We have recently discovered that skeletally immature and adolescent animals have a functionally successful repair response to ACL injury when a tissue engineering repair strategy is used. This strategy utilizes a collagen scaffold with an optimized platelet solution (a collagen-platelet composite, CPC) to enhance healing in the ligament wound site. We discovered that the strength of the ACL after three months of healing using a CPC was equivalent to the strength of an ACL reconstruction graft, the current gold standard of treatment. Further study demonstrated that the post-traumatic osteoarthritis seen in patients and animals alike after ACL reconstruction was not seen in animals undergoing CPC-enhanced repair of the ACL.
The aims of this current revision (formerly known as a competing supplement) are to expand the focus of the current parent R01 in order to prepare this new technology for the first-in-human use. The two major requirements this work would fulfill would be 1) to verify and validate a terminal sterilization technique for the collagen scaffold. Our current process involves making the collagen scaffold using a """"""""sterile process"""""""" - everything that touches the component materials of the scaffold needs to be sterile, which is expensive and time-consuming. In contrast, terminal sterilization allows for non-sterile processing of the biomaterial and then sterilization of the final product. This results in a 10-fold reduction in manufacturing costs, and the FDA requires a terminal sterilization step, or evidence that one is not possible without harming the device efficacy. The second phase of work would involve biocompatibility studies of the collagen scaffold. This would include testing for cytotoxicity, sensitization, systemic toxicity and implantation testing. The completion of these two phases of study would allow us to use this finalized scaffold in the work to be performed in Aim 2 of the parent R01, thus simultaneously generating the data required by the FDA on the final product and completing the scientific aims of the parent grant with one experiment, rather than having to run a second trial for the FDA clearance. This would save significant expenditures required to translate this technology to human patients. We have already tried to get funding for this requisite supplemental work from industry and private sector investing;however, we have been told this type of novel technology would be too disruptive to current streams of revenue for major orthopedic companies in the area of ACL treatment, and thus, their level of interest in supporting these studies is low. Therefore, this grant mechanism currently represents our sole avenue through to clinical studies and first-in-human use of this novel technique which could result in a paradigm shift in ligament and tendon repair technology. With the time line of the parent grant, this is our only chance to apply for this supplemental funding.
ACL injuries affect over a half million people in the US each year. We have developed a novel technique of treatment ACL injuries using a bio-engineered scaffold to stimulate the ligament to heal and regenerate after injury. This new technique also prevents the post-traumatic osteoarthritis seen after the current gold standard of ACL treatment, ACL reconstruction. This grant would provide funding for the last two critical steps required before going to human trial of this less-invasive technique of ACL repair and regeneration.
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