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