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

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 threedimensional 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.

Review of electrospun microtube array membrane (MTAM)‐a novel new class of hollow fiber for encapsulated cell therapy (ECT) in clinical applications

“…76 As described previously, a biodegradable material may be desirable for some applications where 2 and Figure 6). 74,76 Hence, in our previous works, we demonstrated the novel application of MTAMs as a culture substrate, which yields matured neuron-like cells, cultured from NSCs rapidly, which can be utilized for downstream research. 18,36,77 In the first example, the co-culture of the highest advanced neuronal properties (Figure 7C).…”

“…In a recent study, Nguyen and colleagues examined encapsulated cell retention and biocompatibility of MTAMs formed from PLGA with modified tube dimensions and pore sizes. 76 As described previously, a biodegradable material may be desirable for some applications where 2 and Figure 6). 74,76 Hence, in our previous works, we demonstrated the novel application of MTAMs as a culture substrate, which yields matured neuron-like cells, cultured from NSCs rapidly, which can be utilized for downstream research.…”

“…Data excerpted from. 74,76 number of animals needed for study, which is crucial for ethical and animal welfare reasons.…”

“…In a recent study, Nguyen and colleagues examined encapsulated cell retention and biocompatibility of MTAMs formed from PLGA with modified tube dimensions and pore sizes 76 . As described previously, a biodegradable material may be desirable for some applications where degradation of the material is a non‐invasive means of clearance.…”

“…Hematology and serum biochemistry showed only mild changes in white blood cells and inflammatory markers seven and 43 days after implantation (Table 2 and Figure 6). 74,76 As a comparison, MTAMs formed from PSF, with or without HDFs, were also implanted. Surprisingly, the PLGA‐based MTAM were found to retain more human donor cells than the non‐degradable PSF‐based MTAMs.…”