Local Insulin Improves Wound Healing: A Systematic Review and Bayesian Network Meta-Analysis.

BACKGROUND: Wounds are a significant health issue, and reliable and safe strategies to promote repair are needed. Clinical trials have demonstrated that local insulin promotes healing in acute and chronic wounds (ie, reductions of 7% to 40% versus placebo). However, the trials' sample sizes have prevented drawing solid conclusions. Furthermore, no analysis has focused on safety concerns (ie, hypoglycemia). Under the hypothesis that local insulin promotes healing through proangiogenic effects and cellular recruitment, the aim of this systematic review and network meta-analysis (NMA) was to assess its safety and relative effectiveness using a Bayesian approach. METHODS: Medline, CENTRAL, Embase, Scopus, LILACS, and gray literature sources were searched for human studies assessing the local use of insulin versus any comparator since inception to October of 2020. Data on glucose changes and adverse events, wound and treatment characteristics, and healing outcomes were extracted, and an NMA was conducted. RESULTS: A total of 949 reports were found, of which 23 ( n = 1240 patients) were included in the NMA. The studies evaluated six different therapies, and most comparisons were against placebo. NMA showed -1.8 mg/dL blood glucose level change with insulin and a lack of reported adverse events. Statistically significant clinical outcomes identified include reduction in wound size (-27%), increased healing rate (23 mm/day), reduction in Pressure Ulcer Scale for Healing scores (-2.7), -10 days to attain complete closure, and an odds ratio of 20 for complete wound closure with insulin use. Likewise, significantly increased neoangiogenesis (+30 vessels/mm 2 ) and granulation tissue (+25%) were also found. CONCLUSION: Local insulin promotes wound healing without significant adverse events.

Use of Infrared Thermal Imaging for Assessing Acute Inflammatory Changes: A Case Series.

Infrared thermal imaging is a non-contact imaging modality that captures the heat emitted by the human body. Thermal regulation or heat load to the different body parts is mainly regulated via blood supply, which is increased during inflammation. The assessment of the body's level of inflammation with pain, erythema and heat is subjective clinical measurement. Infrared imaging can be an objective tool for identifying and following inflammatory and perfusion changes, thereby helping clinicians locate and document the extent of the inflammation as well as monitor the response to treatment. As an example of this, here, we present three clinical cases where the use of thermography aided the assessment of acute inflammatory changes due to trauma, vasodilation, and allergy.

Enhanced Bone Remodeling After Fracture Priming.

The immune system is an active component of bone repair. Mast cells influence the recruitment of macrophages, osteoclasts and blood vessels into the repair tissue. We hypothesized that if mast cells and other immune cells are sensitized to recognize broken bone, they will mount an increased response to subsequent fractures that may be translated into enhanced healing. To test this, we created a bone defect on the left leg of anesthetized mice and 2 weeks later, a second one on the right leg. Bone repair in the right legs was then compared to control mice that underwent the creation of bilateral window bone defects at the same time. Mice were euthanized at 14 and 56 days. Mineralized tissue quantity and morphometric parameters were assessed using micro-CT and histology. The activity of osteoblasts, osteoclasts, vascular endothelial cells, mast cells, and macrophages was evaluated using histochemistry. Our main findings were (1) no significant differences in the amount of bone produced at 14- or 56 days post-operative between groups; (2) mice exposed to subsequent fractures showed significantly better bone morphometric parameters after 56 days post-operative; and (3) significant increases in the content of blood vessels, osteoclasts, and the number of macrophages in the subsequent fracture group. Our results provide strong evidence that a transient increase in the inflammatory state of a healing injury promotes faster bone remodelling and increased neo-angiogenesis. This phenomenon is also characterized by changes in mast cell and macrophage content that translate into more active recruitment of mesenchymal stromal cells.

3D Printed Polyurethane Scaffolds for the Repair of Bone Defects.

Critical-size bone defects are those that will not heal without intervention and can arise secondary to trauma, infection, and surgical resection of tumors. Treatment options are currently limited to filling the defect with autologous bone, of which there is not always an abundant supply, or ceramic pastes that only allow for limited osteo-inductive and -conductive capacity. In this study we investigate the repair of bone defects using a 3D printed LayFomm scaffold. LayFomm is a polymer blend of polyvinyl alcohol (PVA) and polyurethane (PU). It can be printed using the most common method of 3D printing, fused deposition modeling, before being washed in water-based solutions to remove the PVA. This leaves a more compliant, micro-porous PU elastomer. In vitro analysis of dental pulp stem cells seeded onto macro-porous scaffolds showed their ability to adhere, proliferate and form mineralized matrix on the scaffold in the presence of osteogenic media. Subcutaneous implantation of LayFomm in a rat model showed the formation of a vascularized fibrous capsule, but without a chronic inflammatory response. Implantation into a mandibular defect showed significantly increased mineralized tissue production when compared to a currently approved bone putty. While their mechanical properties are insufficient for use in load-bearing defects, these findings are promising for the use of polyurethane scaffolds in craniofacial bone regeneration.