Improving Wound Healing and Recovery by Blocking Excessive Scar Formation in Peripheral Nerves, Muscles, and Joints After Composite Injuries to Extremities
Abstract
Objectives and Rationale: While scarring from injuries is normal and helps the body rebuild, excessive scarring can cause significant physical and psychological burdens and delayed return to military duties after traumatic limb injuries. Soldiers are uniquely prone to suffer from complex limb injuries due to the risks associated with their military activities. About half of all combat injuries to the musculoskeletal system involve the limbs. One of the significant complications of these injuries is post-traumatic scarring, which severely limits the regeneration of damaged limb tissues, including ligaments, tendons, joint capsules, muscles, and nerves. Thus, the overarching long-term goal of this study is to help wounded Soldiers recover from injuries to their limbs by applying a therapeutic antibody (referred to as ACA) that prevents excessive scarring of injured tissues. Although surgery and lengthy physical therapies can reduce unwanted scarring, these interventions have poor outcomes and are not fully effective. Furthermore, no currently available medications have been proven to reduce excessive scar buildup effectively and safely. However, we are exploring using the antibody-based system to reduce scarring through antibody-based therapeutics, the fastest-growing class of modern drugs due to their high effectiveness, specificity, and safety. Responding to the need to regain limb function, we developed ACA to block the formation of excessive fibrotic scars responsible for poor functional recovery. We have already demonstrated the effectiveness and safety of this antibody in a relevant animal model of limb injury. Here, we will move our antibody-based therapeutic closer to human trials by providing bases for its use in regenerating composite tissue injuries to the joints, muscles, and peripheral nerves. Alignment with FY22 PRORP Strategic Goals: This proposal is in response to the Peer Reviewed Orthopaedic Research Program: Applied Research Award (Funding Opportunity Number: W81XWH-22-PRORP-ARA). The proposed study aligns with the Focus Area Composite Tissue Regeneration. By targeting excessive scarring, a central barrier to the regeneration of musculoskeletal and neural tissues, with an advanced humanized therapeutic antibody, our proposal aligns with this Focus Area precisely. Benefit for Service Members: The leading patient group that will benefit from this study is Service Members who have sustained trauma to their extremities. Since post-traumatic scarring is a leading cause of poor limb function recovery, applying our anti-scarring antibody is the right approach to reducing the excessive scarring problem. Thus, our research study will have an immediate positive impact on the healing of the limbs. It will also positively affect functional recovery and return to military service in the long term. Consequently, faster, more predictable recovery will allow injured Soldiers to resume their military activities and help to maintain unit readiness. Moreover, returning to military or civil work activities will positively impact the well-being of Soldiers Families and help reduce the burden imposed on caregivers. Since the consequences of excessive post-traumatic scarring overlap in military and civilian populations, the proposed therapy will have a broad positive impact on many patients. Far-Reaching Clinical Applications: Although our main target here is to reduce excessive post-traumatic scarring in extremities, the potential clinical applications of our technology in military personnel are far-reaching. They include reducing burn scars, limiting abdominal adhesions, blocking ocular scarring, and others. Since clinically used therapeutic antibodies are generally safe, we expect no significant risks associated with our approach. Furthermore, our research will positively impact broad research activities to heal wounded tissues better. By demonstrating ACA s effectiveness in reducing ex
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Jan 04, 2024
- Source ID
- HT94252310638
Entities
People
- Andrzej Fertala
Organizations
- Thomas Jefferson University
- United States Army