ORCID Profile
0000-0002-4809-2034
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Publisher: Wiley
Date: 14-09-2022
Abstract: Diabetic foot ulcers (DFUs) are chronic wounds sustained by pathological fibroblasts and aberrant extracellular matrix (ECM). Porous collagen‐based scaffolds (CS) have shown clinical promise for treating DFUs but may benefit from functional enhancements. Our previous work showed fibroblasts differentiated from induced pluripotent stem cells are an effective source of new ECM mimicking fetal matrix, which notably promotes scar‐free healing. Likewise, functionalizing CS with this rejuvenated ECM shows potential for DFU healing. Herein, an approach to DFU healing is demonstrated for the first time using biopsied cells from DFU patients, reprogramming those cells, and functionalizing CS with patient‐specific ECM as a personalized acellular tissue‐engineered scaffold. A two‐pronged approach is taken: 1) direct ECM blending into scaffold fabrication, and 2) seeding scaffolds with reprogrammed fibroblasts for ECM deposition followed by decellularization. The decellularization approach reduces cell number requirements and maintains naturally deposited ECM proteins. Both approaches show enhanced ECM deposition from DFU fibroblasts. Decellularized scaffolds additionally enhance glycosaminoglycan deposition and subsequent vascularization. Finally, reprogrammed ECM scaffolds from patient‐matched DFU fibroblasts outperform those from healthy fibroblasts in several metrics, suggesting ECM is in fact able to redirect resident pathological fibroblasts in DFUs toward healing, and a patient‐specific ECM signature may be beneficial.
Publisher: Elsevier BV
Date: 02-2021
Publisher: The Company of Biologists
Date: 2018
DOI: 10.1242/BIO.027060
Abstract: Therapeutic induction of blood vessel growth (angiogenesis) in ischemic tissues holds great potential for treatment of myocardial infarction and stroke. Achieving sustained angiogenesis and vascular maturation has, however, been highly challenging. Here we demonstrate that collagen:alginate hydrogels containing therapeutic, pro-angiogenic FGF-2, and formulated as microspheres, is a promising and clinically relevant vehicle for therapeutic angiogenesis. By titrating the amount of readily dissolvable and degradable collagen with more slowly degradable alginate in the hydrogel mixture, the degradation rates of the biomaterial controlling the release kinetics of embedded pro-angiogenic FGF-2 can be adjusted. Furthermore, we elaborate a microsphere synthesis protocol allowing accurate control over sphere size, also a critical determinant of degradation/release rate. As expected, alginate:collagen microspheres were completely biocompatible and did not cause any adverse reactions when injected in mice. Importantly, the amount of pro-angiogenic FGF-2 released from such microspheres led to robust induction of angiogenesis in zebrafish embryos similar to that achieved by injecting FGF-2-releasing cells. These findings highlight the use of microspheres constructed from collagen:alginate hydrogels as a promising and clinically relevant delivery system for pro-angiogenic therapy.
Publisher: Elsevier BV
Date: 09-2020
Publisher: Elsevier BV
Date: 11-2016
No related grants have been discovered for Mark Lemoine.