Evaluation of small intestine submucosa and poly(caprolactone-co-lactide) conduits for peripheral nerve regeneration.

The present study employed nerve guidance conduits (NGCs) only, which were made of small intestine submucosa (SIS) and poly(caprolactone-co-lactide) (PCLA) to promote nerve regeneration in a peripheral nerve injury (PNI) model with nerve defects of 15 mm. The SIS- and PCLA-NGCs were easily prepared by rolling of a SIS sheet and a bioplotter using PCLA, respectively. The prepared SIS- and PCLA-NGCs fulfilled the general requirement for use as artificial peripheral NGCs such as easy fabrication, reproducibility for mass production, suturability, sterilizability, wettability, and proper mechanical properties to resist collapsing when applied to in vivo implantation. The SIS- and PCLA-NGCs appeared to be well integrated into the host sciatic nerve without causing dislocations and serious inflammation. All NGCs stably maintained their NGC shape for 8 weeks without collapsing, which matched well with the nerve regeneration rate. Staining of the NGCs in the longitudinal direction showed that the regenerated nerves grew successfully from the SIS- and PCLA-NGCs through the sciatic nerve-injured gap and connected from the proximal to distal direction along the NGC axis. SIS-NGCs exhibited a higher nerve regeneration rate than PCLA-NGCs. Collectively, our results indicate that SIS- and PCLA-NGCs induced nerve regeneration in a PNI model, a finding that has significant implications in the future with regard to the feasibility of clinical nerve regeneration with SIS- and PCLA-NGCs prepared through an easy fabrication method using promising biomaterials.

Preparation of three-dimensional scaffolds by using solid freeform fabrication and feasibility study of the scaffolds.

To adapt biomaterials for solid freeform fabrication (SFF), methoxy polyethylene glycol (MPEG)-(PLLA-co-PCL) (LxCy) block copolymers were prepared using MPEG as the initiator to precisely control the molecular weight of PLLA and PCL. The LxCy block copolymers were designed such that the PLLA and PCL content varied and their molecular weights were within 200-1000 kDa. The cylindrical LxCy scaffolds were prepared by using LxCy block copolymers in SFF. The feasibility of using LxCy block copolymers was examined in terms of flowability from the micronozzle and solidification at room temperature after scaffold printing. The flowability and solidification of LxCy block copolymers mainly depend on the proportions of PLLA and PCL. Fabrication of the cylindrical LxCy scaffolds by using SFF was rapid and showed high reproducibility. In in vivo implantation, the cylindrical LxCy scaffolds exhibited biocompatibility and gradual biodegradation on a 16 week timescale. Immunohistochemical characterization showed that the in vivo LxCy scaffolds elicit only a modest inflammatory response. Taken together, these results show that LxCy block copolymers may serve as suitable biomaterials for the fabrication of well-defined three-dimensional scaffolds by using SFF.

Injectable extracellular matrix hydrogel developed using porcine articular cartilage.

This work was first development of a delivery system capable of maintaining a sustained release of protein drugs at specific sites by using potentially biocompatible porcine articular cartilage. The prepared porcine articular cartilage powder (PCP) was easily soluble in phosphate-buffered saline. The PCP suspension easily entrapped bovine serum albumin-fluorescein isothiocyanate (BSA-FITC) in pharmaceutical formulations at room temperature. The aggregation of PCP and BSA-FITC was confirmed by dynamic light scattering. When the BSA-FITC-loaded PCP suspension was subcutaneously injected into rats, it gelled and formed an interconnecting three-dimensional PCP structure that allowed BSA to penetrate through it. The amount of BSA-FITC released from the PCP hydrogel was determined in rat plasma and monitored by real-time in vivo molecular imaging. The data indicated sustained release of BSA-FITC for 20 days in vivo. In addition, the PCP hydrogel induced a slight inflammatory response. In conclusion, we showed that the PCP hydrogel could serve as a minimally invasive therapeutics depot.