Hybrid Chitosan/PCL Shape Memory Scaffolds with Potential for Bone Regeneration and Infection Resistance

We have previously developed a regenerative engineering approach to repair irregularly shaped craniomaxillofacial bone defects utilizing "self-fitting" shape memory polymer (SMP) scaffolds based on cross-linked poly(ε-caprolactone) (PCL). However, a slow rate of degradation may hinder neotissue infiltration, and a lack of innate antimicrobial activity creates vulnerability to postoperative infection stemming from biofilm formation. Introduction of chitosan (CS), a hydrophilic natural polymer with known antimicrobial behavior, to PCL SMP scaffolds could provide a synergistic combination of desirable properties. Herein, for the first time, we report the development of hybrid (i.e., formed from a synthetic and a naturally derived polymer) CS/PCL SMP scaffolds. A series of eight highly porous PCL/CS-graft-PCL scaffolds were formed as semi-interpenetrating networks (semi-IPNs) using cross-linkable PCL-diacrylate (PCL-DA) and thermoplastic CS-graft-PCL copolymers. Scaffold CS content was tuned by graft copolymer composition and wt % ratio to PCL-DA. A solvent-cast particulate leaching process produced scaffolds with highly interconnected macropores (∼240 μm), which is conducive to osteogenesis. Owing to sufficient retention of PCL crystallinity, all hybrid scaffolds retained excellent shape memory and robust mechanical behavior. Compared with PCL scaffold controls, hybrid scaffolds of sufficient CS content exhibited faster rates of in vitro degradation, which is favorable to osteoinductivity. Accelerated degradation was related to increased hydrophilicity and phase separation effects. Hybrid scaffolds also displayed an ability to reduce C. albicans biofilm formation by both direct and indirect contact, compared with PCL scaffolds.