Induction of adipose-derived stem cells on injectable nanofibrous spongy microspheres for vascularized adipose tissue regeneration in vivo

Abstract

Event Abstract Back to Event Induction of adipose-derived stem cells on injectable nanofibrous spongy microspheres for vascularized adipose tissue regeneration in vivo Yasmine Doleyres1, Xiaobing Jin2 and Peter X. Ma1, 2, 3, 4 1 University of Michigan, Macromolecular Science and Engineering Program, United States 2 University of Michigan, Department of Biologic and Materials Sciences, United States 3 University of Michigan, Department of Biomedical Engineering, United States 4 University of Michigan, Department of Materials Science and Engineering, United States Soft tissue defects in the craniofacial region or the breast region often occur due to congenital defects, traumatic injury, or cancer occurring in the underlying tissue[1]. Correcting these defects in the case of facial reconstruction can be done by transplanting adipose (fat) tissue from another area of the body into the facial region or in the case of reconstruction following breast cancer can be done through autologous tissue transplantation, if available, or using silicone or saline-filled implants. The problem with these options is that between 20-90% of transplanted fat tissue often resorbs within a couple months after being transplanted due to lack of vascularization and implants often fail because of capsular constriction and become infected, leading to multiple surgeries in both cases[1]-[8]. The most ideal option would be to regenerate one’s own adipose tissue just as it is naturally produced by the body. Lasting tissue regeneration options for in vivo adipose tissue have yet to be developed, and this is the goal of this project. Novel nanofibrous spongy (porous) microspheres (NF-SMS) have been developed and appear to be a suitable scaffolding or cell-carrying material for the differentiation and growth of adipose-derived stem cells (ASCs). These microspheres made of poly-L-lactic acid (PLLA) have a nanofibrous architecture that well-mimics the cells’ natural extracellular matrix and also allows for cells to pack the interior of the microspheres[9]. A high number of cells are able to pack into the interior of the microspheres and the high cell attachment on the microspheres is critical for adipose tissue regeneration as high cell-cell contact is necessary for tissue growth. Adipogenesis of the isolated ASCs is induced for 3-4 days in growth medium containing Dexamethasone, Indomethacin, and 3-isobuytl-1-methylxanthine (IBMX)[10],[11]. The cells are then combined with the microspheres for a few hours and subsequently injected subcutaneously in a nude mouse model for testing. Early in vitro experiments comparing the growth and differentiation of the cells on the NF-SMS against enclosed nanofibrous hollow microspheres as a control show increased cell attachment and integration on the NF-SMS. The cells on the NF-SMS also showed greater Nile Red lipid staining and overall positive results in vitro. Current in vivo experiments are being done and are incorporating poly(lactic-co-glycolic acid) (PLGA) nanoparticles loaded with insulin for sustained released of insulin from these particles during the early period of growth (1-2 weeks). Insulin appears to be very critical in the adipogenesis pathway and should be crucial in helping to produce substantial tissue in vivo[12]-[14]. These PLGA nanoparticles are injected along with the microsphere-cell complexes. Having a patient regenerate adipose tissue from their own pre-adipocyte cells will be advantageous because it eliminates the need for something foreign in the body and multiple invasive surgeries. Ensuring that the adipose tissue produced does not resorb as is the case in previous research attempts would be done by functionalizing the microsphere scaffolds with an angiogenic factor, which is the next goal of this project.