Gerit Mulder

Treatment of nonhealing diabetic foot ulcers with a platelet-derived growth factor gene-activated matrix (GAM501) : Results of a Phase 1/2 trial

The results from a Phase 1/2 study of a replication‐defective adenovirus encoding human platelet‐derived growth factor (PDGF)‐B formulated in a bovine collagen (Ad‐5PDGF‐B; 2.6% collagen; GAM501) gel for nonhealing neuropathic diabetic foot ulcers is reported. The primary objectives of the study were to evaluate the safety, maximum‐tolerated dose, and preliminary biological activity of GAM501. Fifteen patients enrolled into the study with chronic, nonhealing ulcers received either a single administration of GAM501 at one of three dose levels, or up to four administrations of GAM501 at 1‐week intervals. All patients received standard of care treatment including debridement and were required to wear an off‐loading shoe. GAM501 was found to be safe and well tolerated with no evidence of systemic or local toxicity at all doses so no maximum‐tolerated dose was reached. Serum antibody titers to platelet‐derived growth factor‐B homodimer and collagen were negative and adenoviral DNA was not detected in the blood. In the 12 patients that completed the study, ulcer closure was observed by Month 3 in 10 patients, seven of whom received a single application of GAM501. In conclusion, GAM501 did not appear to have any toxicity at doses that showed biological activity. GAM501 holds promise as a potentially effective treatment for nonhealing diabetic foot ulcers.

Prospective randomized study of the efficacy of hydrogel, hydrocolloid, and saline solution-moistened dressings on the management of pressure ulcers.

A total of 67 patients with pressure ulcers were randomized into one of three treatment modalities: hydrogel sheet dressing, hydrocolloid, or wet‐to‐moist gauze. Safety, efficacy, and physical attributes of the three dressings were evaluated. No statistical significance was found in wound healing rate among the three treatments. Hydrogel sheets were advantageous in allowing wound visualization without dressing or wound disruption.

Enhanced healing of ulcers in patients with diabetes by topical treatment with glycyl-l-histidyl-l-lysine copper

A multicenter, randomized, evaluator‐blinded, placebo‐controlled clinical study was conducted to evaluate the safety and effectiveness of glycyl‐l‐histidyl‐l‐lysine: copper complex (lamin Gel) in the treatment of diabetic neuropathic ulcers. All patients were enrolled in an aggressive standardized wound care protocol consisting of sharp debridement at study entry, daily application of a metered dose of drug, standardized pressure‐relieving footwear, and patient education relating to diabetes control and activity modifications. Treatment with lamin Gel significantly increased the percentage of closure of plantar ulcers (98.5% median area percentage closure compared with 60.8% for vehicle; p < 0.05) and the proportion of patients healing 98% or better. The rate of closure was three times faster with lamin Gel treatment compared with standard care and vehicle. The enhancement of wound closure was more pronounced (median of 89.2% compared with −10.3% for vehicle; p < 0.01) in larger (greater than 100 mm2 initial area at study entry) plantar ulcers caused by the failure of this size of ulcer to respond adequately to standardized wound care treatments in the absence of lamin Gel. Treatment must commence immediately after the initial wound debridement to obtain optimal enhancement of the ulcer closure. The incidence of ulcer infections was significantly lower (7% incidence compared with 34% for vehicle, p < 0.05) in the plantar ulcers treated immediately after debridement with the lamin Gel.

Reduction of Diabetic Foot Ulcer Healing Times Through Use of Advanced Treatment Modalities

Diabetic wounds are a major health care problem associated with delayed healing and high amputation rates. This review systematically evaluated newer wound care therapies for the treatment of diabetic wounds. More recent means of approaching diabetic foot ulcers include various dressings, off-loading shoes, and bioengineered skin constructs and growth factors. Electrical stimulation, phototherapy, electromagnetic fields, and shockwave therapy have been further proposed as potential treatments. A brief overview of these treatments is presented using peer-reviewed evidenced-based literature. A review of the literature demonstrated that treatment of diabetic wounds has focused on either prevention of the wounds in the form of off-loading shoes or adequate protective dressings or on direct treatment of wounds with bioengineered skin constructs, growth factors, or medical devices that accelerate wound healing. The authors’ conclusion, following extensive literature review, is that although excellent national and international guidelines exist regarding suggested approaches to the treatment of the diabetic foot ulcer, there is no definitive or universal consensus on the choice of specific treatment modalities. The importance of optimizing comorbidities and the disease state, hemodynamics, local and peripheral skin and wound care, and metabolic challenges while reducing biological and bacterial burden and minimizing trauma remain the primary approach, followed by choice of the most appropriate treatment material or product.

Regenerative materials that facilitate wound healing.

Wounds and damaged tissue become problematic when the tissue repair process does not proceed in a normal manner. Standard treatment of wounds entails topical dressings and devices in conjunction with good wound care practices. Good practices adequately support healing in most patients. Difficult, chronic, or recalcitrant wounds may require the use of more advanced technologies. Wounds that are full thickness or present with the absence of a matrix, may particularly benefit from regenerative materials. This article focuses on the use of cellular and acellular materials as well as chemical constructs to support granulation, tissue repair, and wound closure.

Comprehensive review of the clinical application of autologous mesenchymal stem cells in the treatment of chronic wounds and diabetic bone healing

Chronic ulcerations are a physical and financial burden to the health and economic establishment in the United States and Worldwide. Improvements in biotechnology and knowledge in stem cell applications have progressed and basic science results are making their way slowly into the clinical arena. Chronic wounds and diabetic bone healing are the key components in the limb salvage of the common diabetic foot. We have examined the current available literature and present the latest on stem cells applications as a novel clinical technique in the treatment of chronic wound and diabetic bone healing and their impact in the treatment paradigm of patients.

Case Presentation: Xenograft Resistance to Protease Degradation in a Vasculitic Ulcer:

Vasculitic ulcers are related to numerous underlying etiologies including autoimmune disease, rheumatoid arthritis and other inflammatory conditions.The resulting ulcerations are associated with high levels of pain, inflammation and tissue necrosis. Current therapies, including surgical intervention, are limited by the underlying inflammatory process and complications secondary to the wound etiology. conservative care has been relatively unsuccessful in promoting wound closure.This case presentations reviews the successful results of using a xenograft in the treatment of an inflammatory ulcer associated with cryoglobulinemia and vasculitis. Product integrity was maintained postoperatively, compared to an allograft, thereby allowing the wound treatment site to progress to closure.The type of cross linkage of acellular grafts may have a direct effect on product stability and treatment outcomes.

Hallux, Sesamoid, and First Metatarsal Injuries

Hallux, sesamoid, and first metatarsal injuries are common foot injuries and have implications in the biomechanical functionality of the first ray and foot. They are essential for propulsion in normal gait. As part of the first ray, it is an important contributor to normal locomotion. Any structure disruption or injury can create angular changes or arthritis, which can have biomechanical implications, including pain, disability, compensation, swelling, and reduced range of motion.

Limb Salvage Surgery and Wound Treatment in the Establishment of Globally Standardized Diabetes, Amputation, and Limb Salvage Centers to Address Lower Extremity Morbidity and Mortality in Thailand

Diabetes and its consequences, particularly diabetic foot ulcerations and amputations, are increasing exponentially on a global level. Universal interest exists in the establishment of educational programs, clinics, and patient materials. However, the availability and skills needed to develop, implement, and consistently manage diabetes and related problems are lacking. This article reviews problems related to care of the diabetic foot, with a focus on Thailand as a model. Recommendations are made to assist with the development and implementation of limb salvage centers for the treatment of the at-risk diabetic foot. The guidelines presented may be applied to any countries where diabetic foot care is in the initial stages of development.