Decorin-supplemented collagen hydrogels for the co-delivery of bone morphogenetic protein-2 and microvascular fragments to a composite bone-muscle injury model with impaired vascularization.

Traumatic musculoskeletal injuries that result in bone defects or fractures often affect both bone and the surrounding soft tissue. Clinically, these types of multi-tissue injuries have increased rates of complications and long-term disability. Vascular integrity is a key clinical indicator of injury severity, and revascularization of the injury site is a critical early step of the bone healing process.

Enhanced in vivo retention of low dose BMP-2 via heparin microparticle delivery does not accelerate bone healing in a critically sized femoral defect.

Unlabelled: Bone morphogenetic protein-2 (BMP-2) is an osteoinductive growth factor used clinically to induce bone regeneration and fusion. Some complications associated with BMP-2 treatment have been attributed to rapid release of BMP-2 from conventional collagen scaffolds, motivating the development of tunable sustained-release strategies. We incorporated BMP-2-binding heparin microparticles (HMPs) into a hydrogel scaffold to improve spatiotemporal control of BMP-2 delivery to large bone defects.

Guidelines for Models of Skeletal Muscle Injury and Therapeutic Assessment.

Volumetric muscle loss (VML) injuries present a large clinical challenge with a significant need for new interventions. While there have been numerous reviews on muscle injury models, few have critically evaluated VML models. The objective of this review is to discuss current preclinical models of VML in terms of models, analytical outcomes, and therapeutic interventions, and to provide guidelines for the future use of preclinical VML models.

Functional augmentation of naturally-derived materials for tissue regeneration.

Tissue engineering strategies have utilized a wide spectrum of synthetic and naturally-derived scaffold materials. Synthetic scaffolds are better defined and offer the ability to precisely and reproducibly control their properties, while naturally-derived scaffolds typically have inherent biological and structural properties that may facilitate tissue growth and remodeling. More recently, efforts to design optimized biomaterial scaffolds have blurred the line between these two approaches.

Functional analysis of limb recovery following autograft treatment of volumetric muscle loss in the quadriceps femoris.

Severe injuries to the extremities often result in muscle trauma and, in some cases, significant volumetric muscle loss (VML). These injuries continue to be challenging to treat, with few available clinical options, a high rate of complications, and often persistent loss of limb function. To facilitate the testing of regenerative strategies for skeletal muscle, we developed a novel quadriceps VML model in the rat, specifically addressing functional recovery of the limb.

Recovery from hind limb ischemia enhances rhBMP-2-mediated segmental bone defect repair in a rat composite injury model.

Although severe extremity trauma is often inclusive of skeletal and vascular damage in combination, segmental bone defect repair with concomitant vascular injury has yet to be experimentally investigated. To this end, we developed a novel rat composite limb injury model by combining a critically-sized segmental bone defect with surgically-induced hind limb ischemia (HLI). Unilateral 8mm femoral defects were created alone (BD) or in combination with HLI (BD + HLI), and all defects were treated with rhBMP-2 via a hybrid biomaterial delivery system.

Attenuated human bone morphogenetic protein-2-mediated bone regeneration in a rat model of composite bone and muscle injury.

Extremity injuries involving large bone defects with concomitant severe muscle damage are a significant clinical challenge often requiring multiple treatment procedures and possible amputation. Even if limb salvage is achieved, patients are typically left with severe short- and long-term disabilities. Current preclinical animal models do not adequately mimic the severity, complexity, and loss of limb function characteristic of these composite injuries.