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Leg ulcers: diagnostic approach and management
Published in Robert A. Norman, Geriatric Dermatology, 2020
A. I. Rojas, Y. M. Bello, T.J. Phillips
Topical recombinant PDGF or becaplermin hydrogel (REGRANEX®, Ortho-McNeil Pharmaceutical, Raritan, NJ) has been approved by the FDA for the treatment of lower extremity diabetic ulcers in the USA. Multicenter, double blind, placebo-controlled studies have shown increased wound closure of chronic diabetic ulcers (of more than 8 weeks’ duration) after 20 weeks of daily application of becaplermin gel. At week 20 48–50% of patients treated with becaplermin achieved complete healing, compared with 25–35% of patients in the placebo group53,56. Similarly, the becaplermin-treated group showed decreased time to achieve complete wound closure and increased median reduction in wound area when compared with the placebo group. In these studies all the patients had aggressive surgical debridement before treatment and followed good wound practices (moist environment, control of infection and pressure relief) through the study. No difference in wound closure was seen between the control and treatment groups before 8 weeks of treatment, thus response to becaplermin is only expected to occur after 8 weeks of treatment. Becaplermin appears to be a safe therapy, with similar ulcer related adverse events such as cellulitis or osteomyelitis observed in both treatment and placebo groups.
Wound Healing and Tissue Engineering: Physiology of Wound Healing
Published in Armstrong Milton B., Lower extremity Trauma, 2006
Panthaki Zubin J., Okpaku Anire
Topical growth factors have been shown to improve the long-term outcomes of patients with diabetic ulcers and pressure ulcers (6,12). To date, only platelet-derived growth factor has been licensed for use, for treating noninfected foot ulcers up to 5 cm2 in diabetic patients (becaplermin, Regranex). Endogenous platelet-derived growth factors are produced by platelets, monocytes, macrophages, endothelial cells, fibroblasts, or smooth muscle cells (13). Research studies have shown that it may also have some value in lower extremity wounds due to pressure, venous, iatrogenic, and postsurgical etiology (13,14). Table 3 lists the contraindications to the use of Regranex gel (13).
Biotechnology products and indications I. Proteins
Published in Ronald P. Evens, Biotechnology, 2020
Growth factor (GF) proteins number 21, as listed in Table 8.4. These proteins can be divided into two areas: blood cell GFs, also known as colony-stimulating factors (CSFs), and tissue GFs, all of which are ligands to communicate between cells and stimulate new cell outcomes and functions. The CSFs are secreted by specific cells in organs, for example, erythropoietin by the kidney, and stimulate another cell type to produce an effect; in this example, bone marrow erythroid progenitors are stimulated to accelerate their production of red blood cells and correct anemia. All these GFs are produced by rDNA technology. CSF products for leukocytes are available worldwide, that is, filgrastim, pegfilgrastim, and sargramostim in the United States, and also molgramostim, regramostim, lenograstim, and nartograstim in rest of the world. Biosimilar filgrastim products include biograstim, filgrastim-Hexal, nivestim, ratiograstim, and tevagrastim. They all stimulate white blood cell production and limit infectious complications in myeloid-suppressed cancer patients. Two epoetin molecules (epoetin alfa and epoetin beta) stimulate red blood cell production, with two U.S. products available (Epogen and Procrit), along with Eprex, NeoRecormon, Silapo and Epogin in Europe and Asia. Biosimilar products for epoetin alfa are also available, such as Retacrit. Aranesp in the United States and Nespo in Europe are the hyperglycosylated products of epoetin that have extended half-lives and require less frequent dosing. A pegylated form of epoetin alfa has been developed as well to extend the dosing interval. Becaplermin is a tissue GF for the epidermis and is used to accelerate wound healing in diabetic ulcers. The second recombinant tissue GF is palifermin, impacting keratinocytes, and is used to more rapidly resolve the mucositis in cancer patients receiving chemotherapy, radiation therapy, and bone marrow transplants. Bone growth and bone fusion are accelerated with osteogenic protein-1 and platelet derived GF-BB, both GFs. Recently, neurotrophic keratitis has become treatable with a GF, oxervate. Pegylation has been used to create new GFs with longer half-lives and extended duration of action, for example, filgrastim daily is dosed daily for 5–10 d versus peg-filgrastim (Neulasta) in a single dose. Biosimilar products have also been approved for filgratim around the world; Fulphila, Nivestym, Udencya, and Zarxio.
Challenges faced in developing an ideal chronic wound model
Published in Expert Opinion on Drug Discovery, 2023
Mandy Li Ling Tan, Jiah Shin Chin, Leigh Madden, David L. Becker
In relation to chronic wounds, animal models are essential for studying the pathophysiology of these wounds. Importantly, these models serve as testing platforms for the identification of beneficial topical, systemic, and device-based therapeutics. However, the absence of a true chronic wound model in animals has hindered the development of therapeutic compounds. In a Food and Drug Administration (FDA) published guidance for chronic cutaneous ulcers, it has been recognized that there is still a lack of ideal chronic wound models[117]. Despite the success of the diabetic wound models in identifying the therapeutic potential of numerous growth factors, few treatments have received FDA approval for efficacy. Thus far, Becaplermin gel (Regranex®, Smith and Nephew) is the only chronic wound therapeutic to have received FDA approval following completion of human clinical trials[118]. Hence, while diabetic wound models are widely adopted for chronic wound therapeutic testing, their relevance and efficacy for human chronic wounds remains debatable.
Wound dressings as growth factor delivery platforms for chronic wound healing
Published in Expert Opinion on Drug Delivery, 2021
Ovidio Catanzano, Fabiana Quaglia, Joshua S. Boateng
Topical administration of GFs loaded in creams, gels, or ointments is another delivery option widely explored to promote wound healing [51]. Products containing some GFs such as PDGF, EGF, and bFGF are already approved for human use, and they are available on the market as preparations for external application onto wounds (Table 1). The formulation of GFs in a topical delivery system facilitates their therapeutic application in the clinical management of non-healing wounds such as DFUs, by providing a continuous exposure of residual epidermal cells to GFs that can significantly increase the wound healing rate [52]. For example, several randomized clinical trials have shown the ability of Becaplermin (brand name Regranex® Gel), which contains recombinant PDGF, to accelerate wound closure in DFUs and significantly reduce amputations [53–56]. Moreover, pharmacoeconomic studies have reinforced the cost-effectiveness of Becaplermin as an adjunct to proper wound care even if the treatment with this topical gel is expensive and requires frequent dressing changes. Topical formulations of GFs are indicated for external post-traumatic injury, postoperative surgical wounds, burns, venous ulcers, PUs, and DFUs that are recalcitrant to traditional interventions. Clinical evidence showed that topical formulations loaded with GFs could also be used for the enhancement of skin grafts [57].
Up-to-date role of the dehydrated human amnion/chorion membrane (AMNIOFIX) for wound healing
Published in Expert Opinion on Biological Therapy, 2020
Chitang J Joshi, Abbas Hassan, Miguel Carabano, Robert D Galiano
Treatment of chronic wounds and ulcers, especially arising from diabetes or venous insufficiency has been a long evolving process. Advanced novel therapies such as bioengineered skin substitutes (BSS), living skin equivalents (Apligraf and Dermagraft), and wound care technologies such as a topical gel becaplermin (Regranex) have demonstrated accelerated healing in many patients [29]. The dHACM (Amniofix and Epifix) therapy provides a promising alternative in the care of these hard-to-heal wounds. Zelen et al., in 2015 studied 100 patients with chronic diabetic lower extremity ulcers, comparing 12-week clinical outcomes applying Apligraf (BSS), Epifix (dHACM), and Standard Wound Care (SWC). The dHACM group achieved higher complete closure rates at 12 weeks, with shorter mean time-to-heal duration, lower costs, and graft application [19].