In vivo printing of growth factor-eluting adhesive scaffolds improves wound healing

Acute and chronic wounds affect millions of people around the world, imposing a growing financial burden on patients and hospitals. Despite the application of current wound management strategies, the physiological healing process is disrupted in many cases, resulting in impaired wound healing. Therefore, more efficient and easy-to-use treatment modalities are needed. In this study, we demonstrate the benefit of in vivo printed, growth factor-eluting adhesive scaffolds for the treatment of full-thickness wounds in a porcine model. A custom-made handheld printer is implemented to finely print gelatin-methacryloyl (GelMA) hydrogel containing vascular endothelial growth factor (VEGF) into the wounds. In vitro and in vivo results show that the in situ GelMA crosslinking induces a strong scaffold adhesion and enables printing on curved surfaces of wet tissues, without the need for any sutures. The scaffold is further shown to offer a sustained release of VEGF, enhancing the migration of endothelial cells in vitro. Histological analyses demonstrate that the administration of the VEGF-eluting GelMA scaffolds that remain adherent to the wound bed significantly improves the quality of healing in porcine wounds. The introduced in vivo printing strategy for wound healing applications is translational and convenient to use in any place, such as an operating room, and does not require expensive bioprinters or imaging modalities

Aerobic Exercise and Scaffolds with Hierarchical Porosity Synergistically Promote Functional Recovery Post Volumetric Muscle Loss

Volumetric muscle loss (VML) is a composite loss of skeletal muscle tissue (greater than 20%) that heals with minimal muscle regeneration, substantial fibrosis, and subsequent functional deficits. Standard treatment, involving free functional muscle transfer and physical therapy, cannot restore full muscle function following VML. Tissue engineered scaffolds, 3D structural templates that mimic native extracellular matrix, are promising to enhance functional muscle formation and recovery. Bioprinted 3D scaffolds are engineered using bioinks, created from scaffolding material, cells, and growth factors, to replicate skeletal muscle architecture with precise control over their spatial deposition. METHODS: The present study evaluates a 3D-printed foam-like scaffold for the treatment of VML in a murine model. This colloidal foam-like scaffold was developed to have high porosity to improve tissue ingrowth, in contrast to dense polymeric scaffolds that routinely resulted in very poor tissue ingrowth, and sufficient stiffness to maintain its shape

Finite element analysis of different fixation methods of screws on absorbable plate for rib fractures

Multiple rib fractures caused by trauma are common injuries and the internal fixation methods of these injuries have been paid more and more attention by surgeons. Absorbable plates and screws are the effective way to treat rib fractures, but there are no reports on which type of screw fixation method is most effective. In this study, finite element analysis was used to study the effects of five different types of screw fixation methods on anterior rib, lateral rib and posterior rib. The finite element model of the ribs was reconstructed from CT images, and the internal pressure (40 kPa) and intercostal force (30 N) on the surfaces of the ribs were simulated accordingly. An intercostal force of 30 N was applied to the upper and lower surfaces of the ribs to simulate the effect of intercostal muscle force. The pressure of 40 kPa was applied to the inner surface of the ribs, and the normal direction was applied to the inner surface of the ribs. The positive direction was considered inspiratory pressure, and the negative direction was considered expiratory pressure. The results indicate the optimal type of screw fixation on the absorbable plate for rib fractures, and provide a basis and reference for clinical application

Natural photothermal-responsive MXene-based antimicrobial nanomaterials Ti3C2/Au NPs for the treatment of deep Staphylococcus aureus-Infected wound

Background: Infection by pathogenic bacteria presents a serious public health issue due to high morbidity and death rates. To aid infective wound closure and healing, a variety of anti-bacterial biomaterials optimized for multiple functions, including drug delivery, biosensing, or tissue engineering, have been designed and manufactured. Methods: Ti3C2 and gold nanoparticles (Au NPs) were chosen as the building blocks for self-assembling biomaterials. The materials were characterized, and then the anti-biofilm and antibacterial properties of Ti3C2/Au NPs against Staphylococcus aureus (S. aureus) were examined. Results: Functionalized Ti3C2/Au NPs demonstrated to kill S. aureus and prevent biofilm development. Ti3C2/Au NPs with a photothermal property may eliminate germs in subcutaneous tissue under photo-irradiation, as demonstrated in the wound healing models and the subcutaneous abscess models. Meanwhile, histological evaluation revealed that Ti3C2/Au NPs may facilitate the conversion of macrophages from the M1 to M2 phenotype, and enhance angiogenesis to providing possible mechanisms by which this dressing fasten the healing of infected wounds. Conclusion: The Ti3C2/Au NPs self-delivery system suggested in this work may thus provide novel materials and techniques for anti-infectious wound treatments

Colloidal multiscale porous adhesive (bio)inks facilitate scaffold integration.

Poor cellular spreading, proliferation, and infiltration, due to the dense biomaterial networks, have limited the success of most thick hydrogel-based scaffolds for tissue regeneration. Here, inspired by whipped cream production widely used in pastries, hydrogel-based foam bioinks are developed for bioprinting of scaffolds. Upon cross-linking, a multiscale and interconnected porous structure, with pores ranging from few to several hundreds of micrometers, is formed within the printed constructs. The effect of the process parameters on the pore size distribution and mechanical and rheological properties of the bioinks is determined. The developed foam bioinks can be easily printed using both conventional and custom-built handheld bioprinters. In addition, the foam inks are adhesive upon in situ cross-linking and are biocompatible. The subcutaneous implantation of scaffolds formed from the engineered foam bioinks showed their rapid integration and vascularization in comparison with their non-porous hydrogel counterparts. In addition, in vivo application of the foam bioink into the non-healing muscle defect of a murine model of volumetric muscle loss resulted in a significant functional recovery and higher muscle forces at 8 weeks post injury compared with non-treated controls

Low mortality oxidative stress murine chronic wound model

Introduction Investigators have struggled to produce a reliable chronic wound model. Recent progress with antioxidant enzyme inhibitors shows promise, but mortality rates are high. We modified the dosage and administration of an antioxidant enzyme inhibitor regimen to reduce mortality while inducing a chronic wound environment.Research design and methods To chemically induce a chronic wound environment, we applied modified doses of catalase (3-amino-1,2,4-triazole; intraperitoneal 0.5 g/kg) and glutathione peroxidase (mercaptosuccinic acid; topical 300 mg/kg) inhibitors to the dorsal wounds of 11-week-old db/db mice. A cohort of these mice was treated with a collagen-glycosaminoglycan scaffold. Both groups were compared with Diabetic control mice.Results This study successfully induced a chronic wound in 11-week-old db/db mice, with no animal deaths. The antioxidant enzyme treated groups showed delayed wound contraction and significantly higher levels of inflammatory tissue, collagen deposition, cellular proliferation and leukocyte infiltration than the Diabetic control group. Angiogenesis was significantly higher in the antioxidant enzyme treated groups, but the vessels were immature and friable. Scaffold engraftment was poor but appeared to promote blood vessel maturation.Conclusions Overall, the two in vivo groups treated with the antioxidant enzyme inhibitors appeared to be arrested in the inflammatory stage of wound healing, while the Diabetic control group progressed to the maturation phase and ultimately remodeling. This model may be instrumental for the development of new wound therapeutics