Degradable Biocompatible Porous Microtube Scaffold for Extended Donor Cell Survival and Activity

Cell therapy has significant therapeutic potential but is often 6 limited by poor donor cell retention and viability at the host implantation site. 7 Biomaterials can improve cell retention by providing cells with increased cell−cell 8 and cell−matrix contacts and materials that allow three-dimensional cell culture 9 to better recapitulate native cell morphology and function. In this study, we 10 engineered a scaffold that allows for cell encapsulation and sustained three11 dimensional cell culture. Since cell therapy is largely driven by paracrine 12 secretions, the material was fabricated by electrospinning to have a large internal 13 surface area, micrometer-thin walls, and nanoscale surface pores to allow for 14 nutrient exchange without early cell permeation. The material is degradable, 15 which allows for less invasive removal of the implant. In this study, a 16 biodegradable poly(lactic-co-glycolic acid) (PLGA) microtube array membrane 17 was fabricated. In vitro testing showed that the material supported the culture of human dermal fibroblasts for at least 21 days, with 18 paracrine secretion of pro-angiogenic FGF2. In vivo xenotransplantation of human cells in an immunocompetent mouse showed that 19 donor cells could be maintained for more than one month and the material showed no obvious toxicity. Analysis of gene expression 20 and tissue histology surrounding the implant showed that the material produced muted inflammatory and immune responses 21 compared to a permanent implant and increased markers of angiogenesis.