Sensor-enabled Multilayer Artificial Intelligence Analysis for Predictive Wound Healing and Real-Time Patient Monitoring
WILEY. 2023: 268-269
View details for Web of Science ID 001005693800060
Wireless, closed-loop, smart bandage with integrated sensors and stimulators for advanced wound care and accelerated healing.
'Smart' bandages based on multimodal wearable devices could enable real-time physiological monitoring and active intervention to promote healing of chronic wounds. However, there has been limited development in incorporation of both sensors and stimulators for the current smart bandage technologies. Additionally, while adhesive electrodes are essential for robust signal transduction, detachment of existing adhesive dressings can lead to secondary damage to delicate wound tissues without switchable adhesion. Here we overcome these issues by developing a flexible bioelectronic system consisting of wirelessly powered, closed-loop sensing and stimulation circuits with skin-interfacing hydrogel electrodes capable of on-demand adhesion and detachment. In mice, we demonstrate that our wound care system can continuously monitor skin impedance and temperature and deliver electrical stimulation in response to the wound environment. Across preclinical wound models, the treatment group healed ~25% more rapidly and with ~50% enhancement in dermal remodeling compared with control. Further, we observed activation of proregenerative genes in monocyte and macrophage cell populations, which may enhance tissue regeneration, neovascularization and dermal recovery.
View details for DOI 10.1038/s41587-022-01528-3
View details for PubMedID 36424488
View details for PubMedCentralID 5350204
Aligned microribbon scaffolds with hydroxyapatite gradient for engineering bone-tendon interface.
Tissue engineering. Part A
Injuries of the bone-to-tendon interface, such as rotator cuff and anterior cruciate ligament tears, are prevalent yet effective methods for repair remain elusive. Tissue engineering approaches that use cells and biomaterials offer a promising potential solution for engineering the bone-tendon interface, but previous strategies require seeding multiple cell types and use of multiphasic scaffolds to achieve zonal-specific tissue phenotype. Furthermore, mimicking the aligned tissue morphology present in native bone-tendon interface in 3D remains challenging. To facilitate clinical translation, engineering bone-tendon interface using a single cell source and one continuous scaffold with alignment cues would be more attractive, but has not been achieved before. To address these unmet needs, here we develop an aligned gelatin-microribbon (muRB) hydrogel scaffold with hydroxyapatite nanoparticle (HA-np) gradient for guiding zonal-specific differentiation of human mesenchymal stem cell (hMSC) to mimic the bone-tendon interface. We demonstrate aligned muRBs led to cell alignment in 3D, and HA gradient induced zonal-specific differentiation of MSCs that resembles the transition at the bone-tendon interface. Short chrondrogenic priming prior to exposure to osteogenic factors further enhanced the mimicry of bone-cartilage-tendon transition with significantly improved tensile moduli of the resulting tissues. In summary, aligned gelatin muRBs with HA gradient coupled with optimized soluble factors may offer a promising strategy for engineering bone-tendon interface using a single cell source.
View details for DOI 10.1089/ten.TEA.2021.0099
View details for PubMedID 35229651
Galvanotactic Smart Bandage for Chronic Wound Management and Tissue Regeneration
WILEY. 2022: A36
View details for Web of Science ID 000763583000080
Inhibiting Fibroblast Mechanotransduction Modulates Severity of Idiopathic Pulmonary Fibrosis.
Advances in wound care
OBJECTIVE: Idiopathic pulmonary fibrosis (IPF) is a progressive fibrotic lung disease that affects 63 in every 100,000 Americans. Its etiology remains unknown, although inflammatory pathways appear to be important. Given the dynamic environment of the lung, we examined the significance of mechanotransduction on both inflammatory and fibrotic signaling during IPF.INNOVATION: Mechanotransduction pathways have not been thoroughly examined in the context of lung disease and pharmacologic approaches for IPF do not currently target these pathways. The interplay between mechanical strain and inflammation in pulmonary fibrosis remain incompletely understood.APPROACH: In this study, we used conditional KO mice to block mechanotransduction by knocking out FAK (Focal Adhesion Kinase) expression in fibroblasts, followed by induction of pulmonary fibrosis using bleomycin. We examined both normal human and human IPF fibroblasts and used immunohistochemistry, qRT-PCR, and Western Blot to evaluate the effects of FAK inhibition (FAKI) on modulating fibrotic and inflammatory genes.RESULTS: Our data indicate that deletion of FAK in mice reduces expression of fibrotic and inflammatory genes in lungs. Similarly, mechanical straining in normal human lung fibroblasts activates inflammatory and fibrotic pathways. FAK inhibition decreases these signals but has less effect on IPF fibroblasts as compared to normal human fibroblasts.CONCLUSION: Administering FAKI at early stages of fibrosis may attenuate the FAK-mediated fibrotic response pathway in IPF, potentially mediating disease progression.
View details for DOI 10.1089/wound.2021.0077
View details for PubMedID 34544267
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