Fractional ablative laser therapy for the treatment of severe burn scars: A pilot study of the underlying mechanisms.

Ablative fractional resurfacing is clinically an efficient treatment for burn scar management. The aim of this pilot study was to investigate the poorly understood mechanisms underlying ablative fractional CO2 laser (AFL-CO2) therapy in relation to biomarkers S100 and 11ß-hydroxysteroid dehydrogenase type 1 (11ß-HSD1). S100 stains for Langerhans cells and neuronal cells, potentially representing the pruritus experienced. 11ß-HSD1 catalyses the interconversion of cortisol and cortisone in cells, promoting tissue remodelling. Immunohistochemical analysis of S100 and 11ß-HSD1 protein expression in the dermis and epidermis of the skin was performed on normal skin, before and after AFL-CO2 therapy. Data assessing outcome parameters was collected concurrently with the skin biopsies. 13 patients were treated with AFL-CO2 therapy. Langerhans cells decreased by 39% after 2nd treatment. Neuronal cells were overexpressed before treatment in the scar tissue by 91% but levels returned to that resembling normal skin. 11ß-HSD1 expression in keratinocytes was significantly higher after laser treatment compared to before in scar tissue (p <0.01). No clear correlation was found in dermal fibroblast numbers throughout the treatment course. Whilst the role of the explored mechanisms and their association with clinical outcomes cannot conclusively be stated, this pilot study demonstrates promising trends that encourages investigation into this relationship.

Thermoresponsive and Injectable Hydrogel for Tissue Agnostic Regeneration.

Injectable hydrogels can support the body's innate healing capability by providing a temporary matrix for host cell ingrowth and neovascularization. The clinical adoption of current injectable systems remains low due to their cumbersome preparation requirements, device malfunction, product dislodgment during administration, and uncontrolled biological responses at the treatment site. To address these challenges, a fully synthetic and ready-to-use injectable biomaterial is engineered that forms an adhesive hydrogel that remains at the administration site regardless of defect anatomy. The product elicits a negligible local inflammatory response and fully resorbs into nontoxic components with minimal impact on internal organs. Preclinical animal studies confirm that the engineered hydrogel upregulates the regeneration of both soft and hard tissues by providing a temporary matrix to support host cell ingrowth and neovascularization. In a pilot clinical trial, the engineered hydrogel is successfully administered to a socket site post tooth extraction and forms adhesive hydrogel that stabilizes blood clot and supports soft and hard tissue regeneration. Accordingly, this injectable hydrogel exhibits high therapeutic potential and can be adopted to address multiple unmet needs in different clinical settings.

3-Dimensional mesothelioma spheroids provide closer to natural pathophysiological tumor microenvironment for drug response studies.

Traditional studies using cancer cell lines are often performed on a two-dimensional (2D) cell culture model with a low success rate of translating to Phase I or Phase II clinical studies. In comparison, with the advent of developments three-dimensional (3D) cell culture has been championed as the latest cellular model system that better mimics in vivo conditions and pathological conditions such as cancer. In comparison to biospecimens taken from in vivo tissue, the details of gene expression of 3D culture models are largely undefined, especially in mesothelioma - an aggressive cancer with very limited effective treatment options. In this study, we examined the veracity of the 3D mesothelioma cell culture model to study cell-to-cell interaction, gene expression and drug response from 3D cell culture, and compared them to 2D cell and tumor samples. We confirmed via SEM analysis that 3D cells grown using the spheroid methods expressed highly interconnected cell-to-cell junctions. The 3D spheroids were revealed to be an improved mini-tumor model as indicated by the TEM visualization of cell junctions and microvilli, features not seen in the 2D models. Growing 3D cell models using decellularized lung scaffold provided a platform for cell growth and infiltration for all cell types including primary cell lines. The most time-effective method was growing cells in spheroids using low-adhesive U-bottom plates. However, not every cell type grew into a 3D model using the the other methods of hanging drop or poly-HEMA. Cells grown in 3D showed more resistance to chemotherapeutic drugs, exhibiting reduced apoptosis. 3D cells stained with H&E showed cell-to-cell interactions and internal architecture that better represent that of in vivo patient tumors when compared to 2D cells. IHC staining revealed increased protein expression in 3D spheroids compared to 2D culture. Lastly, cells grown in 3D showed very different microRNA expression when compared to that of 2D counterparts. In conclusion, 3D cell models, regardless of which method is used. Showed a more realistic tumor microenvironment for architecture, gene expression and drug response, when compared to 2D cell models, and thus are superior preclinical cancer models.

Challenges and innovations in treating chronic and acute wound infections: from basic science to clinical practice.

Acute and chronic wound infection has become a major worldwide healthcare burden leading to significantly high morbidity and mortality. The underlying mechanism of infections has been widely investigated by scientist, while standard wound management is routinely been used in general practice. However, strategies for the diagnosis and treatment of wound infections remain a great challenge due to the occurrence of biofilm colonization, delayed healing and drug resistance. In the present review, we summarize the common microorganisms found in acute and chronic wound infections and discuss the challenges from the aspects of clinical diagnosis, non-surgical methods and surgical methods. Moreover, we highlight emerging innovations in the development of antimicrobial peptides, phages, controlled drug delivery, wound dressing materials and herbal medicine, and find that sensitive diagnostics, combined treatment and skin microbiome regulation could be future directions in the treatment of wound infection.

The effects of cross-linking a collagen-elastin dermal template on scaffold bio-stability and degradation.

MatriDerm is a collagen-elastin dermal template that promotes regeneration in full-thickness wound repair. Due to its noncross-linked status, MatriDerm biodegrades quickly in a wound. Facilitating vascularization and dermal repair, it is desirable for MatriDerm to remain present until the wound healing process is complete, optimizing tissue regeneration and reducing wound contraction. The aim of this study was to investigate the effect of cross-linking MatriDerm on its mechanical and biological properties and to enhance its regenerative functionality. MatriDerm was chemically cross-linked and characterized in comparison with noncross-linked MatriDerm. Scaffold properties including surface morphology, protein release and mechanical strength were assessed. Cell-scaffold interaction, cell proliferation and migration were examined using human dermal fibroblasts. Scaffold biodegradation and its impact on wound healing and contraction were studied in a mouse model. Results showed that cross-linked MatriDerm displayed a small reduction in pore size, significantly less protein loss and a threefold increase in tensile strength. A significant increase in fibroblast proliferation and migration was observed in cross-linked MatriDerm with reduced scaffold contraction in vitro. In the mouse model, noncross-linked MatriDerm was almost completely biodegraded after 14 days whereas cross-linked MatriDerm remained intact. No significant difference in wound contraction was found between scaffolds. In conclusion, cross-linked MatriDerm showed a significant increase in stability and strength, enhancing its durability and cell-scaffold interaction. in vivo analysis showed cross-linked MatriDerm had a reduced biodegradation rate with a similar host response. The extended structural integrity of cross-linked MatriDerm could potentially facilitate improved skin tissue regeneration, promoting the formation of a more pliable scar.