Development and application of an in-situ forming, biohybrid scaffold for wound repair

• Main Author: Hartwell, Ryan Victor
• Language: English
• Published: University of British Columbia 2015
• Online Access: http://hdl.handle.net/2429/52516

Tissue engineering has advanced rapidly over the past decade in an effort to address unmet medical needs in burn and chronic wound treatment. Each year, over 1 million patients seek medical attention for burn injuries in North America. Moreover, chronic wounds in the elderly and those with diabetes comprise the largest single segment of wound care. Without question current treatments are costly and challenging for healthcare professionals. When autografts are not possible, skin substitutes are often employed as alternative coverage. Although these strategies have dramatically improved healing in patients, they are limited by the time they take to fully integrate with surrounding tissue. Our idea to bridge the gap is to create a patient-ready skin substitute. Moving toward a skin substitute that is readily available for the patient, I developed an in-situ gelling scaffold that permits integration with surrounding tissue. Furthermore, it was my goal to create a system that resists cell mediated contracture and digestion, and provide an ideal environment for tissue repair. My hypothesis was that the fabrication of a composite matrix of collagen and a blended-polymer hydrogel would result in a material that could be lyophilized, reconstituted and gel rapidly in-situ. The objectives of this work are fourfold: (1) develop, characterize, optimize and evaluate the functionality of a reconstitutable in situ forming scaffold in vitro; (2) evaluate the efficacy of the scaffold to perform within an acute wound; (3) evaluate methods to tailor the scaffold to be used as a cell delivery vehicle; and (4) develop a prototype model product that could translated to the clinic. Satisfying the objectives of this work have demonstrated that with a biocompatible concentration of hydrogel collagen fibrillogenesis activation energy can be lowered, and the mechanical and physical properties of the resulting scaffold are enhanced. The resulting scaffold can be further lyophilized and reconstituted to form composite skin and other matrices both in vitro and in vivo. Assuming that regulatory requirements are met, the scaffold has the potential to improve the quality of life of patients with devastating chronic wounds and burns, and advance further knowledge in the field of tissue engineering. === Medicine, Faculty of === Medicine, Department of === Experimental Medicine, Division of === Graduate