Aliphatic polycarbonates: building blocks for new biodegradable biomaterials

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This proposal concerns the development of advanced and innovative polymers for load-bearing, soft tissue regeneration and sustained and controllable drug delivery. The majority of hydrophobic biodegradable polymers designed for these purposes are prepared using aliphatic polyesters such as poly(lactide-co-glycolide)s. While these polymers are degradable in vivo via hydrolysis, the acidic products formed elicit undesirable inflammation in the local tissue, cause local cell death, and can degrade incorporated acid-sensitive drugs. Aliphatic polycarbonates, by contrast, are hydrolysis resistant yet biodegrade in a molecular weight-dependent manner through the action of enzymes secreted by host cells. Importantly, their degradation does not result in acidic products and as a result they feature low cytotoxicity. The research program proposed will build on our previous work in two areas: 1) aliphatic polycarbonates with readily adjustable degradation rates for peptide/protein delivery and 2) thermally stable but photo-cross-linkable copolymers for additive manufacturing of strong and creep resistant scaffolds for tendon tissue engineering. In the drug delivery focus of the research program, two different approaches will be pursued. In the first, peptide loaded microspheres and injectable liquid formulations will be developed for long-term sustained release. Our new polymer strategy for these objectives has been designed to overcome complications with respect to peptide stability and product manufacture present in previously examined formulation approaches. In the second, we will develop an implantable polymer device for drug delivery to the eye to treat optic neuropathy. Such devices have recently been approved for use in humans; however, drug release and device degradation are not controllable and if complications arise, removal of the implanted device is problematic. Our approach to solving these issues will be to utilize photo-cleavable linkages to form a polymer capable of photo-activated degradation. As the eye is optically accessible, this approach will provide a means of rapidly eliminating the implant once drug release is complete or should removal be required due to complications. In the tendon tissue engineering focus of the program, we will design and assess new copolymers to be used in an additive manufacturing technique referred to as melt electrowriting to prepare scaffolds with defined architectures that mimic the mechanical behavior of the Achilles tendon. These new copolymers will be thermally stable to allow for effective melt processing yet photo-cross-linkable. Our photo-crosslinking design will provide creep resistance and increased stiffness to the scaffold while maintaining cell compatibility. The trainees supported by this research program will gain the necessary skills and develop innovations to contribute to the emerging biomedical engineering industry in Canada.