ORCID Profile
0000-0002-2748-774X
Current Organisation
Universidade Federal do Rio de Janeiro
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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: Wiley
Date: 29-06-2020
Publisher: MDPI AG
Date: 30-07-2021
Abstract: Impaired skin wound healing due to severe injury often leads to dysfunctional scar tissue formation as a result of excessive and persistent myofibroblast activation, characterised by the increased expression of α-smooth muscle actin (αSMA) and extracellular matrix (ECM) proteins. Yet, despite extensive research on impaired wound healing and the advancement in tissue-engineered skin substitutes, scar formation remains a significant clinical challenge. This study aimed to first investigate the effect of methacrylate gelatin (GelMA) biomaterial stiffness on human dermal fibroblast behaviour in order to then design a range of 3D-printed GelMA scaffolds with tuneable structural and mechanical properties and understand whether the introduction of pores and porosity would support fibroblast activity, while inhibiting myofibroblast-related gene and protein expression. Results demonstrated that increasing GelMA stiffness promotes myofibroblast activation through increased fibrosis-related gene and protein expression. However, the introduction of a porous architecture by 3D printing facilitated healthy fibroblast activity, while inhibiting myofibroblast activation. A significant reduction was observed in the gene and protein production of αSMA and the expression of ECM-related proteins, including fibronectin I and collagen III, across the range of porous 3D-printed GelMA scaffolds. These results show that the 3D-printed GelMA scaffolds have the potential to improve dermal skin healing, whilst inhibiting fibrosis and scar formation, therefore potentially offering a new treatment for skin repair.
Publisher: Frontiers Media SA
Date: 03-12-2019
Location: Brazil
Location: Brazil
No related grants have been discovered for Ronaldo do Amaral.