Abstract:Large doses of recombinant growth factors formulated in solution form directly injected into the body is usual clinical practice in treating second-degree scald injuries, with promising results, but this approach creates side effects; furthermore, it may not allow appropriate levels of the factor to be sensed by the target injured tissue/organ in the specific time frame, owing to complications arising from regeneration. In this research, two delivery methods (infusion pumping and local topical application) wer… Show more
“…The hormone erythropoietin (EPO) is another non-growth factor protein that has been shown to increase angiogenesis [140][141][142][143]. In second-degree burn injury model where a substantial portion of the original vasculature is damaged or lost completely, mice and rats treated with topical application or infusion of EPO displayed rates of angiogenesis that were significantly increased over the control that did not receive EPO [140]. Further, wound closure rates in the rats treated with EPO were accelerated over the control, with the wounds on average 98.8% closed by day 7.…”
Section: Non-growth Factor Protein Deliverymentioning
confidence: 99%
“…Accelerates wound healing, promotes keratinocyte migration, increases angiogenesis Mice/Rats [136][137][138] Erythropoietin Delivery increases the rates of neovascularization and increases levels of PECAM-1 + cells at the wound site Mice/Rats [140][141][142][143] hGH Increases re-epithelialization, increases angiogenesis, and increases infiltration of Tlymphocytes Diabetic Rats [325,326] Syndecan-4 Enhances the revascularization, wound closure, and angiogenesis in response to treatment with FGF-2 and PDGF-BB ob/ob Mice/Rats [159] Glypican-1 Increases revascularization in hind limb ischemia model and increases FGF-2 activity in endothelial cells ob/ob Mice [48] SDF-1 Promotes recruitment of endothelial progenitor cells and anti-inflammatory monocytes. Helps to accelerate the wound healing process and promotes bMSC migration to the wound site.…”
The enhancement of wound healing has been a goal of medical practitioners for thousands of years. The development of chronic, non-healing wounds is a persistent medical problem that drives patient morbidity and increases healthcare costs. A key aspect of many non-healing wounds is the reduced presence of vessel growth through the process of angiogenesis. This review surveys the creation of new treatments for healing cutaneous wounds through therapeutic angiogenesis. In particular, we discuss the challenges and advancement that have been made in delivering biologic, pharmaceutical and cell-based therapies as enhancers of wound vascularity and healing.
“…The hormone erythropoietin (EPO) is another non-growth factor protein that has been shown to increase angiogenesis [140][141][142][143]. In second-degree burn injury model where a substantial portion of the original vasculature is damaged or lost completely, mice and rats treated with topical application or infusion of EPO displayed rates of angiogenesis that were significantly increased over the control that did not receive EPO [140]. Further, wound closure rates in the rats treated with EPO were accelerated over the control, with the wounds on average 98.8% closed by day 7.…”
Section: Non-growth Factor Protein Deliverymentioning
confidence: 99%
“…Accelerates wound healing, promotes keratinocyte migration, increases angiogenesis Mice/Rats [136][137][138] Erythropoietin Delivery increases the rates of neovascularization and increases levels of PECAM-1 + cells at the wound site Mice/Rats [140][141][142][143] hGH Increases re-epithelialization, increases angiogenesis, and increases infiltration of Tlymphocytes Diabetic Rats [325,326] Syndecan-4 Enhances the revascularization, wound closure, and angiogenesis in response to treatment with FGF-2 and PDGF-BB ob/ob Mice/Rats [159] Glypican-1 Increases revascularization in hind limb ischemia model and increases FGF-2 activity in endothelial cells ob/ob Mice [48] SDF-1 Promotes recruitment of endothelial progenitor cells and anti-inflammatory monocytes. Helps to accelerate the wound healing process and promotes bMSC migration to the wound site.…”
The enhancement of wound healing has been a goal of medical practitioners for thousands of years. The development of chronic, non-healing wounds is a persistent medical problem that drives patient morbidity and increases healthcare costs. A key aspect of many non-healing wounds is the reduced presence of vessel growth through the process of angiogenesis. This review surveys the creation of new treatments for healing cutaneous wounds through therapeutic angiogenesis. In particular, we discuss the challenges and advancement that have been made in delivering biologic, pharmaceutical and cell-based therapies as enhancers of wound vascularity and healing.
“…The administration of EPO during skin wound healing is most likely based on its cytoprotective, proangiogenic, anti-apoptotic, and anti-inflammatory effects [238]. Re-epithelialization with hair follicle development at the injury site has also been observed in full-thickness burns upon local or systemic EPO administration [239][240][241].…”
Section: Growth Factors Cytokines Hormones and Related Productsmentioning
Cutaneous wound healing in adult mammals is a complex multi-step process involving overlapping stages of blood clot formation, inflammation, re-epithelialization, granulation tissue formation, neovascularization, and remodelling. Re-epithelialization describes the resurfacing of a wound with new epithelium. The cellular and molecular processes involved in the initiation, maintenance, and completion of epithelialization are essential for successful wound closure. A variety of modulators are involved, including growth factors, cytokines, matrix metalloproteinases, cellular receptors, and extracellular matrix components. Here, we focus on cellular mechanisms underlying keratinocyte migration and proliferation during epidermal closure. Inability to re-epithelialize is a clear indicator of chronic non-healing wounds, which fail to proceed through the normal phases of wound healing in an orderly and timely manner. This review summarizes the current knowledge regarding the management and treatment of acute and chronic wounds, with a focus on re-epithelialization, offering some insights into novel future therapies.
“…EPO and EPO-receptor synthesis and its anti-apoptotic, pro-angiogenic, pro- regenerative, anti-inflammatory, immunomodulatory and hypoxia/ischemia protective effects have been described in many tissues and organs ( Brines and Cerami, 2008 ; Minnerup et al, 2009 ; Solling, 2012 ; Günter et al, 2013b ). Previous publications using rodent models have described faster wound healing, higher quality of scars, prevention of secondary burn progression, higher levels of stem cell markers and higher amount of newly formed blood vessels in burn and scalding injuries or other wound models ( Galeano et al, 2006 ; Tobalem et al, 2012 ; Giri et al, 2015 ). The erythropoietic response to EPO is markedly decreased in thermally injured patients ( Still et al, 1995 ).…”
In adult’s burn injuries belong to the top 15 causes of injury. Annually more than a million patients receive specialized treatment. Improving burned patients’ outcomes is still a challenge. Effects of erythropoietin (EPO) are reported to be pro-angiogenic, pro-regenerative, anti-inflammatory, immunomodulatory and hypoxia/ischemia protective. Study objectives were to demonstrate cytoprotective and regenerative effects of EPO in burned patients in terms of improved wound healing, reduced morbidity and mortality. This was a prospective, placebo-controlled, randomized, double-blind trial. The trial was conducted in 13 specialized burn care centers in Germany. Adult Patients with 2b° or 3° burn injuries were included. Patients received state of the art burn care including obligatory split skin graft transplantation. Study medication was EPO or placebo every other day for 21 days. Between 12/08 and 06/14, 116 patients were randomized, 84 received study medication (EPO 45, Placebo 39). Primary endpoint analysis revealed inconclusive results, as only a minority of patients reached the primary endpoint [100% re-epithelialization: EPO: 23% (9/40); Placebo 30% (11/37)]. Several secondary endpoints such as SOFA score (morbidity), EPO level in blood and wound healing onset revealed clinical, and statistically significant results in favor of the EPO group. Adverse Events (AEs) and Severe Adverse Events (SAEs) were in expected ranges; AEs EPO: 80%, (36/45), Placebo: 77%, (30/39); SAEs EPO: 24%, (11/45), Placebo: 24%, (8/39). Out of 84 patients two died, one per group, thus mortality was lower than expected. Results (SOFA score) indicate a lower morbidity of the EPO group, suggesting pro-regenerative effects of EPO in burned patients. Higher EPO levels might influence the faster onset of re-epithelialization in the first 10 days of the treatment. Both effects could reveal new therapeutic options.Clinical Trial Registration: ISRCT Number: ISRCTN95777824 and EudraCT Number: 2006-002886-38, Protocol Number: 0506.
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