Leg ulcers: diagnostic approach and management
Robert A. Norman in Geriatric Dermatology, 2020
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.
Biotechnology products and indications I. Proteins
Ronald P. Evens in 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.
Advancing pharmacotherapy for diabetic foot ulcers
Published in Expert Opinion on Pharmacotherapy, 2019
Ioanna Eleftheriadou, Anastasios Tentolouris, Nikolaos Tentolouris, Nikolaos Papanas
After all standard of care has been implemented and a 50% reduction in ulcer size after four weeks has not been achieved, alternative more advanced treatment modalities should be considered [7]. Preliminary results about the effectiveness of heparan sulfate mimetic dressings on diabetic wound healing seem encouraging, although large RCTs are still pending [47]. Sucrose octasulfate dressing application on the other hand was accompanied with very promising results in a recent high quality RCT and its use should be encouraged in patients with non-infected neuro-ischaemic DFUs [48]. Treatment with becaplermin is an FDA approved therapy for the management of DFUs that has been associated with improved healing rates of hard to heal diabetic wounds [49]. PRP is another treatment option, but high quality evidence is lacking so as to recommend its routine use for chronic DFUs [54].
Role of growth factors and biomaterials in wound healing
Published in Artificial Cells, Nanomedicine, and Biotechnology, 2018
Farshad Zarei, Maryam Soleimaninejad
PDGF plays a vital role in each phase of wound healing process. As reported by Trengove et al., PDGF is released from de-granulating platelets following an injury into the wound fluid [34]. PDGF initiates inflammatory response by stimulating mitogenicity and chemotaxis abilities of cells such as neutrophils, macrophages, fibroblasts and smooth muscle cells to the site of the wound [35]. The role of PDGF has been identified during the epithelialization stage of wound healing to up-regulate the production of growth factors such as insulin growth factor (IGF)-1 and thrombospondin-1 and inturn IGF-1 increases the motility of keratinocyte cells and thrombospondin-1 inhibits proteolytic and enzymatic degradation of PDGF [36]. Becaplermin is an FDA rh-PDGF approved drug for the treatment of DFUs and has shown to fast-track the process of wound closure in DFUs in randomized clinical trials (Table 3).
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].
Related Knowledge Centers
- Diabetes
- Diabetic Foot Ulcer
- Skin Cancer
- Cancer
- Erythema
- Atc Code D03
- Topical Gels
- Platelet-Derived Growth Factor
- Boxed Warning