(554g) Integrated Effects of Matrix Mechanics and Sustained Release of Bioactive Factors on Accelerating Wound Healing

Dynamic interactions between extracellular matrix (ECM), growth factors, and various cells types are integral to wound healing process. However, dysregulation of reparative process, due to systemic abnormalities such as diabetes results in chronic (non-healing or hard-to heal) wounds. The gradual comprehension of the role of mesenchymal stem cells (MSC) in various phases of wound healing has prompted development of MSC-based therapy for hard-to heal wounds. However, the low engraftment and retention rate of MSCs at the wound site limit the clinical translation of cellular therapy. Mounting evidence corroborates that the pre-dominant mechanisms by which MSCs participate in wound healing and functional recovery of tissue are likely mediated by paracrine effect of secreted bioactive factors (diverse array of biomolecules, including cytokines, chemokines, angiogenic factors, growth factors, extracellular matrix proteases, and hormones, known as “secretome”) rather than cell replacement effect.

In this study, we investigated the integrated effects of matrix stiffening and MSC secretome on behaviors of fibroblasts. Our study revealed that increase in matrix stiffness enhanced the proliferation of fibroblasts. We also investigated the effect of MSC conditioned medium on the migratory and proliferative activity of dermal fibroblasts. For the purpose, MSCs were cultured in 6-well plates till they reach 80% confluency. The culture medium was then replaced with serum-free DMEM and cultured for 48h. The spent media was then collected and centrifuged to remove the cell debris. Fibroblasts were cultured in the presence of conditioned medium, normal culture media (positive control) and serum-free DMEM (negative control). Our study revealed that the presence of conditioned medium enhanced migration and proliferation fibroblasts. During the presentation, influence of sustained release of conditioned medium on the function of fibroblasts seeded on gels of optimized stiffness will be discussed.