Evaluating the integration and longevity of a novel reconstitutable liquid wound matrix in a murine model

Chronic wounds are one of the most prevalent health conditions worldwide, causing disability and impaired quality of life for those affected, ultimately resulting in a massive global economic burden. Among the many therapeutic options available for the treatment of chronic wounds, injectable extracellular matrix (ECM)-based wound scaffolds are the most suitable option to treat chronic wounds with complex geometries. Unfortunately, commercially available injectable biomaterials come with specific drawbacks. They are scarce, costly, and limited by their delayed integration. To address these limitations, our research group developed a novel injectable ECM-based wound matrix, referred to as MeshFill, for the treatment of a variety of wounds, including those that are further complicated by deep, irregular, and tunnelled wound beds. In this project, we hypothesized that MeshFill rapidly and efficiently integrates with the host tissue upon application, and allows timely cellular infiltration, survival, and proliferation within the matrix to promote wound repair. To address this hypothesis, the following objectives were designed: Objective 1: Evaluate the efficiency of the integration of MeshFill by assessing the host’s inflammatory response to its application and measuring the magnitude of the cellular infiltration into the scaffold. Histological evaluation and immunofluorescence staining and quantification of Vimentin+, CD45+, and CD3+ cells were performed. Objective 2: Evaluate the longevity of MeshFill following sub-dermal implantation in mice. Biotin-labeled MeshFill was followed histologically with immunofluorescence staining. In this experimental study, we compared our results with Integra®Flowable Wound Matrix, an injectable ECM-based matrix that is commercially available for the treatment of tunneling wounds. MeshFill showed early integration with the host tissue, allowing significant cellular infiltration without inducing an adverse host response. Contrarily, Integra®Flowable prompted a dense capsule-like reaction that limited cellular migration into the scaffold during the first 2 weeks. Longevity assessment of MeshFill revealed slow degradation of a single sub-dermal injection over a 4-week period, with no trace of the biotinylated MeshFill detected after 6 weeks. Results gained from this study demonstrate the potential of this wound matrix as an advanced therapeutic alternative for the management of deep tunnelled wounds.Medicine, Faculty ofExperimental Medicine, Division ofMedicine, Department ofGraduat

Evaluating the Biocompatibility of an Injectable Wound Matrix in a Murine Model

(1) Background: Developing a high-quality, injectable biomaterial that is labor-saving, cost-efficient, and patient-ready is highly desirable. Our research group has previously developed a collagen-based injectable scaffold for the treatment of a variety of wounds including wounds with deep and irregular beds. Here, we investigated the biocompatibility of our liquid scaffold in mice and compared the results to a commercially available injectable granular collagen-based product. (2) Methods: Scaffolds were applied in sub-dermal pockets on the dorsum of mice. To examine the interaction between the scaffolds and the host tissue, samples were harvested after 1 and 2 weeks and stained for collagen content using Masson’s Trichrome staining. Immunofluorescence staining and quantification were performed to assess the type and number of cells infiltrating each scaffold. (3) Results: Histological evaluation after 1 and 2 weeks demonstrated early and efficient integration of our liquid scaffold with no evident adverse foreign body reaction. This rapid incorporation was accompanied by significant cellular infiltration of stromal and immune cells into the scaffold when compared to the commercial product (p < 0.01) and the control group (p < 0.05). Contrarily, the commercial scaffold induced a foreign body reaction as it was surrounded by a capsule-like, dense cellular layer during the 2-week period, resulting in delayed integration and hampered cellular infiltration. (4) Conclusion: Results obtained from this study demonstrate the potential use of our liquid scaffold as an advanced injectable wound matrix for the management of skin wounds with complex geometries.Medicine, Faculty ofNon UBCSurgery, Department ofReviewedFacultyResearcherOthe