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In the burn treatment landscape, a variety of skin substitutes, human tissue-sourced products, and other products are being developed based on tissue engineering (ie, the combination of scaffolds, cells, and biologically active molecules into functional tissue with the goal of restoring, maintaining, or improving damaged tissue or whole organs) to provide dermal replacement, prevent infection, or prevent or mitigate scarring. Skin substitutes can have a variety of compositions (cellular vs acellular), origins (human, animal, or synthetically derived), and complexities (dermal or epidermal only vs composite). The regulation of tissue-engineered products in the United States occurs by one of several pathways established by the U.S. Food and Drug Administration, including a Biologics License Application (BLA), a 510(k) (Class I and Class II devices), Premarket Approval (Class III devices), or a human cells, tissues, and cellular and tissue-based products designation. Key differentiators among these regulatory classifications include the amount and type of data required to support a filing. For example, a BLA requires a clinical trial(s) and evaluation of safety and efficacy by the Center for Biologics Evaluation and Research. Applicable approved biological products must also comply with submission of advertising and promotional materials per regulations. This review provides a description of, and associated requirements for, the various regulatory pathways for the approval or clearance of tissue-engineered products. Some of the regulatory challenges for commercialization of such products for the treatment of burns will be explored. [ABSTRACT FROM AUTHOR]

Topically applied recombinant human platelet-derived growth factor-BB (becaplermin) is a new pharmacologically active therapy for chronic, neuropathic, lower extremity diabetic ulcers. In previous studies, becaplermin gel was administered once daily but dressings were changed twice daily. In the present study of 134 patients with diabetes mellitus and full thickness lower extremity ulcers, dressings were changed only once per day, simplifying the treatment regimen. Efficacy criteria included the percentage of patients achieving complete healing within the 20-week treatment period, the time to achieve complete healing, the rate of ulcer recurrence during the 6-month period following healing, and treatment compliance. Complete healing of ulcers was achieved in 57.5% of patients, with a mean time to closure of 63 days and a recurrence rate of 21% at 6 months. Of the potential factors affecting ulcer healing, only drug compliance (p < 0.001), dressing compliance (p < 0.01), the presence of infection (p < 0.01), baseline ulcer area (p < 0.05), and baseline total wound evaluation score (p < 0.05) were significantly associated with healing. Results of this study further confirm the efficacy and safety of becaplermin gel for the treatment of lower extremity diabetic ulcers. [ABSTRACT FROM AUTHOR]

Pressure ulcers are associated with significant rates of morbidity and mortality, particularly in the geriatric and spinal cord–injured populations. Newer pharmacologically active therapies include the use of topically applied recombinant human platelet‐derived growth factor‐BB (becaplermin), the active ingredient in REGRANEX® (becaplermin) Gel 0.01%, which has been approved in the United States for treatment of lower extremity diabetic neuropathic ulcers that extend into the subcutaneous tissue or beyond and have an adequate blood supply. In this study, the efficacy of becaplermin gel in the treatment of chronic full thickness pressure ulcers was compared with that of placebo gel. A total of 124 adults (≥ 18 years of age) with pressure ulcers were assigned randomly to receive topical treatment with becaplermin gel 100 μg/g (n = 31) or 300 μg/g (n = 32) once daily alternated with placebo gel every 12 hours, becaplermin gel 100 μg/g twice daily (n = 30), or placebo (sodium carboxymethylcellulose) gel (n = 31) twice daily until complete healing was achieved or for 16 weeks. All treatment groups received a standardized regimen of good wound care throughout the study period. Study endpoints were the incidence of complete healing, the incidence of ≥ 90% healing, and the relative ulcer volume at endpoint (endpoint/baseline). Once‐daily treatment of chronic pressure ulcers with becaplermin gel 100 μg/g or 300 μg/g significantly increased the incidences of complete and ≥ 90% healing and significantly reduced the median relative ulcer volume at endpoint compared with that of placebo gel (p < 0.025 for all comparisons). Becaplermin gel 300 μg/g did not result in a significantly greater incidence of healing than that observed with 100 μg/g. Treatment with becaplermin gel was generally well tolerated and the incidence of adverse events was similar among treatment groups. In conclusion, once‐daily application of becaplermin gel is efficacious in the treatment of chronic full thickness pressure ulcers. (WOUND REP REG 1999;7:141–147) --> [ABSTRACT FROM AUTHOR]

Background: Decellularized, dehydrated human amniotic membrane (DDHAM) is an extracellular matrix devoid of cells, cell debris, and growth factors. This study examines the effect of cell attachment to the DDHAM and the induced cellular responses., Materials and Methods: The cell types employed in this study were human dermal fibroblasts (HDF), human epithelial keratinocytes (HEK), and human dermal microvascular endothelial cells (HDMEC), all of which play critical roles in the wound healing process. Further, the DDHAM was compared to a dehydrated human amnion/chorion membrane (dHACM), which contains and releases biological entities including growth factors and cytokines. The HDF and HEK were cultured on the DDHAM and the dHACM, and cell imaging and proliferation assays were performed to evaluate cell attachment to and the ability to proliferate on the DDHAM relative to the dHACM. In addition, the effect of soluble factors released by the DDHAM and the dHACM on cell survival, attachment, and proliferation were examined. The authors also evaluated the effect of soluble factors produced by culturing cells on the DDHAM in in vitro functional assays, including cell survival and endothelial cell migration in a wound closure angiogenesis assay., Results: The HDF and HEK cells readily attached to and proliferated on the DDHAM, while the dHACM did not support cell attachment and proliferation when cultured under the same conditions. Soluble factors secreted when HDF were cultured on the DDHAM enhanced both endothelial cell and keratinocyte survival and endothelial cell migration in a wound closure assay., Conclusions: Although DDHAM is only an extracellular matrix and serves primarily as a scaffold, it has sufficient cues to allow for cell attachment and proliferation. Further, the biological entities released as a consequence of cell attachment promote cell survival and migration.

Unlabelled: While randomized controlled trials (RCTs) are designed to evaluate efficacy and/or safety under controlled conditions, use of strict inclusion/ exclusion criteria are noted to exclude more than 50% of wound populations. Applicability of RCT outcomes to performance expectations in real-world wound populations raises questions about generalizing their results. The primary aim of this decellularized, dehydrated human amniotic membrane (DDHAM) Use Registry Study was to gain experience and observe outcomes with use of a DDHAM in uninfected, full-thickness, or partial-thickness wounds that, in the investigators' opinions, would benefit from such treatment., Methods: Investigators were instructed to provide usual care regarding visit and application frequencies, concomitant therapies, and change in wound-care regimens. The only exclusions were patients with actively infected wounds or known hypersensitivity to DDHAM. Fifteen sites with practicing wound care clinicians of various specialties participated in this review, enrolling chronic wounds including venous, diabetic, pressure, collagen vascular, and arterial ulcers-all of various severities, durations, sizes, and previous treatments. Twenty-eight ulcers studied had failed 32 previous treatments with advanced biologic therapies. A total of 244 wounds were observed in this study, however, this review is limited to the 179 chronic wounds in 165 patients that were enrolled at 15 of the 19 participating centers. The 4 centers that enrolled acute wounds only were excluded., Results: Results from the analysis of this very heterogeneous population demonstrated that during the usual course of an average of 8 weeks of wound management, patients experienced factors that significantly affected wound closure. These factors included wound infections, noncompliance with prescribed treatments (eg, compression, off-loading, and wound care), re-injury of the wound, and systemic comorbidities. Nearly 50% of chronic wounds (including those that failed previous therapy with advanced biologics) with an average baseline area of 3.1 cm2 achieved complete closure within a median of 6.3 weeks without product-related adverse experiences., Conclusion: Despite the challenges of uncontrolled factors that affect healing, this registry study demonstrated the safety and clinical benefit of DDHAM to support wound closure across a variety of chronic wound types and patient conditions in real-world environments.