A Novel Biomimetic Scaffold Design that Accelerates Long Bone Segment Defect Regeneration
Abstract
Background: Critical size long bone defects, which will not heal without surgical intervention, can result from combat wounds in military personnel. According to the Army Physical Evaluation Board, severe musculoskeletal trauma is the most common disabling condition experienced by Service personnel, with 54% of those injuries involving extremities. In the civilian population, these defects also result from severe traumatic injuries or large bone resections secondary to cancer treatment. Although surgical options exist to address this problem, all current methods have drawbacks that include long periods of non-weight bearing and poor long-term success rates. Failure of surgical treatments can lead to amputation resulting in significant morbidity, inability to return to previous activities, and significant physical and psychological impairment. This is a critical problem resulting in an enormous financial burden to the military. A need exists for a treatment that can bridge critical size long bone defects that is rapid, reliable, and eliminates the extensive period of non-weight bearing required with all the current surgical treatments. Objective: The overall goal of this research program is to utilize novel implantable sensate scaffolds that allow immediate limb loading, facilitate rapid regeneration of bone across a critical size defect, and allow accurate real-time monitoring of tissue and scaffold loads that can be used to guide patient-specific rehabilitation protocols. This project will test a promising biomimetic scaffold that can be produced in a patient-specific fashion using x-ray computed tomography (CT) scans coupled to a freeform fabrication three-dimensional printing technique. These scaffolds have previously facilitated rapid bone formation and ingrowth, particularly when seeded with adult adipose-derived mesenchymal stem cells (MSCs). In addition, the scaffolds incorporate sensors that can be used to define loading of the scaffold and surrounding tissues. Measurements obtained from these sensors are critical to translating the technology from an animal model to patients by allowing the development and testing of rehabilitation protocols designed to accelerate bone healing and remodeling. Ultimately, the use of a sensate implant will allow real-time measurements that can be used to determine the effect of pharmaceutical treatments, guide patient-specific rehabilitation, and facilitate clinical decision-making by allowing evaluation of functional bone formation and provide a technique to detect and address any pending catastrophic event prior to implant failure. A hypothesis of this overall goal is that the appropriate scaffold, stem cells, and loading environment are necessary to rapidly generate bone in order to bridge a very large defect in a load-bearing long bone. Specific Aims: This proposal includes three specific aims intended to develop the technology to a point where a clinical trial will be possible. The first aim uses implantable biomimetic “sensate” scaffolds to test whether increased loading across a critical size defect during the healing process accelerates bone formation. The second aim tests the quality of the bone that is formed by removing supporting internal hardware to demonstrate that the bone formed can withstand long-term normal physiologic loading. The third aim develops and tests bioceramic patient-specific scaffolds that will ultimately be used in clinical trials and simultaneously compares the current scaffold material to the next-generation materials that can provide increased strength and durability for patients with highly demanding activity levels. Relevance: Development of rapidly deployable, adult stem cell infiltrated biomimetic sensate scaffolds will provide a method of regenerating damaged or missing load-bearing long bone segments in Service personnel. These segments will be sturdy enough to allow immediate limb loading and rehabilitation with the
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Oct 29, 2018
- Source ID
- W81XWH1810490
Entities
People
- John Szivek
Organizations
- United States Army
- University of Arizona