Does Probiotic Consumption Enhance Wound Healing? A Systematic Review

The use of probiotics is one of the emerging lines of treatment for wound healing. This systematic review aimed to summarize currently available evidence on the effect of oral or enteral probiotic therapy on skin or oral mucosal wound healing in humans. To verify the developments in this field and the level of available scientific evidence, we applied a broad search strategy with no restrictions on wound type, target population, probiotic strain, or intervention protocol used. This review included seven studies involving 348 individuals. Four studies reported positive outcomes for healing improvement after probiotic therapy, and none of the studies reported adverse effects or a marked increase in wound healing time. The positive or neutral results observed do not generate strong evidence regarding the effectiveness of probiotics for wound healing. However, they suggest a promising field for future clinical research where the probiotic strains used, type of wounds, and target population are controlled for.

Intestinal Mucosal Wound Healing and Barrier Integrity in IBD–Crosstalk and Trafficking of Cellular Players

The intestinal epithelial barrier is carrying out two major functions: restricting the entry of potentially harmful substances while on the other hand allowing the selective passage of nutrients. Thus, an intact epithelial barrier is vital to preserve the integrity of the host and to prevent development of disease. Vice versa, an impaired intestinal epithelial barrier function is a hallmark in the development and perpetuation of inflammatory bowel disease (IBD). Besides a multitude of genetic, molecular and cellular alterations predisposing for or driving barrier dysintegrity in IBD, the appearance of intestinal mucosal wounds is a characteristic event of intestinal inflammation apparently inducing breakdown of the intestinal epithelial barrier. Upon injury, the intestinal mucosa undergoes a wound healing process counteracting this breakdown, which is controlled by complex mechanisms such as epithelial restitution, proliferation and differentiation, but also immune cells like macrophages, granulocytes and lymphocytes. Consequently, the repair of mucosal wounds is dependent on a series of events including coordinated trafficking of immune cells to dedicated sites and complex interactions among the cellular players and other mediators involved. Therefore, a better understanding of the crosstalk between epithelial and immune cells as well as cell trafficking during intestinal wound repair is necessary for the development of improved future therapies. In this review, we summarize current concepts on intestinal mucosal wound healing introducing the main cellular mediators and their interplay as well as their trafficking characteristics, before finally discussing the clinical relevance and translational approaches to therapeutically target this process in a clinical setting.

Identification of the Potential Biomarkers Involved in the Human Oral Mucosal Wound Healing: A Bioinformatic Study

Objective. To identify the key genetic and epigenetic mechanisms involved in the wound healing process after injury of the oral mucosa. Materials and Methods. Gene expression profiling datasets pertaining to rapid wound healing of oral mucosa were identified using the Gene Expression Omnibus (GEO) database. Differential gene expression analysis was performed to identify differentially expressed genes (DEGs) during oral mucosal wound healing. Next, functional enrichment analysis was performed to identify the biological processes (BPs) and signaling pathways relevant to these DEGs. A protein-protein interaction (PPI) network was constructed to identify hub DEGs. Interaction networks were constructed for both miRNA-target DEGs and DEGs-transcription factors. A DEGs-chemical compound interaction network and a miRNA-small molecular interaction network were also constructed. Results. DEGs were found significantly enriched in several signaling pathways including arachidonic acid metabolism, cell cycle, p53, and ECM-receptor interaction. Hub genes, GABARAPL1, GABARAPL2, HDAC5, MAP1LC3A, AURKA, and PLK1, were identified via PPI network analysis. Two miRNAs, miR-34a-5p and miR-335-5p, were identified as pivotal players in the miRNA-target DEGs network. Four transcription factors FOS, PLAU, BCL6, and RORA were found to play key roles in the TFs-DEGs interaction network. Several chemical compounds including Valproic acid, Doxorubicin, Nickel, and tretinoin and small molecular drugs including atorvastatin, 17β-estradiol, curcumin, and vitamin D3 were noted to influence oral mucosa regeneration by regulating the expression of healing-associated DEGs/miRNAs. Conclusion. Genetic and epigenetic mechanisms and specific drugs were identified as significant molecular mechanisms and entities relevant to oral mucosal healing. These may be valuable potential targets for experimental research.

VALIDATION OF HPTM-001, A HUMANIZED CANDIDATE THERAPEUTIC ANTIBODY FOR PROMOTING MUCOSAL WOUND HEALING IN IBD

A hallmark of the clinical course of patients with Inflammatory Bowel Disease (IBD) is poorly healing erosions and ulcers in the intestinal mucosa. Despite the adverse clinical consequences of non-healing mucosal wounds in IBD, current front-line therapies that selectively target mucosal wound healing are not available. Recent studies revealed an association between colonic inflammation and aberrant glycosylation of epithelial CD44v6. Under conditions of inflammation, epithelial CD44v6 was shown to be decorated with the terminal glycan sialyl Lewis A. Importantly, targeting sialylated Lewis glycans on CD44v6 with a murine antibody GM35 was shown to promote mucosal wound healing in cell lines and in biopsy based wounding assays as well as dextran sodium sulfate (DSS) induced murine colitis models. We sequenced CDRs from GM35 and produced a humanized antibody. Eight candidate human IgG1 clones were produced and screened. hPTM-001.4772 was selected from the eight candidates based on glycan affinity and selectivity compared to GM35. In vitro wound healing studies revealed that PTM-001.4772 was as effective as GM35 in promoting repair of scratch wounds with human intestinal epithelial cells. Furthermore, intraperitoneal injection of mice with hPTM-001.4772 during induction of DSS colitis resulted in reduced weight loss compared to control IgG. These results suggest that hPTM-001.4772 is well-positioned as a unique potential candidate therapeutic for IBD that can be used to selectively promote healing of mucosal wounds and ulcers.