Chitosan–poly(lactide-co-glycolide) microsphere-based scaffolds for bone tissue engineering: In vitro degradation and in vivo bone regeneration studies
Received 16 December 2009; received in revised form 19 February 2010; accepted 17 March 2010. published online 22 March 2010.
Abstract
Natural polymer chitosan and synthetic polymer poly(lactide-co-glycolide) (PLAGA) have been investigated for a variety of tissue engineering applications. We have previously reported the fabrication and in vitro evaluation of a novel chitosan/PLAGA sintered microsphere scaffold for load-bearing bone tissue engineering applications. In this study, the in vitro degradation characteristics of the chitosan/PLAGA scaffold and the in vivo bone formation capacity of the chitosan/PLAGA-based scaffolds in a rabbit ulnar critical-sized-defect model were investigated. The chitosan/PLAGA scaffold showed slower degradation than the PLAGA scaffold in vitro. Although chitosan/PLAGA scaffold showed a gradual decrease in compressive properties during the 12-week degradation period, the compressive strength and compressive modulus remained in the range of human trabecular bone. Chitosan/PLAGA-based scaffolds were able to guide bone formation in a rabbit ulnar critical-sized-defect model. Microcomputed tomography analysis demonstrated that successful bridging of the critical-sized defect on the sides both adjacent to and away from the radius occurred using chitosan/PLAGA-based scaffolds. Immobilization of heparin and recombinant human bone morphogenetic protein-2 on the chitosan/PLAGA scaffold surface promoted early bone formation as evidenced by complete bridging of the defect along the radius and significantly enhanced mechanical properties when compared to the chitosan/PLAGA scaffold. Furthermore, histological analysis suggested that chitosan/PLAGA-based scaffolds supported normal bone formation via intramembranous formation.
aDepartment of Chemical Engineering, University of Virginia, Charlottesville, VA 22904, USA
bDepartment of Orthopaedic Surgery, University of Connecticut, Farmington, CT 06030, USA
cDepartment of Chemical, Materials and Biomolecular Engineering, University of Connecticut, Storrs, CT 06269, USA
dDepartment of Orthopaedic Surgery, University of Virginia, Charlottesville, VA 22908, USA
eDepartment of Biomedical Engineering, University of Virginia, Charlottesville, VA 22908, USA
fHospital for Special Surgery, New York, NY 10021, USA
gBiomaterials Department, National Research Centre, Cairo 12311, Egypt
Corresponding author at: The University of Connecticut, 263 Farmington Avenue, Farmington, CT 06032-3800, United States. Tel.: + 860 679 2594; fax: +1 860 679 1255.
ABSTRACT