Parametric studies of polycaprolactone-based composites for tissue engineering and regenerative medicine

Abstract

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 I would like to thank my supervisors Prof. Teoh Swee-Hin and Dr. Mark Chong for their supervision and guidance during the course of my study. Prof. Teoh has been instrumental in guiding my vision and maintaining my hunger and passion for research. He has been an inspiration to me ever since our association in my third year of undergraduate studies, through my FYP, Masters, and culminating in my PhD. I will never forget this phrase "Your mind must be like a parachute; It works best when open", one which is famous, and has guided the minds of many under him. Dr. Mark, whom I have known since my undergraduate days, has been simply one of the most dedicated and meticulous researchers I have met. He has undying passion for research, constantly seeking the scientific question. Through my time with him, I have matured much, and am looking forward to more exciting times ahead.