Laminin-111-Enriched Fibrin Hydrogels Enhance Functional Muscle Regeneration Following Trauma.

Volumetric muscle loss (VML) is the surgical or traumatic loss of skeletal muscle, which can cause loss of limb function or permanent disability. VML injuries overwhelms the endogenous regenerative capacity of skeletal muscle and results in poor functional healing outcomes. Currently, there are no approved tissue engineering treatments for VML injuries. In this study, fibrin hydrogels enriched with laminin-111 (LM-111; 50-450 µg/mL) were used for the treatment of VML of the tibialis anterior in a rat model. Treatment with fibrin hydrogel containing 450 µg/mL of LM-111 (FBN450) improved muscle regeneration following VML injury. FBN450 hydrogel treatment increased the relative proportion of contractile to fibrotic tissue as indicated by the myosin: collagen ratio on day 28 post-VML injury. FBN450 hydrogels also enhanced myogenic protein expression and increased the quantity of small to medium size myofibers (500-2000 µm2) as well as innervated myofibers. Improved contractile tissue deposition due to FBN450 hydrogel treatment resulted in a significant improvement (∼60%) in torque production at day 28 postinjury. Taken together, these results suggest that the acellular FBN450 hydrogels provide a promising therapeutic strategy for VML that is worthy of further investigation. Impact statement Muscle trauma accounts for 50-70% of total military injuries and complications involving muscle result in ∼80% of delayed amputations. The lack of a clinical standard of care for volumetric muscle loss (VML) injuries presents an opportunity to develop novel regenerative therapies and improve healing outcomes. Laminin-111-enriched fibrin hydrogel may provide a promising therapy for VML that is worthy of further investigation. The acellular nature of these hydrogels will allow for easy off the shelf access to critically injured patients and fewer regulatory hurdles during commercialization.

The Role of Innate and Adaptive Immune Cells in Skeletal Muscle Regeneration.

Skeletal muscle regeneration is highly dependent on the inflammatory response. A wide variety of innate and adaptive immune cells orchestrate the complex process of muscle repair. This review provides information about the various types of immune cells and biomolecules that have been shown to mediate muscle regeneration following injury and degenerative diseases. Recently developed cell and drug-based immunomodulatory strategies are highlighted. An improved understanding of the immune response to injured and diseased skeletal muscle will be essential for the development of therapeutic strategies.

Preliminary investigation of honey-doped electrospun scaffolds to delay wound closure.

Manuka honey is an ancient remedy to improve wound healing; however, an effective delivery system is needed to facilitate extended release of honey into wounds. We developed an electrospun dermal regeneration template consisting of a poly (ε-caprolactone) (PCL) scaffold embedded with 1%, 5%, 10%, or 20% manuka honey. In vitro studies demonstrated that honey PCL scaffolds were not toxic to macrophages, and they allowed for macrophage infiltration into the scaffolds. Vascular endothelial growth factor (VEGF), a marker of angiogenesis, was released by macrophages cultured with scaffolds and macrophage/scaffold conditioned media promoted endothelial cell tube formation in an angiogenesis assay. In a full thickness murine wound model, the scaffolds prevented rapid wound contraction. In vivo, cells infiltrated the scaffolds by post-wounding day 7, but the honey scaffolds did not affect collagen deposition at that time. In summary, preliminary studies investigating the effect of honey on tissue repair show that scaffolds prevent rapid wound contraction, allow for cell infiltration, and promote angiogenesis. © 2019 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 107B:2620-2628, 2019.