Self Sustaining Scaffolds

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As biomaterials science evolved very simple classifications such as bioinert, bioactive or bioresorbable were developed to categorise them related to solubility. Many fascinating materials-tissue interactions originally classified as `bioactive' were never explained, in particular tissue inductive materials. Materials that induced bone to form in soft tissues were initially observed as artifacts and while reproducible were not understood. We proposed that the cause of osteoinduction by simple ceramic formulations must be ionic in origin and this gave rise to many papers illustrating how calcium and phosphate ion control could alter bone repair.  The applicant recently discovered that large diameter blood vessels could be induced to sprout and form new vascular trees that can oxygenate entirely new volumes. These vessels are 1 mm in diameter and so can be cut off and reattached to an artery elsewhere in the body, thereby overcoming a huge impediment to tissue reconstruction. The broadening of the scope of inductive materials beyond bone is important as it indicates a more general effect and a new way to develop repair technologies. Based on prior discovery grant supported research, the applicant conceived materials that could take over some of the functions of the vasculature, locally oxygenating and detoxifying ischemic tissues. The problem is deceptively simple: supply oxygen, nutrients and remove waste. However, doing this at the right time in the right amount requires development of multiple material constructs in forms that are compatible with existing work flow. This is challenging; requiring an identification and understanding of the parameter to be modified without altering the other release or adsorption profiles of the materials and keeping with the narrow boundaries delineated by the requirement of non-toxicity or complete resorption. The applicant has succeeded in preventing necrosis in poorly vascularized wounds in a pilot proof of concept study. He has in the past year extended this to injectable forms that can prevent secondary necrosis in skin. Muscle is extremely challenging to preserve or regenerate without a blood supply. While cells capable of muscle regeneration can be produced, no technology exists to sustain them inside after implantation long enough for regeneration to occur. Using our approach we can sustain cell viability at 1-2 x 108 cells/ml. In this application, we will develop bioinks based on our approach to sustain and temporarily immuno-isolate myoblasts as living tissue constructs that can survive without vasculature long enough to survive the initial inflammation and revascualrisation phase following implantation. Being able to create cell constructs in large 3D volumes eliminates one of the obstacles to engineering full tissue analogues. The proposal is concerned with determining mechanisms and limits to biomaterials-based control of tissue sustaining microenvironments in order to achieve this.