Development of poly(lactide-co-glycolide) scaffold-impregnated small intestinal submucosa with pores that stimulate extracellular matrix production in disc regeneration

The pore size and microstructure of scaffolds influences cell attachment, migration, proliferation and ingrowth, but the optimal pore size of scaffolds for disc tissue formation is not clearly understood. We developed porous poly(lactide-co-glycolide) (PLGA) scaffolds with various pore sizes for nucleus pulposus (NP) cell cultures and examined the effects of pore size on cell ingrowth and extracellular matrix (ECM) synthesis. High cell density in the small pores of scaffolds promotes collagen synthesis and cell migration through interconnected pores. Scaffolds with large pores exhibited slower cell proliferation and collagen synthesis. Guided by these results, we investigated a novel, biodegradable, synthetic/natural hybrid scaffold composed of PLGA and small intestinal submucosa (SIS) (PLGA-SIS) with the proper pore size for NP regeneration. We tested the morphological and physical properties of PLGA-SIS scaffolds and initial cell attachment and ECM production of NP in scaffolds. The mechanical and degradable properties of the PLGA-SIS scaffold were superior to those of SIS sponge and were similar to the properties of PLGA scaffold. NP cells grown on PLGA-SIS scaffold exhibited higher initial cell adhesion and ECM production than those grown on pure PLGA scaffold in a biological assay. In conclusion, this study suggests that a proper pore size of scaffolds is critical in NP regeneration, and that PLGA-SIS scaffolds with suitable pores might be useful as substrates for tissue-engineered biodiscs.