Growth Factors In Wound Healing Research Articles

DNA-Based Nanocarriers for Extended Release of NZ2114 Peptide and Epidermal Growth Factors in Chronic Wound Healing

Chronic wounds, often accompanied by bacterial infection, pose significant clinical challenges. Recognizing this, there has been a growing interest in leveraging nucleic acids as intelligent materials for targeted cargo delivery. Herein, we introduced a pioneering method for encapsulating the anti-S. aureus peptide NZ2114 and epidermal growth factors (EGF) within crosslinked DNA nanomaterials, creating biodegradable and biocompatible antimicrobial agents with high efficacy. Our research validated that the NZ2114-EGF-Gel could exhibit a specific inhibitory effect on S. aureus growth while simultaneously accelerating human dermal fibroblasts’ proliferation. The crosslinked DNA nanostructures demonstrate an enhanced capacity to promote wound therapy rates during in vivo treatment. These findings present a prospective avenue for facilitating therapeutic wound healing.

Unraveling the Significance of Growth Factors (TGF-β, PDGF, KGF, FGF, Pro Collagen, VEGF) in the Dynamic of Wound Healing

The wound healing process is an intricate biological phenomenon that requires various crucial components, including repair cells, proteins, and biological factors. The process of wound healing can be categorized into three interrelated stages: the stage of inflammation, proliferation, and remodeling. Any interruptions during this process can lead to wound healing that deviates from the typical progression. It is crucial to highlight that growth factors have a profoundly influential effect in this particular situation. This study conducts a thorough and analytical literature review to investigate the essential role of growth factors (TGF-β, PDGF, KGF, FGF, Pro Collagen, and VEGF) in wound healing. This study examines the biochemical and molecular mechanisms via which these growth factors impact the wound healing process, including the inflammation, proliferation, and remodeling phases, by analyzing current and authoritative scientific literature. This paper precisely outlines the role of these variables, including the role of the stem cell secretome enriched with growth factors such as TGF-β, PDGF, KGF, FGF, Pro Collagen, VEGF, and exogenous factors, as previously discussed. It explores their impact on tissue regeneration, angiogenesis, and extracellular matrix formation, essential components of the wound healing process. The main objective of this study is to provide a comprehensive summary of the latest research findings, which includes an in-depth analysis of the contributions of stem cell secretomes to wound healing. The findings provide useful insights into potential growth factor-based treatment approaches, highlighting how the components of the stem cell secretome can be leveraged to enhance the wound healing process.

Phosphatidylserine accelerates wound healing and reduces necrosis in the rats: Growth factor activation.

To examine the effect of topical phosphatidylserine (PS) on wound healing factors and tissue necrosis in in vivo models. Topical PS was applied to evaluate aspects of the wound healing process and growth factors production of vascular endothelial growth factors (VEGF) as well a necrosis reduction in the skin flap of rat models. Moreover, phenytoin (PHT) and cyclosporine A (CsA) were used topically as positive control treatments in wound and necrosis models, respectively. Immunohistochemistry (IHC) VEGF, transforming growth factor-β (TGF-β), fibroblast growth factor (FGF) and histopathology were analysed on the wounds of rats. In the necrosis assessment, necrotic areas were determined on photography taken from the back skin of rats. Results indicated that PS topically enhanced significantly (P < 0.05) numbers of fibroblasts and endothelium while inhibiting the neutrophils and macrophages during the 14 days of wound treatment. Moreover, higher values of collagen deposition and epithelialization scores as well as wound recovery percentage (near 80%) were determined significantly (P < 0.05) in the PS group compared with the control. IHC analysis determined that FGF and VEGF cytokine factors were elevated in the wound site by topical PS. Moreover, the necrotic area was significantly (P < 0.05) improved in the PS group. Our experiment indicated that wound improvement and flap survival values in PS treatments were superior to PHT and CsA control groups, respectively. In conclusion, these findings suggest the potential of PS application in the healing of wounds and control of necrosis development after surgery or skin injuries.

The use of intralesional epidermal growth factor in the treatment of diabetic foot ulcers

Aims: The mitogenic and cell protective effects of epidemal growth factor (EGF) in wound healing stimulate the growth, re-covering the surface of the wound area. In this research we tried to elucidate the effectiveness of intradermal EGF application on wound healing in diabetic foot ulcers regarding the fact that EGF can accelerate the formation of skin cover layer on the infected surface, even in relatively ischemic cases.&#x0D; Methods: The data of 68 patients who applied to our institution’s orthopedics and wound care outpatient clinic with the diagnosis of diabetic foot ulcer, who underwent wound care, debridement and follow-up were retrospectively analyzed. All of the patients included in this study were classified as Wagner Stage III and Stage IV diabetic foot ulcers and were followed up with standard wound care. EGF application was initiated if there was not enough bleeding on the wound borders and defect floor after debridement.&#x0D; Results: The rate of patients with 50% or more granulation in the second week of treatment in the groups was 35.7% (n=10) in the standard treatment group, it was 60% (n=24) in the EGF group (p

ROS/pH dual responsive PRP-loaded multifunctional chitosan hydrogels with controlled release of growth factors for skin wound healing

Platelet-rich plasma (PRP) contains a variety of growth factors (GFs) and has been used in the treatment of a variety of diseases, including skin lesions. In particular, PRP with low immunogenicity will be more widely used. However, the explosive release of GFs limits its further application. In order to achieve controlled release of GFs, a multifunctional and reactive oxygen species (ROS)/pH dual responsive hydrogel was developed to load PRP derived from human cord blood for the treatment of skin wound healing. Based on the hydrogen bond and Schiff base interaction, carboxymethyl chitosan (CMCS), oxidized dextran (Odex) and oligomeric procyanidins (OPC) were crosslinked to form CMCS/Odex/OPC/PRP hydrogel with good injectability, self-healing, adhesion, ROS scavenging, antibacterial activity, controlled and sustained release of GFs. In vitro cell experiments suggested that this hydrogel possessed excellent biocompatibility and could promote the proliferation and migration of L929. In vivo healing of full-layer skin wounds further indicated that the prepared hydrogel could regulate inflammation and promote epithelialization, collagen deposition, and angiogenesis. In summary, this present study demonstrates that CMCS/Odex/OPC/PRP hydrogel may serve as a promising multifunctional dressing for skin wound healing.

Hyaluronic acid hydrogel for controlled release of heterobifunctional photocleavable linker-modified epidermal growth factor in wound healing

Peptide and protein drugs, such as epidermal growth factor (EGF), face challenges related to stability and bioavailability. Recently, hydrogels have emerged as promising carriers for these drugs. This study focuses on a light-responsive hydrogel-based drug delivery system for the controlled release of EGF in wound healing. A photocleavable (PC) linker was designed to bind EGF to the hydrogel matrix, enabling UV light-triggered release of EGF. Hydrogels have evolved from drug reservoirs to controlled release systems, and the o-nitrobenzyl-based PC linkers offer selective cleavage under UV irradiation. We used a thiol-ene crosslinked hyaluronic acid (HA) hydrogel matrix modified with the PC-linked EGF. The release of EGF from the HA hydrogel under UV irradiation was evaluated, along with in vitro and in vivo experiments to assess the controlled effect of EGF on wound healing. Our results indicate that the successful development of a light-responsive hydrogel-based system for precise temporal release of EGF enhances the therapeutic potential in wound healing. This study highlights the importance of incorporating stimulus-responsive functionalities into hydrogel-based drug delivery systems to optimize protein drugs in clinical applications.

Efficacy of Concentrated Platelets-Rich Fibrin versus Injectable Platelets Rich Fibrin on Gingival Thickness and Keratinized Tissue Width in Subjects with Thin Gingival Phenotype: Split-Mouth Randomized Clinical Trial

Background: Platelet-rich fibrin (PRF) has regenerative characteristics and is used as an autologous source of growth factors for tissue regeneration and wound healing. Objective: Evaluating the efficacy of C-PRF for increasing gingival thickness (GT) and keratinized tissue width (KTW) in subjects with a thin gingival phenotype in comparison with I-PRF injection. Methods: Ten healthy participants with a thin gingival phenotype (GT ≤ 1.0 mm) were enrolled in this study. The upper and Lower arches of the participant’s mouth were split into two sides, and each side was randomly injected with C-PRF, while the contralateral side was injected with I-PRF. GT and KTW were assessed before the treatment, 1 month later, and 3 months after the last injection session. Results: Inter-group comparison between I-PRF and C-PRF groups revealed a statistically significant difference at the 3 month follow-up visit, with a mean difference between C-PRF and I-PRF of ±1.373 mm and an effect size of 0.200 at p= 0.048. Intra-group comparison was significant for both groups in both arches except for the I-PRF group in the upper arch for KTW, which was non-significant at p= 0.266. Conclusion: In individuals with thin gingival phenotypes, C-PRF injections may influence an increase in both GT and KTW. The results suggest that the application of C-PRF may be beneficial as a non-surgical method for increasing GT and KTW. (ClinicalTrials.gov NCT05615155).

Positive effect of acellular amniotic membrane dressing with immobilized growth factors in skin wound healing.

The human amniotic membrane dressing has been shown to accelerate the wound healing process in the clinic. In this study, heparin was conjugated to a human Acellular Amniotic Membrane (hAAM) to provide affinity binding sites for immobilizing growth factors. To study the acceleration of the wound healing process, we bound epidermal growth factor and fibroblast growth factor 1 to heparinized hAAMs (GF-Hep-hAAMs). The heparinized hAAMs (Hep-hAAMs) were characterized by toluidine blue staining and infrared spectroscopy. The quality control of hAAM was performed by hematoxylin staining, swelling capacity test and biomechanical evaluation. The cytotoxicity, adhesion, and migration in vitro assays of GF-Hep-hAAMs on L-929 fibroblast cells were also studied by MTT assay, scanning electron microscopy, and scratch assay, respectively. Finally, in vivo skin wound healing study was performed to investigate the wound closure rate, re-epithelization, collagen deposition, and formation of new blood vessels. The results showed that GF-Hep-hAAMs enhance the rate of wound closure and epidermal regeneration in BALB/c mice. In conclusion, GF-Hep-hAAMs could accelerate the wound healing process, significantly in the first week.

Multifunctional chitosan/alginate hydrogel incorporated with bioactive glass nanocomposites enabling photothermal and nitric oxide release activities for bacteria-infected wound healing

It is highly desirable to develop novel multifunctional wound dressing materials capable of delivering active molecules capable of resolving bacterial infections and replenishment of appropriate growth factors for bacteria-infected wound healing. Polysaccharides have numerous biomedical benefits and have been widely used to construct biomaterial scaffolds. Herein, multifunctional chitosan/alginate hydrogel decorated with β-cyclodextrin (β-CD) modified polydopamine (PDA)-bioactive glass (BG) nanoparticles (NPs) integrating photothermal performance and nitric-oxide release activities for the treatment of bacterially infected wounds is presented. As the NO precursor N,N′-di-sec-butyl-N,N′-dinitroso-1,4-phenylenediamine (BNN6) encapsulated into the hydrophobic cavity of β-CD on the PDA-coated BG NPs, the resultant NO@CD-PDA/BG NPs, are imparted with the feature of NIR triggered NO release and desired PTT/NO synergetic antibacterial effects. Furthermore, the release of NO, Ca, and Si ions from the NO@CD-PDA/BG NPs, has the benefit of regulating inflammation, promoting fibroblast proliferation, and stimulating angiogenesis. Besides, the chitosan/alginate hydrogel scaffolds provided a suitable microenvironment to accelerate wound healing. By applying the multifunctional chitosan/alginate nanocomposite hydrogel to S. aureus-infected full-thickness skin defect mouse model, the authors demonstrated that chitosan/alginate nanocomposite hydrogel has multiple functions in preventing bacterial infections, accelerating angiogenesis and wound regeneration, indicating promising application in wound healing.

Phenytoin versus Normal Saline Dressings in the Healing of Chronic Diabetic Foot Ulcers: A Longitudinal Study

Introduction: Chronic wounds, especially the non healing type, are among the foremost common conditions encountered by a surgeon. Currently, steady research is being pursued on the creation of fancy and indulgent topical growth factors for wound healing. One such agent is phenytoin which has a stimulatory effect on connective tissue. Several studies were conducted worldwide to study the effect of phenytoin on chronic ulcers. However, such studies are lacking in our geographical area. Aim: To compare the efficacy of topical phenytoin dressings with conventional saline dressings in the healing of chronic Diabetic Foot Ulcers (DFUs), in terms of the surface area of ulcer, granulation tissue formation as a percentage of the surface area of ulcer, duration of hospital stay, and side effects. Materials and Methods: This was a longitudinal study that included 100 patients with chronic DFUs admitted to a tertiary care hospital, in North Andhra Pradesh for a period of 1 year. The study population was divided into two groups based on the patient’s willingness for undergoing topical phenytoin therapy. Patients willing to undergo the topical phenytoin dressing therapy formed the study group (n=50) and those who were not willing were subjected to traditional saline dressings, which formed the control group (n=50). The variables of the surface area of the ulcer, granulation tissue formation as a percentage of the surface area of the ulcer, duration of hospital stay, and side effects of topical phenytoin dressings were compared using Paired, and Unpaired Student’s t-test, and the p-value of &lt;0.05 was considered significant. Results: The mean age in the study group was 53.94 years and in the control group was 55.92 years. The male:female ratio in the study group was 5:1 and in the control group was 3:1. The mean ulcer surface area in the control group was 37.6 cm2 and in the study group was 40.4 cm2 (p-value=0.012). The mean area of granulation tissue formation in the control group was 36.07 cm2±5.7, and in the study group was 39.63 cm2±2.6 of the total ulcer surface area (p-value=0.001). The granulation tissue formation in the control group was 95.93% of the total ulcer surface area, and in the study group was 98.09% of the total ulcer surface area (p-value=0.001). The mean hospital stay in the control group was 31.3±4.2 days and in the study group was 27.8±2.4 days (p-value=0.001). Conclusion: Phenytoin is better alternative dressing agent with lesser side effects for diabetic foot ulcer care.

Injectable Host-Guest supramolecular hydrogel Co-Delivers hydrophobic and hydrophilic agents for enhanced wound healing

Achieving rapid healing of chronic wounds is still highly demanded. In the last few decades, exogenous administration of basic fibroblast growth factor (bFGF) in both clinical and preclinical investigations has proven to be therapeutically effective. However, the adverse wound environment (e.g., increased inflammation) deteriorates the functionality of bFGF. Therefore, improvements of the wound “soil” in addition to the use of bFGF is of importance to future clinical success. To address this issue, we designed an injectable host–guest drug delivery system for the controlled release of the hydrophilic bFGF alongside the hydrophobic anti-inflammatory drug, Pinocembrin (PNCB), to promote effective wound repair. The hydrophobic PNCB was first loaded into Pluronic F127 micelles (PNCB@F127) and then threaded onto bFGF-mixed α-cyclodextrin (α-CD) chains to form the host–guest hydrogel (P/bFGF@F127α-CD). The in vitro and in vivo results demonstrated that P/bFGF@F127α-CD could effectively accelerate wound healing by combining the therapeutic effects of both PNCB and bFGF. The results showed the potential of combining anti-inflammatory drugs with growth factors for wound healing.

Evaluation of wound healing effect of colostrum and curcumin cream in rat excision wound model

Background: Proper wound healing is very crucial for the reconstruction of injured tissues. Compared to the conventional dressings, currently there are many novel biological wound dressings and healing agents containing colostrum which has many advantages. Aim &amp; Objective: This experimental study was done to evaluate the effect of colostrum and curcumin cream dressing and compare it with that of conventional Povidone iodine dressing. Methods: The rats were anesthetized and excision wounds were created. Wounds were then measured with a standard measuring scale on the day of wounding and then subsequently at a time interval of 4 days till day 20, then on alternate days. After tracing the wound area was treated with the Test and Standard drugs on Day 1,4,8,12,16 and 20. The data was then analysed using Chi square, one-way ANOVA and two tailed t test using Graph pad prism software version 5.0. Results: Efficacy of Colostrum 10% &amp;Curcumin 1% cream (test) was equal to that of povidone iodine 10% (standard) cream with respect to wound contraction and wound healing. But, with respect to the rate of wound healing, Colostrum 10% &amp; Curcumin 1% cream treated group was better compared to the povidone iodine 10% cream treated group. Conclusion: Colostrum plus Curcumin cream has shown a better wound healing at a short time span in excisional wound model in rats, when compared to the conventional povidone iodine cream. Thus, the Colostrum plus curcumin cream appear to be an economical and safe alternative to costly therapies like growth factors for wound healing

Growth factors for treating chronic venous leg ulcers: A systematic review and meta-analysis.

Chronic venous leg ulcers (VLU) are wounds that commonly occur due to venous insufficiency. Many growth factors have been introduced over the past two decades to treat VLU. This systematic review and meta-analysis evaluates the impact of growth factor treatments of VLU in comparison to control for complete wound healing, percent reduction in wound area, time to wound healing, and adverse events. A systematic review and meta-analysis of randomised trials was conducted. MEDLINE and EMBASE were searched up to December 2020. Studies were included if they compared a growth factor versus placebo or standard care in patients with VLU. From 1645 articles, 13 trials were included (n= 991). There was a significant difference between any growth factor and placebo in complete wound healing (P= 0.04). Any growth factor compared to placebo significantly increased the likelihood of percent wound reduction by 48.80% (P= <0.00001). There was no difference in overall adverse event rate. Most comparisons have low certainty of evidence according to Grading of Recommendations, Assessment, Development, and Evaluation. This meta-analysis suggests that growth factors have a beneficial effect in complete wound healing of VLU. Growth factors may also increase percent reduction in wound area. The suggestion of benefit for growth factors identified in this review is not a strong one based on the low quality of evidence.

MICRO AND NANOPARTICLES FOR THE DELIVERY OF GROWTH FACTORS IN DIABETIC WOUNDS

Diabetic wound (DW) is one of the leading complications of diabetes patients with a long history. It also puts an economic burden on people recovering from injuries to manage medication. The critical factors in the treatment of DW are infection, inflammation, and low oxygen level. Since these non-healing injuries are linked to the extended recovery process, current treatments are studied only for a short period. The areas covered in this article are an overview of DM, Pathophysiology of DW, stages of wound healing (Hemostasis, Inflammation, Proliferation, Maturation), the role of growth factor in diabetic wound healing, advantages of micro and nanoparticles over other drug delivery systems and micro and nanoparticles for the delivery of growth factors with different studies.

Growth Factors in Wound Healing – A Review

The review is an overview of the features of growth factors involved in cellular signaling mechanisms regulating the wound healing process. Understanding the insights of this mechanism is significant for opening therapeutic and research avenues in wound healing. The review highlights the synergistic functioning of most of the growth factors which would enhance the possibility of these factors being the targets for wound care therapy.The significance of the onset and resolution of inflammation in the healing process is better understood clinically and a range of recombinant growth factors to combat this condition have been identified and used to accelerate healing process.The chemotactic and growth regulating factors act as triggers that take the cellular and biochemical components through the inflammation, proliferation, epithelialization, angiogenesis and tissue remodeling phases. Clinical conditions that create alteration in expression of these factors lead to slow and incomplete healing. The review emphasizes on the clinical use of synthetic and recombinant growth factors whose synergistic effects are remarkable. The review covers the specific signaling mechanisms involved in the regulation of these growth factor expressions, specifically the PI3K/AKT, RAS/MAP and JAK pathways; these could be potential targets for future research expansions in this field.

Single Dose of N-Acetylcysteine in Local Anesthesia Increases Expression of HIF1α, MAPK1, TGFβ1 and Growth Factors in Rat Wound Healing.

In this study, we aimed to investigate the influence of N-acetylcysteine (NAC) on the gene expression profile, neoangiogenesis, neutrophils and macrophages in a rat model of incisional wounds. Before creating wounds on the backs of 24 Sprague–Dawley rats, intradermal injections were made. Lidocaine–epinephrin solutions were supplemented with 0.015%, 0.03% or 0.045% solutions of NAC, or nothing (control group). Scars were harvested on the 3rd, 7th, 14th and 60th day post-surgery. We performed immunohistochemical staining in order to visualize macrophages (anti-CD68), neutrophils (anti-MPO) and newly formed blood vessels (anti-CD31). Additionally, RT-qPCR was used to measure the relative expression of 88 genes involved in the wound healing process. On the 14th day, the number of cells stained with anti-CD68 and anti-CD31 antibodies was significantly larger in the tissues treated with 0.03% NAC compared with the control. Among the selected genes, 52 were upregulated and six were downregulated at different time points. Interestingly, NAC exerted a significant effect on the expression of 45 genes 60 days after its administration. In summation, a 0.03% NAC addition to the pre-incisional anesthetic solution improves neovasculature and increases the macrophages’ concentration at the wound site on the 14th day, as well as altering the expression of numerous genes that are responsible for the regenerative processes.

Multi-Functional Core-Shell Nanofibers for Wound Healing.

Core-shell nanofibers have great potential for bio-medical applications such as wound healing dressings where multiple drugs and growth factors are expected to be delivered at different healing phases. Compared to monoaxial nanofibers, core-shell nanofibers can control the drug release profile easier, providing sustainable and effective drugs and growth factors for wound healing. However, it is challenging to produce core-shell structured nanofibers with a high production rate at low energy consumption. Co-axial centrifugal spinning is an alternative method to address the above limitations to produce core-shell nanofibers effectively. In this study, a co-axial centrifugal spinning device was designed and assembled to produce core-shell nanofibers for controlling the release rate of ibuprofen and hEGF in inflammation and proliferation phases during the wound healing process. Core-shell structured nanofibers were confirmed by TEM. This work demonstrated that the co-axial centrifugal spinning is a high productivity process that can produce materials with a 3D environment mimicking natural tissue scaffold, and the specific drug can be loaded into different layers to control the drug release rate to improve the drug efficiency and promote wound healing.

Experimental Tracheal Replacement: Angiogenesis and Null Apoptosis Promote Stenosis

BackgroundTracheal replacement is a challenge for thoracic surgeons due to stenosis in the trachea-prosthesis anastomosis. We propose that stenosis occurs due to fibrosis as a result of an abnormal healing process, characterized by an increased expression of wound healing growth factors (vascular endothelial growth factor [VEGF], survivin, and CD31), which promote angiogenesis and decrease apoptosis. We analyzed the immunoreactivity of VEGF, survivin, CD31, and caspase-3 in the development of fibrotic stenosis in prosthetic tracheal replacement.MethodsFourteen dogs were operated on group I (n=7) received a 6-ring cervical tracheal segment autograft, while in group II (n=7), a 6-ring segment of the cervical trachea was resected and tracheal continuity was restored with a Dacron prosthesis. The follow-up was 3 months. Immunoreactivity studies for VEGF, survivin, CD31, and caspase-3 were performed. A statistical analysis was done using the Wilcoxon signed rank test.ResultsFour animals in group I were euthanized on the 10th postoperative day due to autograft necrosis. Three animals completed the study without anastomotic stenosis. Moderate expression of VEGF (p=0.038), survivin (p=0.038), and CD31 (p=0.038) was found. All group II animals developed stenosis in the trachea-prosthesis anastomotic sites. Microscopy showed abundant collagen and neovascularization vessels. Statistically significant immunoreactive expression of VEGF (p=0.015), survivin (p=0.017), and CD31 (p=0.011) was observed. No expression of caspase-3 was found.ConclusionWe found a strong correlation between fibrosis in trachea-prosthesis anastomoses and excessive angiogenesis, moderate to intense VEGF, CD31, and survivin expression, and null apoptotic activity. These factors led to uncontrolled collagen production.

The effect of the polyglycolic acid/collagen composite nanofiber scaffold with fibroblast growth factor in wound healing

The effect of the polyglycolic acid/collagen composite nanofiber scaffold with fibroblast growth factor in wound healing

Effect of Electrospun Nanofibers on Diabetic Wound Healing and Epidermal Growth Factor

Diabetic wound, a common complication in patients with diabetes, is difficult to treat because of the long-term consequences of accumulating advanced glycation end products and high glucose levels. Moreover, wound infections occur frequently in diabetes; therefore, developing effective treatments is of great significance for healing diabetic wounds. Electrospun nanofibers have played a favorable role in wound healing, but the efficacy in diabetes is yet to be investigated. This study used mouse models of DW in order to determine the effect of electrospun nanofibers on wound healing. It turned out that electrospun nanofibers increased the healing rate in mice and inhibited levels of inflammatory cytokines, as well as activated epidermal growth factor (EGF). In vitro experiments revealed that the migration and proliferation of human umbilical vein endothelial cells (HUVECs) were enhanced after the intervention. Overall, electrospun nanofibers can improve the healing of diabetic wounds significantly.