Grant: Discovery Launch Supplement

The human body is very complex and adept at healing itself, but in some instances requires intervention to fully address chronic diseases and injury. New biomaterial systems that are patient-personalized, multi-functional and modelled after molecules involved in key healing processes in the human body are of high novelty and interest. Building upon the applicant's research experience the proposed program will develop new externally stimulated and polymeric local delivery systems (LDS) capable of targeting diseases and injuries of significant clinical concern. In the short-term dressings for healing chronic wounds, such as diabetic foot ulcers (DFU), will be developed. In Canada alone there is currently more than 4 million individuals living with diabetes and of these 19 - 34 % are expected to develop a DFU in their lifetime. Unfortunately, traditional wound dressings consisting of cotton bandage and/or gauze both decrease the healing rate and increase pain when dressing is removed. Meanwhile, current alternative dressings have not achieved significant clinical translation owing in part to poor mechanical and/or swelling properties. As a result, therapy for DFU remains a notable clinical challenge and would greatly benefit from a new biomaterial system and approach. 3D printing (3DP) is one cost-effective method for fabricating wound dressings, yet the materials so far explored for 3DP have achieved limited success in wound treatment. Polyphosphates, while new to 3DP, are involved in numerous functions in the human body including healing and can offer notable antibacterial and coagulative properties; they show significant potential towards the proposed biomaterial system. The short-term objectives for the proposed research program involve 3DP of polyphosphate: (1) using physical crosslinking with simple salts, (2) using chemical crosslinking following polyphosphate functionalization, and (3) loaded with externally stimulated therapeutic agents. All investigations towards these objectives will utilize structure-property-function feedback paradigm to help in any design decisions and data analysis. The experimental results and analysis obtained during this program will advance the knowledge and design of biomaterials for 3DP, as well as for LDS towards external-stimulated therapy. The pharmaceutical and biomedical industries will also benefit from improved understanding of any interactions between carrier material and therapeutic agent to optimize design and clinical translation of LDS'. Furthermore, with more functionally driven and personalized design of the LDS', improvements in healing outcomes are also expected, thus contributing to the reduced build-up of antibiotic-resistant superbugs, reduced treatment costs, and improved patient outcomes.