Triple growth factor delivery promotes functional bone regeneration following composite musculoskeletal trauma.

Successful bone healing in severe trauma depends on early revascularization to restore oxygen, nutrient, growth factor, and progenitor cell supply to the injury. Therapeutic angiogenesis strategies have therefore been investigated to promote revascularization following severe bone injuries; however, results have been inconsistent. This is the first study investigating the effects of dual angiogenic growth factors (VEGF and PDGF) with low-dose bone morphogenetic protein-2 (BMP-2; 2.

Early systemic immune biomarkers predict bone regeneration after trauma.

Severe traumatic injuries are a widespread and challenging clinical problem, and yet the factors that drive successful healing and restoration of function are still not well understood. One recently identified risk factor for poor healing outcomes is a dysregulated immune response following injury. In a preclinical model of orthopedic trauma, we demonstrate that distinct systemic immune profiles are correlated with impaired bone regeneration.

Effects of controlled dual growth factor delivery on bone regeneration following composite bone-muscle injury.

The objective of this study was to investigate the controlled release of two growth factors (BMP-2 and VEGF) as a treatment strategy for bone healing in clinically challenging composite injuries, consisting of a femoral segmental bone defect and volumetric muscle loss. This is the first investigation of dual growth factor delivery in a composite injury model using an injectable delivery system consisting of heparin microparticles and alginate gel. The loading efficiency of growth factors into these biomaterials was found to be >90%, revealing a strong affinity of VEGF and BMP-2 to heparin and alginate.

Wireless sensor enables longitudinal monitoring of regenerative niche mechanics during rehabilitation that enhance bone repair.

Mechanical loads exerted on the skeleton during activities such as walking are important regulators of bone repair, but dynamic biomechanical signals are difficult to measure inside the body. The inability to measure the mechanical environment in injured tissues is a significant barrier to developing integrative regenerative and rehabilitative strategies that can accelerate recovery from fracture, segmental bone loss, and spinal fusion. Here we engineered an implantable strain sensor platform and longitudinally measured strain across a bone defect in real-time throughout rehabilitation.

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.

Effects of BMP-2 dose and delivery of microvascular fragments on healing of bone defects with concomitant volumetric muscle loss.

Traumatic composite bone-muscle injuries, such as open fractures, often require multiple surgical interventions and still typically result in long-term disability. Clinically, a critical indicator of composite injury severity is vascular integrity; vascular damage alone is sufficient to assign an open fracture to the most severe category. Challenging bone injuries are often treated with bone morphogenetic protein 2 (BMP-2), an osteoinductive growth factor, delivered on collagen sponge.

Determination of a Critical Size Threshold for Volumetric Muscle Loss in the Mouse Quadriceps.

The goal of this study was to determine the threshold for a critically sized, nonhealing muscle defect by characterizing key components in the balance between fibrosis and regeneration as a function of injury size in the mouse quadriceps. There is currently limited understanding of what leads to a critically sized muscle defect and which muscle regenerative components are functionally impaired. With the substantial increase in preclinical VML models as testbeds for tissue engineering therapeutics, defining the critical threshold for VML injuries will be instrumental in characterizing therapeutic efficacy and potential for subsequent translation.

Aggregate mesenchymal stem cell delivery ameliorates the regenerative niche for muscle repair.

Duchenne muscular dystrophy is a severe muscle wasting disease due to the absence of the dystrophin protein from the muscle cell membrane, which renders the muscle susceptible to continuous damage. In Duchenne muscular dystrophy patients, muscle weakness, together with cycles of degeneration/regeneration and replacement with noncontractile tissue, limit mobility and lifespan. Because the loss of dystrophin results in loss of polarity and a reduction in the number of self-renewing satellite cells, it is postulated that these patients could achieve an improved quality of life if delivered cells could restore satellite cell function.

Decorin-containing collagen hydrogels as dimensionally stable scaffolds to study the effects of compressive mechanical loading on angiogenesis.

Angiogenesis is a critical component during wound healing, and the process is sensitive to mechanical stimuli. Current culture environments used to investigate three-dimensional microvascular growth often lack dimensional stability and the ability to withstand compression. We investigated the ability of decorin, a proteoglycan known to modulate collagen fibrillogenesis, incorporated into a collagen hydrogel to increase construct dimensional stability while maintaining vascular growth.

Skeletal Myoblast-Seeded Vascularized Tissue Scaffolds in the Treatment of a Large Volumetric Muscle Defect in the Rat Biceps Femoris Muscle.

High velocity impact injuries can often result in loss of large skeletal muscle mass, creating defects devoid of matrix, cells, and vasculature. Functional regeneration within these regions of large volumetric muscle loss (VML) continues to be a significant clinical challenge. Large cell-seeded, space-filling tissue-engineered constructs that may augment regeneration require adequate vascularization to maintain cell viability.

β sheets not required: combined experimental and computational studies of self-assembly and gelation of the ester-containing analogue of an Fmoc-dipeptide hydrogelator.

In our work toward developing ester-containing self-assembling peptides as soft biomaterials, we have found that a fluorenylmethoxycarbonyl (Fmoc)-conjugated alanine-lactic acid (Ala-Lac) sequence self-assembles into nanostructures that gel in water. This process occurs despite Fmoc-Ala-Lac's inability to interact with other Fmoc-Ala-Lac molecules via β-sheet-like amide-amide hydrogen bonding, a condition previously thought to be crucial to the self-assembly of Fmoc-conjugated peptides. Experimental comparisons of Fmoc-Ala-Lac to its self-assembling peptide sequence analogue Fmoc-Ala-Ala using a variety of microscopic, spectroscopic, and bulk characterization techniques demonstrate distinct features of the two systems and show that while angstrom-scale self-assembled structures are similar, their nanometer-scale size and morphological properties diverge and give rise to different bulk mechanical properties.