RESUMO
Renal cell therapy has shown clinical efficacy in the treatment of acute renal failure (ARF) and promise for treatment of end-stage renal disease (ESRD) by supplementing conventional small solute clearance (hemodialysis or hemofiltration) with endocrine and metabolic function provided by cells maintained in an extracorporeal circuit. A major obstacle in the widespread adoption of this therapeutic approach is the lack of a cryopreservable system to enable distribution, storage, and therapeutic use at point of care facilities. This report details the design, fabrication, and assessment of a Bioartificial Renal Epithelial Cell System (BRECS), the first all-in-one culture vessel, cryostorage device, and cell therapy delivery system. The BRECS was loaded with up to 20 cell-seeded porous disks, which were maintained by perfusion culture. Once cells reached over 5 × 106 cells/disk for a total therapeutic dose of approximately 108 cells, the BRECS was cryopreserved for storage at -80°C or -140°C. The BRECS was rapidly thawed, and perfusion culture was resumed. Near precryopreservation values of cell viability, metabolic activity, and differentiated phenotype of functional renal cells were confirmed post-reconstitution. This technology could be extended to administer other cell-based therapies where metabolic, regulatory, or secretion functions can be leveraged in an immunoisolated extracorporeal circuit.
RESUMO
Herein, we report the synthesis and evaluation of a novel family of biodegradable and elastomeric polyesters, poly(diol citrates). Poly(diol citrates) were synthesized by reacting citric acid with various diols to form a covalent cross-linked network via a polycondensation reaction without using exogenous catalysts. The tensile strength of poly(diol citrates) were as high as 11.15+/-2.62 MPa and Young's modulus ranged from 1.60+/-0.05 to 13.98+/-3.05 MPa under the synthesis conditions that were investigated. Elongation was as high as 502+/-16%. No permanent deformation was found during mechanical tests. The equilibrium water-in-air contact angles of measured poly(diol citrates) films ranged from 15 degrees to 53 degrees . The mechanical properties, degradation and surface characteristics of poly(diol citrates) could be controlled by choosing different diols as well as by controlling the cross-link density of the polyester network. Various types of poly(diol citrate) scaffolds were fabricated to demonstrate their processing potential. These scaffolds were soft and could recover from deformation. In vitro and in vivo evaluation using cell culture and subcutaneous implantation, respectively, confirmed cell and tissue compatibility. The introduction of poly(diol citrates) will expand the repertoire of currently available biodegradable polymeric elastomers and should help meet the requirements of tissue engineering applications.