scholarly journals Laminin heparin-binding peptides promiscuously bind growth factors and enhance diabetic wound healing

2018 ◽  
Author(s):  
Jun Ishihara ◽  
Ako Ishihara ◽  
Kazuto Fukunaga ◽  
Priscilla S. Briquez ◽  
Jeffrey A. Hubbell
Keyword(s):  
Wound Healing ◽  
Growth Factors ◽  
Growth Factor ◽  
Vascular Endothelial Cell ◽  
Diabetic Mouse ◽  
Heparin Binding ◽  
Surface Receptors ◽  
Binding Domains ◽  
Skin Healing

AbstractLaminin, as a key component of the basement membrane extracellular matrix (ECM), regulates tissue morphogenesis. We show that multiple laminin isoforms promiscuously bind to growth factors (GFs) with high affinity, through their heparin binding domains (HBDs) located in the a chain LG domains. Interestingly, these domains also bind to syndecan cell-surface receptors, promoting attachment of fibroblasts and endothelial cells. We next explore application of these multifunctional laminin HBDs in skin healing in the type 2 diabetic mouse. We demonstrate that covalent incorporation of laminin HBDs into fibrin matrix enables the slow-release of GFs. Incorporation of the α33043-3067 laminin HBD significantly enhances in vivo wound-healing efficacy of vascular endothelial cell growth factor (VEGF)-A165 and platelet-derived growth factor (PDGF)-BB, under conditions where the GFs alone in fibrin are inefficacious. This laminin HBD peptide may be clinically useful by improving biomaterials as both GF reservoirs and cell scaffolds, leading to effective tissue regeneration.

scholarly journals PEG grafted chitosan scaffold for dual growth factor delivery for enhanced wound healing

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Amritha Vijayan ◽  
Sabareeswaran A. ◽  
G. S. Vinod Kumar
Keyword(s):  
Wound Healing ◽  
Growth Factors ◽  
Growth Factor ◽  
Treated Group ◽  
Growth Factor Delivery ◽  
Chitosan Scaffold ◽  
Collagen Formation ◽  
Dual Growth Factor Delivery

AbstractApplication of growth factors at wound site has improved the efficiency and quality of healing. Basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF) induce proliferation of various cells in wound healing. Delivery of growth factor from controlled release systems protect it from degradation and also result in sustained delivery of it at the site of injury. The goal of the study was to develop a Polyethylene glycol (PEG) cross-linked cotton-like chitosan scaffold (CS-PEG-H) by freeze-drying method and chemically conjugate heparin to the scaffold to which the growth factors can be electrostatically bound and evaluate its wound healing properties in vitro and in vivo. The growth factor containing scaffolds induced increased proliferation of HaCaT cells, increased neovascularization and collagen formation seen by H and E and Masson’s trichrome staining. Immunohistochemistry was performed using the Ki67 marker which increased proliferation of cells in growth factor containing scaffold treated group. Frequent dressing changes are a major deterrent to proper wound healing. Our system was found to release both VEGF and bFGF in a continuous manner and attained stability after 7 days. Thus our system can maintain therapeutic levels of growth factor at the wound bed thereby avoiding the need for daily applications and frequent dressing changes. Thus, it can be a promising candidate for wound healing.

scholarly journals Advances in surgical applications of growth factors for wound healing

2019 ◽  
Vol 7 ◽  
Author(s):  
Sho Yamakawa ◽  
Kenji Hayashida
Keyword(s):  
Wound Healing ◽  
Growth Factors ◽  
Growth Factor ◽  
Animal Studies ◽  
Healing Process ◽  
Clinical Importance ◽  
Topical Administration ◽  
Wound Management ◽  
Future Research

Abstract Growth factors have recently gained clinical importance for wound management. Application of recombinant growth factors has been shown to mimic cell migration, proliferation, and differentiation in vivo, allowing for external modulation of the healing process. Perioperative drug delivery systems can enhance the biological activity of these growth factors, which have a very short in vivo half-life after topical administration. Although the basic mechanisms of these growth factors are well understood, most have yet to demonstrate a significant impact in animal studies or small-sized clinical trials. In this review, we emphasized currently approved growth factor therapies, including a sustained release system for growth factors, emerging therapies, and future research possibilities combined with surgical procedures. Approaches seeking to understand wound healing at a systemic level are currently ongoing. However, further research and consideration in surgery will be needed to provide definitive confirmation of the efficacy of growth factor therapies for intractable wounds.

scholarly journals VEGF-A, PDGF-BB and HB-EGF engineered for promiscuous super affinity to the extracellular matrix improve wound healing in a model of type 1 diabetes

2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Michael J. V. White ◽  
Priscilla S. Briquez ◽  
David A. V. White ◽  
Jeffrey A. Hubbell
Keyword(s):  
Extracellular Matrix ◽  
Wound Healing ◽  
Growth Factors ◽  
Growth Factor ◽  
Mouse Model ◽  
Triple Therapy ◽  
Nod Mouse ◽  
Heparin Binding ◽  
Healing Wounds

AbstractChronic non-healing wounds, frequently caused by diabetes, lead to lower quality of life, infection, and amputation. These wounds have limited treatment options. We have previously engineered growth factors to bind to exposed extracellular matrix (ECM) in the wound environment using the heparin-binding domain of placental growth factor-2 (PlGF-2123–144), which binds promiscuously to ECM proteins. Here, in the type 1 diabetic (T1D) NOD mouse model, engineered growth factors (eGFs) improved both re-epithelialization and granulation tissue formation. eGFs were even more potent in combination, and the “triple therapy” of vascular endothelial growth factor-A (VEGF-PlGF-2123–144), platelet-derived growth factor-BB (PDGF-BB-PlGF-2123–144), and heparin-binding epidermal growth factor (HB-EGF-PlGF-2123–144) both improved wound healing and remained at the site of administration for significantly longer than wild-type growth factors. In addition, we also found that changes in the cellular milieu of a wound, including changing amounts of M1 macrophages, M2 macrophages and effector T cells, are most predictive of wound-healing success in the NOD mouse model. These results suggest that the triple therapy of VEGF-PlGF-2123–144, PDGF-BB-PlGF-2123–144, and HB-EGF-PlGF-2123–144 may be an effective therapy for chronic non-healing wounds in that occur as a complication of diabetes.

Mesoderm induction by fibroblast growth factor in early Xenopus development

1990 ◽  
Vol 327 (1239) ◽  
pp. 75-84 ◽  
Keyword(s):  
Growth Factors ◽  
Growth Factor ◽  
Marginal Zone ◽  
Mesoderm Induction ◽  
Fibroblast Growth ◽  
Heparin Binding ◽  
Cell Stage ◽  
Animal Pole

In early amphibian development the mesoderm is formed around the equator of the blastula in response to inductive signals from the endoderm. At the time of its formation the mesoderm consists of a large ‘ventral type’ zone and a small ‘organizer’ zone. A screen of candidate substances showed that a small group of heparin binding growth factors (HBGFs) were active as mesoderm inducing agents in vitro . The fibroblast growth factors (aFGF and bFGF) and embryonal carcinoma derived growth factor (ECDGF) all show similar potency and can produce ventral inductions at concentrations above about 100 pM. Single blastula ectoderm cells can be induced and will differentiate in a defined medium to form mesodermal tissues and all inner blastula cells are competent to respond to the factors. Inducing activity can be extracted from Xenopus blastulae and can be purified by heparin affinity chromatography. Antibody neutralization and Western blotting experiments identify this activity as bFGF. The amounts present are small but would be sufficient to evoke ventral inductions in vivo. It is not yet known whether the bFGF is localized to the endoderm, although it is known that inducing activity secreted by endodermal cells can be neutralized by heparin. The competence of ectoderm to respond to FGF rises from about the 128-cell-stage and falls again by the onset of gastrulation. This change is paralleled by a rise and fall of binding of 125I-labelled aFGF. Chemical cross-linking reveals that this binding is attributable to a receptor of molecular mass about 130 kilodaltons (kDa). The receptor is present both in the marginal zone, which responds to the signal in vivo, and in the animal pole region, which is not induced in vivo but which will respond to HBGFs in vitro . In intact embryos we believe that the ventral type mesoderm forms the somites, kidney and other intermediate structures as well as the blood islands of the ventral midline. These intermediate structures are induced as a function of distance from the organizer in a process called ‘dorsalization’. Lithium salts have a dorsalizing effect on whole embryos and also on explants from the ventral marginal zone, causing them to form large blocks of muscle. Lithium will also cause large muscle blocks to form when applied to ectoderm explants together with FGF. It is difficult to extend these results directly to mammalian embryos, but we have shown that the products of the murine int-2 gene and of the human k-fgf genes are active as mesoderm inducing factors.

scholarly journals VEGF-A, PDGF-BB and HB-EGF engineered for promiscuous super affinity to the extracellular matrix improve wound healing in a model of type 1 diabetes

2021 ◽  
Author(s):  
MICHAEL John Victor WHITE ◽  
Priscilla Briquez ◽  
David Andrew Victor White ◽  
Jeffrey Hubbell
Keyword(s):  
Extracellular Matrix ◽  
Wound Healing ◽  
Growth Factors ◽  
Growth Factor ◽  
Mouse Model ◽  
Triple Therapy ◽  
Nod Mouse ◽  
Heparin Binding ◽  
Healing Wounds

Chronic non-healing wounds, frequently caused by diabetes, lead to lower quality of life, infection, and amputation. These wounds have limited treatment options. We have previously engineered growth factors to bind to exposed extracellular matrix (ECM) in the wound environment using the heparin-binding domain of placental growth factor-2 (PlGF-2123-144), which binds promiscuously to ECM proteins. Here, in the type 1 diabetic (T1D) NOD mouse model, engineered growth factors improved both re-epithelialization and granulation tissue formation. Engineered growth factors were even more potent in combination, and the *triple therapy* of vascular endothelial growth factor-A (VEGF-PlGF-2123-144), platelet-derived growth factor-BB (PDGF-BB-PlGF-2123-144), and heparin-binding epidermal-growth factor (EGF-PlGF-2123-144) both improved wound healing and remained at the site of administration for significantly longer than wild-type growth factors. In addition, we also found that changes in the cellular milieu of a wound, including changing amounts of M1 macrophages, M2 macrophages and effector T cells, are most predictive of wound healing success in the NOD mouse model. These results suggest that the triple therapy of VEGF-PlGF-2123-144, PDGF-BB-PlGF-2123-144, and EGF-PlGF-2123-144 may be an effective therapy for chronic non-healing wounds in that occur as a complication of diabetes.

scholarly journals Bilayered Fibrin-Based Electrospun-Sprayed Scaffold Loaded with Platelet Lysate Enhances Wound Healing in a Diabetic Mouse Model

Nanomaterials ◽  
2020 ◽  
Vol 10 (11) ◽  
pp. 2128
Author(s):  
Paola Losi ◽  
Tamer Al Kayal ◽  
Marianna Buscemi ◽  
Ilenia Foffa ◽  
Aida Cavallo ◽  
...  
Keyword(s):  
Wound Healing ◽  
Growth Factors ◽  
Growth Factor ◽  
Phase Inversion ◽  
Diabetic Mouse ◽  
Platelet Lysate ◽  
Inversion Method ◽  
Post Surgery ◽  
Phase Inversion Method

The present study examined the effects of a bilayered fibrin/poly(ether)urethane scaffold loaded with platelet lysate by a combination of electrospinning and spray, phase-inversion method for wound healing. In particular, the poly(ether)urethane layer was obtained using by a spray phase-inversion method and the fibrin fibers network were loaded with platelet lysate by electrospinning. The kinetics release and the bioactivity of growth factors released from platelet lysate-scaffold were investigated by ELISA and cell proliferation test using mouse fibroblasts, respectively. The in-vitro experiments demonstrated that a bilayered fibrin/poly(ether)urethane scaffold loaded with platelet lysate provides a sustained release of bioactive platelet-derived growth factors. The effect of a bilayered fibrin/poly(ether)urethane scaffold loaded with platelet lysate on wound healing in diabetic mouse (db/db) was also investigated. The application of the scaffold on full-thickness skin wounds significantly accelerated wound closure at day 14 post-surgery when compared to scaffold without platelet lysates or commercially available polyurethane film, and at the same level of growth factor-loaded scaffold. Histological analysis demonstrated an increased re-epithelialization and collagen deposition in platelet lysate and growth factor loaded scaffolds. The ability of bilayered fibrin/poly(ether)urethane scaffold loaded with platelet lysate to promote in-vivo wound healing suggests its usefulness in clinical treatment of diabetic ulcers.

scholarly journals The heparin binding domain of von Willebrand factor binds to growth factors and promotes angiogenesis in wound healing

Blood ◽  
2019 ◽  
Vol 133 (24) ◽  
pp. 2559-2569 ◽  
Author(s):  
Jun Ishihara ◽  
Ako Ishihara ◽  
Richard D. Starke ◽  
Claire R. Peghaire ◽  
Koval E. Smith ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Wound Healing ◽  
Growth Factors ◽  
Growth Factor ◽  
Von Willebrand Factor ◽  
Binding Domain ◽  
Heparin Binding ◽  
Heparin Binding Domain ◽  
Von Willebrand ◽  
Willebrand Factor

Abstract During wound healing, the distribution, availability, and signaling of growth factors (GFs) are orchestrated by their binding to extracellular matrix components in the wound microenvironment. Extracellular matrix proteins have been shown to modulate angiogenesis and promote wound healing through GF binding. The hemostatic protein von Willebrand factor (VWF) released by endothelial cells (ECs) in plasma and in the subendothelial matrix has been shown to regulate angiogenesis; this function is relevant to patients in whom VWF deficiency or dysfunction is associated with vascular malformations. Here, we show that VWF deficiency in mice causes delayed wound healing accompanied by decreased angiogenesis and decreased amounts of angiogenic GFs in the wound. We show that in vitro VWF binds to several GFs, including vascular endothelial growth factor-A (VEGF-A) isoforms and platelet-derived growth factor-BB (PDGF-BB), mainly through the heparin-binding domain (HBD) within the VWF A1 domain. VWF also binds to VEGF-A and fibroblast growth factor-2 (FGF-2) in human plasma and colocalizes with VEGF-A in ECs. Incorporation of the VWF A1 HBD into fibrin matrices enables sequestration and slow release of incorporated GFs. In vivo, VWF A1 HBD-functionalized fibrin matrices increased angiogenesis and GF retention in VWF-deficient mice. Treatment of chronic skin wounds in diabetic mice with VEGF-A165 and PDGF-BB incorporated within VWF A1 HBD-functionalized fibrin matrices accelerated wound healing, with increased angiogenesis and smooth muscle cell proliferation. Therefore, the VWF A1 HBD can function as a GF reservoir, leading to effective angiogenesis and tissue regeneration.

scholarly journals Development of stabilized dual growth factor-loaded hyaluronate collagen dressing matrix

2021 ◽  
Vol 12 ◽  
pp. 204173142199975
Author(s):  
Jihyun Kim ◽  
Kyoung-Mi Lee ◽  
Seung Hwan Han ◽  
Eun Ae Ko ◽  
Dong Suk Yoon ◽  
...  
Keyword(s):  
Wound Healing ◽  
Growth Factor ◽  
Type I ◽  
Diabetic Mice ◽  
Patients With Diabetes ◽  
Diabetic Wound Healing ◽  
Epidermal Growth ◽  
Wound Healing Effect ◽  
Growth Factor Production

Patients with diabetes experience impaired growth factor production such as epidermal growth factor (EGF) and basic fibroblast growth factor (bFGF), and they are reportedly involved in wound healing processes. Here, we report dual growth factor-loaded hyaluronate collagen dressing (Dual-HCD) matrix, using different ratios of the concentration of stabilized growth factors—stabilized-EGF (S-EGF) and stabilized-bFGF (S-bFGF). At first, the optimal concentration ratio of S-EGF to S-bFGF in the Dual-HCD matrix is determined to be 1:2 in type I diabetic mice. This Dual-HCD matrix does not cause cytotoxicity and can be used in vivo. The wound-healing effect of this matrix is confirmed in type II diabetic mice. Dual HCD enhances angiogenesis which promotes wound healing and thus, it shows a significantly greater synergistic effect than the HCD matrix loaded with a single growth factor. Overall, we conclude that the Dual-HCD matrix represents an effective therapeutic agent for impaired diabetic wound healing.

scholarly journals Growth Factor Therapy for Parkinson’s Disease: Alternative Delivery Systems

2021 ◽  
pp. 1-7
Author(s):  
Sarah Jarrin ◽  
Abrar Hakami ◽  
Ben Newland ◽  
Eilís Dowd
Keyword(s):  
Parkinson’S Disease ◽  
Gene Therapy ◽  
Parkinson's Disease ◽  
Growth Factors ◽  
Growth Factor ◽  
Ex Vivo ◽  
Brain Regions ◽  
Delivery Systems ◽  
Alternative Delivery

Despite decades of research and billions in global investment, there remains no preventative or curative treatment for any neurodegenerative condition, including Parkinson’s disease (PD). Arguably, the most promising approach for neuroprotection and neurorestoration in PD is using growth factors which can promote the growth and survival of degenerating neurons. However, although neurotrophin therapy may seem like the ideal approach for neurodegenerative disease, the use of growth factors as drugs presents major challenges because of their protein structure which creates serious hurdles related to accessing the brain and specific targeting of affected brain regions. To address these challenges, several different delivery systems have been developed, and two major approaches—direct infusion of the growth factor protein into the target brain region and in vivo gene therapy—have progressed to clinical trials in patients with PD. In addition to these clinically evaluated approaches, a range of other delivery methods are in various degrees of development, each with their own unique potential. This review will give a short overview of some of these alternative delivery systems, with a focus on ex vivo gene therapy and biomaterial-aided protein and gene delivery, and will provide some perspectives on their potential for clinical development and translation.

Sign in / Sign up

Export Citation Format

Share Document