Biodegradable Chitosan-graft-Poly(l-lactide) Copolymers For Bone Tissue Engineering.

Maria Kaliva,Dimitrios A Dragatogiannis,Anthie Georgopoulou,Maria Chatzinikolaidou,Maria Vamvakaki,Costas A Charitidis

doi:10.3390/polym12020316

Abstract

The design and synthesis of new biomaterials with adjustable physicochemical and biological properties for tissue engineering applications have attracted great interest. In this work, chitosan-graft-poly(l-lactide) (CS-g-PLLA) copolymers were prepared by chemically binding poly(l-lactide) (PLLA) chains along chitosan (CS) via the “grafting to” approach to obtain hybrid biomaterials that present enhanced mechanical stability, due to the presence of PLLA, and high bioactivity, conferred by CS. Two graft copolymers were prepared, CS-g-PLLA(80/20) and CS-g-PLLA(50/50), containing 82 wt % and 55 wt % CS, respectively. Degradation studies of compressed discs of the copolymers showed that the degradation rate increased with the CS content of the copolymer. Nanomechanical studies in the dry state indicated that the copolymer with the higher CS content had larger Young modulus, reduced modulus and hardness values, whereas the moduli and hardness decreased rapidly following immersion of the copolymer discs in alpha-MEM cell culture medium for 24 h. Finally, the bioactivity of the hybrid copolymers was evaluated in the adhesion and growth of MC3T3-E1 pre-osteoblastic cells. In vitro studies showed that MC3T3-E1 cells exhibited strong adhesion on both CS-g-PLLA graft copolymer films from the first day in cell culture, whereas the copolymer with the higher PLLA content, CS-g-PLLA(50/50), supported higher cell growth.

Highlights

Despite the intrinsic ability of small bone defects to heal spontaneously with minimal cure, the treatment of large bone defects, resulting from trauma or disease, still remains a big challenge in orthopedics, with limited success until recently, due to the complicated structure of bone [1,2,3]
The degree of polymerization (DP) of PLLA-COOH was calculated by rationing the integrals of the peaks attributed to the Hd and Hc protons of the polymer, and was found to be DP = 119, which corresponds to a molecular weight of Mn = 8600 g/mol, in good agreement with the gel-permeation chromatography (GPC) results, given the difference in the hydrodynamic volume of PLLA-COOH
The chemical structure and copolymer composition were investigated by 1 H NMR and Fourier-transform infrared (FTIR) spectroscopies, which verified the successful synthesis of the graft copolymers

Summary

Introduction

Despite the intrinsic ability of small bone defects to heal spontaneously with minimal cure, the treatment of large bone defects, resulting from trauma or disease, still remains a big challenge in orthopedics, with limited success until recently, due to the complicated structure of bone [1,2,3]. Tissue engineering has emerged as a promising therapeutic approach for the restoration of the function of damaged or diseased skeletal tissue. It is based on a multi-component system that combines cells, bioactive molecules and porous three-dimensional (3D) scaffolds, composed of biodegradable biomaterials, aiming to stimulate the inherent ability of bone to regenerate by promoting osteogenesis, osteoconductivity and osseointegration [2,4,5]. Biomaterials for use in tissue engineering should be biocompatible and bioactive, as well as present controllable biodegradability and appropriate mechanical properties, and they should be able to form structural scaffolds and promote regenerative processes via the effective delivery of bioactive cues [1,2,5]. PLA has been approved by Food and Drug Administration (FDA) for clinical use [14,15]

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Discussion

Conclusion