Development of 3D Printable Composites for Cranio-Maxillofacial Applications

The worldwide incidence of bone disorders has increased steeply in the past decade; in the craniofacial region specifically, congenital disorders, traumatic incidents and tumour removals are the major causes of bone loss. This has encouraged the emergence of bone tissue engineering substitutes as an alternative method to conventional bone grafts. However, the current approaches in the field face several limitations that has prevented the ultimate translation into clinical settings. In this project, a light curable methacrylate-based polymer, polypropylene glycol dimethacrylate (PPGDMA), was initially investigated for the purpose of reconstructing cranial defects. A mixture of monocalcium phosphate monohydrate and beta tri-calcium phosphate was incorporated in the polymer as the powder phase of choice. The experimental work involved optimisation of flowability of the polymer for 3D printing. Subsequently, the composite discs were fabricated by exposing 11 mm diameter discs to blue light; the rate of the monomer conversion was also determined upon photo-polymerisation with minimum of 62% conversion rate. Finally, the cytocompatibility of the composite discs was verified by seeding MC3T3 osteoprogenitor cells. The second part of this project involved the synthesis of a novel degradable polymer which was aimed at resorting maxillofacial deficiencies: ((((((((((((3R,3aR,6S,6aR)-hexahydrofuro[3,2-b]furan-3,6-diyl)bis(oxy))bis(ethane- 2,1 diyl))bis(oxy))bis(carbonyl))bis(azanediyl))bis(methylene))bis(3,3,5- trimethylcyclohexane-5,1-diyl))bis(azanediyl))bis(carbonyl))bis(oxy))bis(ethane- 2,1-diyl) bis(2-methylacrylate was referred to as CSMA-2. Nuclear Magnetic Resonance (NMR) analysis initially confirmed formation of this monomer. Stiffness was tested using a biaxial flexural test and the values were found to be 1.8-2.7 x 103 N.mm -2 in CSMA-2 and the composites. In vitro cell culture, using human bone marrow derived mesenchymal stem cells (BMSCs), confirmed non-toxicity of the samples. This was followed by in vivo assessment of CSMA-2 in a rat model; sign of neo-bone formation 8 weeks post implantation of CSMA-2 further verified noncytotoxicity of the polymer. Finally, Digital Light Processing (DLP) 3D printing allowed direct photo-polymerisation and setting of the bio ink into a mesh-like construct