Translational research : the journal of laboratory and clinical medicine
-
Although gene therapy has its conceptual origins in the treatment of Mendelian disorders, it has potential applications in regenerative medicine, including bone healing. Research into the use of gene therapy for bone healing began in the 1990s. Prior to this period, the highly osteogenic proteins bone morphogenetic protein (BMP)-2 and -7 were cloned, produced in their recombinant forms and approved for clinical use. ⋯ Data from experiments in small animal models confirm that intralesional delivery of BMP-2 cDNA is able to heal defects efficiently and safely while generating transient, local BMP-2 concentrations 2-3 log orders less than those needed by recombinant BMP-2. The next challenge is to translate this information into a clinically expedient technology for bone healing. Our present research focuses on the use of genetically modified, allografted cells and chemically modified messenger RNA.
-
There is significant interest in understanding the cellular mechanisms responsible for expedited healing response in various oral tissues and how they are impacted by systemic diseases. Depending upon the types of oral tissue, wound healing may occur by predominantly re-eptihelialization, by re-epithelialization with substantial new connective tissue formation, or by a a combination of both plus new bone formation. As a result, the cells involved differ and are impacted by systemic diaseses in various ways. ⋯ In particular, diabetes inhibits the expression of mitogenic growth factors whereas that of pro-inflammatory cytokines is elevated through epigenetic mechanisms. Moreover, hyperglycemia and oxidative stress induced by diabetes prevents the expansion of mesengenic cells that are involved in both soft and hard tissue oral wounds. A better understanding of how diabetes influences the healing processes is crucial for the prevention and treatment of diabetes-associated oral complications.
-
Type 2 diabetes is associated with several potential comorbidities, among them impaired wound healing, chronic ulcerations, and the requirement for lower extremity amputation. Disease-associated abnormal cellular responses, infection, immunological and microvascular dysfunction, and peripheral neuropathy are implicated in the pathogenesis of the wound healing impairment and the diabetic foot ulcer. ⋯ Better understanding of these mechanisms may provide the basis for targeted treatments for chronic diabetic wounds. This review provides an overview of wound healing pathophysiology with a focus on neural involvement in normal and diabetic wound healing, as well as future therapeutic perspectives to address the unmet needs of diabetic patients with chronic wounds.
-
Diabetes mellitus is a costly disease and nearly one-third of these costs are attributed to management of diabetic foot disease including chronic, non-healing, diabetic foot ulcers. Therefore, much effort has been placed into understanding the pathogenesis of diabetic wounds and novel therapeutics. A relatively new area of interest has been macrophage polarization and its role in diabetic wound healing. ⋯ We reviewed factors known to affect macrophage polarization, mostly focused on those that contribute to M2 macrophage polarization, and potential treatments that at least in part target macrophage polarization in the diabetic wound bed. Much of the work has been aimed at reducing hyperglycemia and encouraging pro-inflammatory cytokine neutralization or decreased expression given this has a significant role in producing M1 macrophages. Treatment of diabetic wounds will likely require a multi-modal approach including management of underlying diabetes and control of hyperglycemia, topical therapeutics, and prevention of secondary infection and inflammation.
-
Patients with one of the many chronic inflammatory disorders broadly classified as inflammatory bowel disease (IBD) now have a diverse set of immunomodulatory therapies at their disposal. Despite these recent medical advances, complete sustained remission of disease remains elusive for most patients. The full healing of the damaged intestinal mucosa is the primary goal of all therapies. ⋯ We highlight 3 general approaches that are promising for developing a new class of epithelium-targeted therapies: epithelial stem cells, cytokines, and microbiome engineering. We also provide a frank discussion of some of the challenges that must be overcome for epithelial repair to be therapeutically leveraged. A concerted approach by the field to develop new therapies targeting epithelial wound healing will offer patients a game-changing, complementary class of medications and could dramatically improve outcomes.