A novel bicomponent, hydrogel-bored, biodegradable polymer fiber for tissue engineering and drug delivery applications

We have developed a novel biodegradable, polymeric fiber construct that is co-extruded using a wet-spinning process into a core-sheath format with a polysaccharide pre-hydrogel solution as a core fluid. The properties of the gel and the polymer can be modified extensively, resulting in numerous fiber formats that provide a variety of profiles for release of loaded proteins, growth factors, drugs, and other therapeutics. These biologically sensitive agents are protected from denaturation by either their incorporation into the hydrogel, their incorporation as a dispersed phase into a polymeric continuous phase emulsion extruded as the fiber sheath, or through combinations thereof. Multiple agents can be co-loaded in this manner, resulting in a variety of biologically active therapeutic capabilities.; We show that this core-sheath fiber format will load a model protein that can be delivered for extended periods in vitro. The biodegradable, biocompatible fibers were extruded from polymeric emulsions comprised of solutions of various molecular weights of poly(L-lactic acid) (PLLA) dissolved in chloroform and containing dispersed, protein-free aqueous phases comprising up to 10% of the emulsion volume. Bovine serum albumin (BSA) was loaded into the fiber core. The greater the volume of the protein-free aqueous phase dispersed into the polymeric continuous phase emulsion, the greater the total release of BSA encapsulated by a core gel comprised of 1% sodium alginate solution.; Modifications to the gel and fiber compositions enabled us to deliver, over a period of 25 days, biologically active nerve growth factor (NGF) from this core-sheath format into serum-free media supplemented with BSA. The biological activity of the NGF was quantitatively verified through a PC12 cell-based survivability assay using the agent alamarBlue(TM). Additional qualitative verification of the NGF bioactivity occurred through exposure of PC12 cells in culture to supernatants from the release studies and to co-cultured fibers. ELISA verified detectable concentrations of NGF in solution throughout a period of 30 days.; We conclude this fiber format provides a promising vehicle for in vivo delivery of biologically sensitive molecules. Its biocompatibility and biodegradability also allow for its use as a possible substrate for tissue engineering applications.