Parametric studies of polycaprolactone-based composites for tissue engineering and regenerative medicine
Date of Issue2014
School of Chemical and Biomedical Engineering
Bone is a composite structure that is made up of collagen (organic), calcium phosphates and trace metal elements (inorganic). Together with strict mechanical requirements, many scaffold-based tissue engineering strategies are now focused on developing composite systems that provide sufficient mechanical stability and biological stimulation to dictate osteogenic events in vivo. On this note, processing techniques for bioresorbable composites for bone tissue engineering have traditionally involved solvents and heat, which may not be ideal due to toxicity and material degradation, respectively. As such, alternative processing methods are actively pursued and evaluated. In this thesis, we hypothesized that cryomilling is a potential alternative processing technique for composites. The effectiveness of cyromilling to refine particle size was first demonstrated using PCL and PLGA. Strength improvement was demonstrated, particularly in the case of PLGA. By subjecting composite materials to temperatures sufficiently below glass transition, effective attrition into fine powders (micron-range) was achieved. In addition, this attrition process facilitated distribution of the fillers (tricalcium phosphate (TCP) and magnesium (Mg)), resulting in homogeneous PCL/TCP and PCL/Mg powders. This homogeneous distribution was retained in further postprocessing techniques. A mechanistic explanation for this phenomenon may be that of solid-state diffusion, where effective interfacial interactions are created, resulting in the retention of their homogeneous distributions. The implications of this phenomenon were demonstrated through a variety of in vitro studies, with notable advantages in composites processed with cryomilling (such as mechanical and biological responses). In vivo, PCL/TCP films were able to influence bone regeneration by preventing soft tissue invasion into the defect site (in pigs and rabbits). PCL/Mg films were also biocompatible, with no cases of rejection in pigs. When fabricated into 3D scaffolds with applications in cranioplasty, their biocompatibility with brain tissue was established in rat models. In conclusion, we have demonstrated in this thesis that cyromilling will be a suitable processing method that is entirely solvent-free, and maintains homogeneity of composites processed in this manner. This culminated in robust in vitro and in vivo responses as described. Going forwards, we believe that cryomilling may become clinically translatable. At the same time, we aim to develop cryomilling as a versatile platform for the incorporation of drugs, antibiotics, and growth factors.