenicity of CHSA has not been thoroughly investigated and raised concerns with regard to their clinical application. To investigate the importance and fate of living cells, we compared cryopreserved CHSA with human acellular dermal matrix (ADM) grafts in which living cells had been removed by chemical processing. Both grafts were subcutaneously implanted into C57BL/6 mice and explanted after 1, 3, 7, and 28 days (n = 5 per group). A sham surgery where no graft was implanted served as a control. Transmission electron microscopy (TEM) and flow cytometry were used to characterise the ultrastructure and cells within CHSA before implantation. Immunofluorescent staining of tissue sections was used to determine the immune reaction against the implanted grafts, the rate of apoptotic cells, and vascularisation as well as collagen content of the overlaying murine dermis. Digital quantification of collagen fibre alignment on tissue sections was used to quantify the degree of fibrosis within the murine dermis. A substantial population of live human cells with intact organelles was identified in CHSA prior to implantation. Subcutaneous pockets with implanted xenografts or ADMs healed without clinically apparent rejection and with a similar cellular immune response. CHSA implantation largely preserved the cellularity of the overlying murine dermis, whereas ADM was associated with a significantly higher rate of cellular apoptosis, identified by cleaved caspase-3 staining, and a stronger dendritic cell infiltration of the murine dermis. CHSA was found to induce a local angiogenic response, leading to significantly more vascularisation of the murine dermis compared with ADM and sham surgery on day 7. By day 28, aggregate collagen-1 content within the murine dermis was greater following CHSA implantation compared with ADM. Collagen fibre alignment of the murine dermis, correlating with the degree of fibrosis, was significantly greater in the ADM group, whereas CHSA maintained the characteristic basket weave pattern of the native murine dermis. Our data indicate that CHSAs promote angiogenesis and collagen-1 production without eliciting a significant fibrotic response in a xenograft model. These findings may provide insight into the beneficial effects clinically observed after treatment of chronic wounds and burns with CHSA.
View details for DOI 10.1111/iwj.13349
View details for PubMedID 32227459
BIOMIMETIC ADIPIOSE STEM CELL DRESSING FOR SKIN REGENERATION
WILEY. 2019: A4
View details for Web of Science ID 000463117000011
ACCELERATION OF WOUND HEALING WITH PHD2-AND MIR210-TARGETING OLIGONUCLEOTIDES
WILEY. 2019: A36
View details for Web of Science ID 000463117000158
TOPICAL FOCAL ADHESION KINASE INHIBITOR PROMOTES SKIN REGENERATION AND SCAR PREVENTION IN A PRECLINICAL PORCINE MODEL
WILEY. 2019: A11–A12
View details for Web of Science ID 000463117000043
Optimization of transdermal deferoxamine leads to enhanced efficacy in healing skin wounds.
Journal of controlled release : official journal of the Controlled Release Society
Chronic wounds remain a significant burden to both the healthcare system and individual patients, indicating an urgent need for new interventions. Deferoxamine (DFO), an iron-chelating agent clinically used to treat iron toxicity, has been shown to reduce oxidative stress and increase hypoxia-inducible factor-1 alpha (HIF-1α) activation, thereby promoting neovascularization and enhancing regeneration in chronic wounds. However due to its short half-life and adverse side effects associated with systemic absorption, there is a pressing need for targeted DFO delivery. We recently published a preclinical proof of concept drug delivery system (TDDS) which showed that transdermally applied DFO is effective in improving chronic wound healing. Here we present an enhanced TDDS (eTDDS) comprised exclusively of FDA-compliant constituents to optimize drug release and expedite clinical translation. We evaluate the eTDDS to the original TDDS and compare this with other commonly used delivery methods including DFO drip-on and polymer spray applications. The eTDDS displayed excellent physicochemical characteristics and markedly improved DFO delivery into human skin when compared to other topical application techniques. We demonstrate an accelerated wound healing response with the eTDDS treatment resulting in significantly increased wound vascularity, dermal thickness, collagen deposition and tensile strength. Together, these findings highlight the immediate clinical potential of DFO eTDDS to treating diabetic wounds. Further, the topical drug delivery platform has important implications for targeted pharmacologic therapy of a wide range of cutaneous diseases.
View details for DOI 10.1016/j.jconrel.2019.07.009
View details for PubMedID 31299261
- Controlled Delivery of a Focal Adhesion Kinase Inhibitor Results in Accelerated Wound Closure with Decreased Scar Formation JOURNAL OF INVESTIGATIVE DERMATOLOGY 2018; 138 (11): 2452–60
Deferoxamine Can Prevent Pressure Ulcers and Accelerate Healing in Aged Mice.
Wound repair and regeneration : official publication of the Wound Healing Society [and] the European Tissue Repair Society
Chronic wounds are a significant medical and economic problem worldwide. Individuals over the age of 65 are particularly vulnerable to pressure ulcers and impaired wound healing. With this demographic growing rapidly there is a need for effective treatments. We have previously shown that defective hypoxia signaling through destabilization of the master hypoxia-inducible factor 1alpha (HIF-1alpha) underlies impairments in both aging and diabetic wound healing. To stabilize HIF-1alpha, we developed a transdermal delivery system of the FDA-approved small molecule deferoxamine (DFO) and found that transdermal DFO could both prevent and treat ulcers in diabetic mice. Here, we show that transdermal DFO can similarly prevent pressure ulcers and normalize aged wound healing. Enhanced wound healing by DFO is brought about by stabilization of HIF-1alpha and improvements in neovascularization. Transdermal DFO can be rapidly translated into the clinic and may represent a new approach to prevent and treat pressure ulcers in aged patients. This article is protected by copyright. All rights reserved.
View details for PubMedID 30152571
RNA-Based Combination Therapy for Diabetic Wound Healing
CELL PRESS. 2018: 38–39
View details for Web of Science ID 000435342200078
- Deferoxamine can prevent pressure ulcers and accelerate healing in aged mice WOUND REPAIR AND REGENERATION 2018; 26 (3): 300–305
Controlled Delivery of a Focal Adhesion Kinase Inhibitor Results in Accelerated Wound Closure with Decreased Scar Formation.
The Journal of investigative dermatology
Formation of scars following wounding or trauma represents a significant healthcare burden costing the economy billions of dollars every year. Activation of focal adhesion kinase (FAK) has been shown to play a pivotal role in transducing mechanical signals to elicit fibrotic responses and scar formation during wound repair. We have previously shown that inhibition of FAK using local injections of a small molecule FAK inhibitor (FAKI) can attenuate scar development in a hypertrophic scar model. Clinical translation of FAKI therapy has been challenging, however, due to the lack of an effective drug delivery system for extensive burn injuries, blast injuries, and large excisional injuries. To address this issue, we have developed a pullulan collagen-based hydrogel to deliver FAKI to excisional and burn wounds in mice. Specifically, two distinct drug-laden hydrogels were developed for rapid or sustained release of FAKI for treatment of burn wounds and excisional wounds, respectively. Controlled delivery of FAKI via pullulan collagen hydrogels accelerated wound healing, reduced collagen deposition and activation of scar forming myofibroblasts in both wound healing models. Our study highlights a biomaterial-based drug delivery approach for wound and scar management that has significant translational implications.
View details for PubMedID 29775632
Acceleration of Diabetic Wound Healing with PHD2- and miR-210-targeting Oligonucleotides.
Tissue engineering. Part A
View details for PubMedID 29644938
Allogeneic Cd26/Cd55 Cell Therapy for Treating Burn Wounds
WILEY. 2018: A9
View details for Web of Science ID 000430308600032
Transdermal Deferoxamine Enhances Wound Healing in Aged Mice
WILEY. 2018: A10
View details for Web of Science ID 000430308600036
Identification of cancer stem cell subpopulations of CD34(+) PLC/PRF/5 that result in three types of human liver carcinomas.
Stem cells and development
2015; 24 (8): 1008-1021
CD34(+) stem cells play an important role during liver development and regeneration. Thus, we hypothesized that some human liver carcinomas (HLCs) might be derived from transformed CD34(+) stem cells. Here, we determined that a population of CD34(+) cells isolated from PLC/PRF/5 hepatoma cells (PLC) appears to function as liver cancer stem cells (LCSCs) by forming HLCs in immunodeficient mice with as few as 100 cells. Moreover, the CD34(+) PLC subpopulation cells had an advantage over CD34(-) PLCs at initiating tumors. Three types of HLCs were generated from CD34(+) PLC: hepatocellular carcinomas (HCCs); cholangiocarcinomas (CC); and combined hepatocellular cholangiocarcinomas (CHCs). Tumors formed in mice transplanted with 12 subpopulations and 6 progeny subpopulations of CD34(+) PLC cells. Interestingly, progenies with certain surface antigens (CD133, CD44, CD90, or EPCAM) predominantly yielded HCCs. CD34(+) PLCs that also expressed OV6 and their progeny OV6(+) cells primarily produced CHC and CC. This represents the first experiment to demonstrate that the OV6(+) antigen is associated with human CHC and CC. CD34(+) PLCs that also expressed CD31 and their progeny CD31(+) cells formed CHCs. Gene expression patterns and tumor cell populations from all xenografts exhibited diverse patterns, indicating that tumor-initiating cells (TICs) with distinct antigenic profiles contribute to cancer cell heterogeneity. Therefore, we identified CD34(+) PLC cells functioning as LCSCs generating three types of HLCs. Eighteen subpopulations from one origin had the capacity independently to initiate tumors, thus functioning as TICs. This finding has broad implications for better understanding of the multistep model of tumor initiation and progression. Our finding also indicates that CD34(+) PLCs that also express OV6 or CD31 result in types of HLCs. This is the first report that PLC/PRF/5 subpopulations expressing CD34 in combination with particular antigens defines categories of HLCs, implicating a diversity of origins for HLC.
View details for DOI 10.1089/scd.2014.0405
View details for PubMedID 25519836
View details for PubMedCentralID PMC4390116
- Human liver carcinomas originated from CD34+ hematopoietic precursors Hepatology 2012: 56():807A–808A