R43AR079966

Evaluation of Extracellular Matrix Gel for Adhesion Prevention and Tissue Healing in Tendon Surgery - Project Summary

Approximately 32M musculoskeletal injuries in the US cost nearly $322B annually (1). The high economic burden is due in part to post-operative scar formation (i.e., adhesions), which is the leading cause of disability following tendon surgery (4, 5).

We are developing a sprayable adhesion barrier derived from extracellular matrix (ECM spray), which serves as a mechanical barrier and elicits a healing response from the patient’s own body to prevent adhesions from forming.

Around 1.5M patients suffer flexor tendon injuries each year, and as many as 30-40% of these individuals will subsequently have limited range of motion due to adhesions (6). Current options to mitigate adhesions are limited and flawed, and there is an unmet need for a technology which can safely and effectively prevent adhesion formation to maintain normal joint function after tendon injury.

ECM spray is thermally responsive, forming a thin film hydrogel over the tissue where applied and prevents adhesions by acting as a mechanical barrier between adjacent tissues. Application of ECM spray as the last step of a surgical procedure resulted in >70% reduction in post-operative adhesions in abdominal and pelvic animal models of adhesion formation.

A major limitation of currently available orthopedic tendon protectors/adhesion barriers is that they are bulky sheets unable to conform to the region of the repaired flexor tendon and therefore impair tendon movement/gliding. Newer thin sheet products are available, but surgeons describe them as performing like "wet toilet paper" because they disintegrate upon hydration.

ECM spray is applied as a liquid, rather than a sheet, to conform to the repaired flexor tendon and surrounding flexor tendon sheath. Past attempts at developing sprayable adhesion barriers have been unsuccessful, in part because of impaired tissue healing after application. While it remains unknown what impact ECM spray will have upon tendon healing, we have shown that ECM spray acts as an inductive scaffold to support constitutive repair of the peritoneum.

Based upon these data, the objective of the present study is to determine ECM spray's safety, efficacy, and usability in orthopedic surgery following flexor tendon injury. In Aim 1, we will characterize tenocyte cellular response to ECM spray, which will determine if ECM is biocompatible and supportive of tenocyte and synoviocyte growth. In Aim 2, we will determine if ECM spray is effective for reducing tendon adhesion formation without compromising the biomechanics of healing tendons. In Aim 3, we will demonstrate usability in human anatomy, which is critical to surgeon adoption and commercialization.

Results from this safe-by-design approach will lead to key research and development milestones necessary for use of ECM spray in orthopedic surgery and could ultimately improve the lives of the millions affected each year by adhesion-related morbidity.

Tybr Health

THE NATIONAL INSTITUTE OF AND MUSCULOSKELETAL AND SKIN DISEASES (NIAMS) MISSION IS TO SUPPORT RESEARCH INTO THE CAUSES, TREATMENT, AND PREVENTION OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES, TRAINING OF BASIC AND CLINICAL SCIENTISTS TO CARRY OUT THIS RESEARCH, AND DISSEMINATION OF INFORMATION ON RESEARCH PROGRESS IN THESE DISEASES. THE EXTRAMURAL PROGRAM PROMOTES AND SUPPORTS BASIC, TRANSLATIONAL, AND CLINICAL STUDIES OF SYSTEMIC RHEUMATIC AND AUTOIMMUNE DISEASES, SKIN BIOLOGY AND DISEASES, BONE BIOLOGY AND DISEASES, MUSCLE BIOLOGY AND DISEASES, AND JOINT BIOLOGY AND DISEASES AND ORTHOPAEDICS. NIAMS SYSTEMIC RHEUMATIC AND AUTOIMMUNE DISEASES PROGRAMS ADDRESS BASIC, TRANSLATIONAL, AND CLINICAL RESEARCH, INCLUDING CLINICAL TRIALS AND OBSERVATIONAL AND MECHANISTIC STUDIES, FOCUSED ON IMMUNE-MEDIATED ARTHRITIS AND AUTOIMMUNE-RELATED ACUTE AND CHRONIC DISORDERS IN ADULTS AND CHILDREN. NIAMS SKIN BIOLOGY AND DISEASES PROGRAMS SUPPORT BASIC, TRANSLATIONAL, AND CLINICAL RESEARCH IN SKIN, INCLUDING BOTH COMMON AND RARE SKIN DISEASES. THESE PROGRAMS INCLUDE INVESTIGATIONS OF THE BASIC MOLECULAR, CELLULAR, AND DEVELOPMENTAL BIOLOGY OF SKIN, AS WELL AS STUDIES OF SKIN AS AN IMMUNE, SENSORY, ENDOCRINE, AND METABOLIC ORGAN. NIAMS BONE BIOLOGY AND DISEASES PROGRAMS SUPPORT RESEARCH ON THE CONTROL OF BONE FORMATION, RESORPTION, AND MINERALIZATION AS WELL AS THE EFFECTS OF SIGNALING MOLECULES ON BONE CELLS. THEY SUPPORT CLINICAL STUDIES OF INTERVENTIONS TO PREVENT FRACTURES ASSOCIATED WITH OSTEOPOROSIS AND RESEARCH INTO LESS COMMON BONE DISEASES. NIAMS MUSCLE BIOLOGY AND DISEASES PROGRAMS ENCOURAGE RESEARCH ON MUSCLE DEVELOPMENTAL BIOLOGY, GROWTH, MAINTENANCE, AND HYPERTROPHY, PHYSIOLOGY OF CONTRACTION, STRUCTURAL BIOLOGY OF THE CONTRACTILE APPARATUS, DISEASE MECHANISMS, BIOMARKERS AND OUTCOME MEASURES, AND DEVELOPMENT AND CLINICAL TESTING OF THERAPIES FOR CONDITIONS INCLUDING THE MUSCULAR DYSTROPHIES. NIAMS JOINT BIOLOGY, DISEASES, AND ORTHOPAEDICS PROGRAMS SUPPORT A BROAD SPECTRUM OF RESEARCH CENTERED ON THE INTERPLAY AMONG THE BODY'S MUSCLES, BONES, AND CONNECTIVE TISSUES. THEY ENCOURAGE TISSUE ENGINEERING AND REGENERATIVE MEDICINE RESEARCH, MOLECULAR BIOLOGY, IMAGING, AND CLINICAL RESEARCH, AND THE TREATMENT AND PREVENTION OF ORTHOPAEDIC CONDITIONS. NIAMS PARTICIPATES IN THE SMALL BUSINESS INNOVATION RESEARCH (SBIR) AND SMALL BUSINESS TECHNOLOGY TRANSFER (STTR) PROGRAMS. THE SBIR PROGRAM IS INTENDED TO INCREASE PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT, TO INCREASE SMALL BUSINESS PARTICIPATION IN FEDERAL RESEARCH AND DEVELOPMENT, AND TO FOSTER AND ENCOURAGE PARTICIPATION OF SOCIALLY AND ECONOMICALLY DISADVANTAGED SMALL BUSINESS CONCERNS AND WOMEN-OWNED SMALL BUSINESS CONCERNS IN TECHNOLOGICAL INNOVATION. THE STTR PROGRAM IS INTENDED TO STIMULATE AND FOSTER SCIENTIFIC AND TECHNOLOGICAL INNOVATION THROUGH COOPERATIVE RESEARCH AND DEVELOPMENT CARRIED OUT BETWEEN SMALL BUSINESS CONCERNS AND RESEARCH INSTITUTIONS, TO FOSTER TECHNOLOGY TRANSFER BETWEEN SMALL BUSINESS CONCERNS AND RESEARCH INSTITUTIONS, TO INCREASE PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT, AND TO FOSTER AND ENCOURAGE PARTICIPATION OF SOCIALLY AND ECONOMICALLY DISADVANTAGED SMALL BUSINESS CONCERNS AND WOMEN-OWNED SMALL BUSINESS CONCERNS IN TECHNOLOGICAL INNOVATION.

93.846 - Arthritis, Musculoskeletal and Skin Diseases Research

National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) [HHS - NIH]

Houston, Texas 770212041 United States

Single Zip Code

PHS 2021-2 Omnibus Solicitation of the NIH, CDC and FDA for Small Business Innovation Research Grant Applications (Parent SBIR [R43/R44] Clinical Trial Not Allowed) (PA-21-259)

Amendment Since initial award the End Date has been extended from 08/31/23 to 08/31/24.