We propose to create collagen-based constructs using slices of decellularized tendon and study their mechanical and biological properties both in vitro and in vivo. Tendon is comprised of many highly organized type-I collagen fibers that make up 85% of the dry weight. The collagen found in tendon is highly aligned in a linear manner whereas collagen in other tissue such as skin may be more randomly oriented. This organization provides strength to the material while also providing micro and nanoscale guidance contact which have been shown to influence cell growth. We hypothesize that decellularized tendon can provide collagen for the construction of scaffolds that maintain the strength and structure of native collagen. It is possible to generate a new family of tissue-derived, nanostructured materials with superior mechanical properties for biomedical applications from the decellularized tendon using a combination of sectioning, stacking and rolling. To achieve this goal, we propose the following specific aims:
Specific Aim 1. Optimize the fabrication process and study the mechanical properties of the tendon- derived constructs. In this aim, we will optimize the fabrication process using a combination of slicing and stacking (and rolling) from decellularized bovine tendons. We will tune the mechanical properties by controlling fiber alignment, section thickness, and types of crosslinking. The composite materials, e.g. tendon constructs coated with collagen gel or elastin gel, will also be prepared and studied.
Specific Aim 2. Study the biological function of the tendon-derived constructs. In this aim, we will determine the thrombogenic potential and the immunological response of the prosthetic grafts using in vitro cell culture. These tendon-derived constructs will further be studied in vivo for their biocompatibility by subcutaneous implantation in rats. These results will provide useful instruction for next step biomedical applications, including artificial blood vessel, nerve conduits or patches for rotator cuff repair.
We aim to fabricate 2D stacked and 3D tubular constructs from sections of tendon, a soft connective tissue comprising precisely packed, well-aligned bundles of collagen nanofibers;and study the mechanical and biological properties of these constructs both in vitro and in vivo.
|Alberti, Kyle A; Hopkins, Amy M; Tang-Schomer, Min D et al. (2014) The behavior of neuronal cells on tendon-derived collagen sheets as potential substrates for nerve regeneration. Biomaterials 35:3551-7|