Healing Therapy Research Articles

Strategies to enhance the efficacy of FGF2-based therapies for skin wound healing.

Basic fibroblast growth factor (FGF2 or bFGF) is critical for optimal wound healing. Experimental studies show that local application of FGF2 is a promising therapeutic approach to stimulate tissue regeneration, including for the treatment of chronic wounds that have a low healing potential or are characterised by a pathologically altered healing process. However, the problem of low efficiency of growth factors application due to their rapid loss of biological activity in the aggressive proteolytic environment of the wound remains. Therefore, ways to preserve the efficacy of FGF2 for wound treatment are being actively developed. This review considers the following strategies to improve the effectiveness of FGF2-based therapy: (1) use of vehicles/carriers for delivery and gradual release of FGF2; (2) chemical modification of FGF2 to increase the stability of the molecule; (3) use of genetic constructs encoding FGF2 for de novo synthesis of protein in the wound. In addition, this review discusses FGF2-based therapeutic strategies that are undergoing clinical trials and demonstrating the efficacy of FGF2 for skin wound healing.

Meta-analysis study of small extracellular vesicle nursing application therapies for healing of wounds and skin regeneration.

We designed and performed this meta-analysis to investigate the impact of the application of extracellular small vesicle therapies on regeneration of skin and wound healing. The findings of this study were computed using fixed or random effect models. The mean differences (MDs), and odds ratio (ORs) with their 95% confidence intervals (CIs) were calculated. In this study, 43 publications were included, encompassing 530 animals with artificial wounds. Small extracellular vesicle therapy had a significant greater rate of wound closure (MD, 24.0; 95% CI, 19.98-28.02, P < 0.001), lower scar width (MD, -191.33; 95%CI, -292.26--90.4, P < 0.001), and higher blood vessel density (MD,36.11; 95%CI, 19.02-53.20, P < 0.001) compared to placebo. Our data revealed that small extracellular vesicle therapy had a significantly higher regeneration of skin and healing of wounds based on the results of wound closure rate, lower scar width, and higher blood vessel density compared to placebo. Future studies with larger sample size are needed.

Neuronal regulation of bone and tendon injury repair: a focused review.

Beyond the sensation of pain, peripheral nerves have been shown to play crucial roles in tissue regeneration and repair. As a highly innervated organ, bone can recover from injury without scar formation, making it an interesting model in which to study the role of nerves in tissue regeneration. As a comparison, tendon is a musculoskeletal tissue that is hypo-innervated, with repair often resulting in scar formation. Here, we reviewed the significance of innervation in 3 stages of injury repair (inflammatory, reparative, and remodeling) in 2 commonly injured musculoskeletal tissues: bone and tendon. Based on this focused review, we conclude that peripheral innervation is essential for phases of proper bone and tendon repair, and that nerves may dynamically regulate the repair process through interactions with the injury microenvironment via a variety of neuropeptides or neurotransmitters. A deeper understanding of neuronal regulation of musculoskeletal repair, and the crosstalk between nerves and the musculoskeletal system, will enable the development of future therapies for tissue healing.

A Deep Dive into the Role of Hyperbaric Oxygen Therapy in Enhancing Burn Wound Healing

Burn injuries are a significant cause of admissions to burn and plastic surgery units. One treatment modality for burn injury patients is hyperbaric oxygen therapy (HBOT). HBOT exposes patients to high concentrations of oxygen at increased atmospheric pressure levels. It can enhance burn wound healing by promoting cellular response, inflammatory cytokines, neovascularization, and collagen formation. This review explores the role of HBOT in enhancing burn wound healing, particularly in plastic surgery. We gathered and analyzed information from various web databases, using specific keywords related to burn wound injuries and HBOT. Inclusion criteria encompassed open-access journals and articles relevant to the subject matter. This review revealed that despite some controversial findings and the absence of treatment guidelines for burn patients, HBOT can complement other modalities. Side effects may include neurological and ophthalmic toxicity, as well as mild effects such as nausea and gastrointestinal disturbance. In conclusion, HBOT serves as an adjunctive therapy for promoting wound healing, including in burn patients. Evidence suggests its effectiveness in plastic surgery, potentially reducing hospital stays, costs, and recovery times. Further prospective randomized controlled trials with larger sample sizes and blinding are necessary to address remaining controversies and evaluate the full benefits of HBOT.

Polymeric Nanoparticles for Wound Healing.

Skin injury is one of the most prevalent lesions in humans, and many such wounds, including deep burns and chronic skin wounds, are notoriously difficult to heal. It has been established by medical practitioners that current wound therapies are not perfectly effective and are far from satisfactory. Meanwhile, nanotechnologies have made it possible to develop pharmaceutical formulations that can elevate the effectiveness of conventional pharmacotherapies to entirely new heights. Most nanostructured biomaterials used to treat wounds, including those that have helped establish this fascinating subject, have been polymeric. The bibliographic analysis presented here shows a steady growth in the research output of studies on the use of polymeric nanoparticles in wound healing therapies. This article provides an overview of polymeric nanoparticles for the treatment of wounds with an emphasis on different chemistries and polymer-drug combinations that have been proven the most effective. The wound age, pathophysiology, wound healing treatments of the present and past, as well as the physicochemical nature and methods for the synthesis of polymeric nanoparticles, are all covered in the opening parts of the review. The existing polymeric nano-drug delivery systems with the greatest promise for wound healing and skin regeneration are subsequently addressed and their potentials summarized.

A bibliometric analysis of garlic to improve wound healing

The use of complementary therapies in wound healing continues to grow. One natural ingredient that has many benefits is garlic—however, limited studies have investigated this area of interest. The purpose of the study was to explore the trend of the number of publications, citations, and the journal with the highest number of publications, which field has the most consent to publish, network visualization, overlay visualization, and density visualization on the effect of garlic in wound healing through bibliometric analysis—Bibliometrics analysis used in this study. Records are identified through database searches. Paper restricted in publications years 2018-2023, focus in the field of Health sciences, nursing, public health, clinical sciences and publication type is the article. Data were analyzed using a VOS viewer, and then the analysis was reviewed by co-occurrence and co-authors. Publication searches related to garlic and wound healing yielded 47,351 articles. After screenings through the specified criteria, the number of articles obtained was 12,472. The peak of publications about garlic and wound healing was in 2018. On the other hand, the lowest number was in 2023. Research on the effect of garlic in wound healing is carried out by the fields of medicine, public health or nurses and other fields such as agricultural, vetenary, and food sciences, medical and biomolecular chemistry, pharmacology and pharmaceutical sciences, and medical biotechnology. The peak of publications about precision health and precision medicine was in 2021; the lowest number was in 2023. Research related to the use of garlic has been carried out on acute and diabetic wounds. However, safe concentrations are a concern for more in-depth research on their use in wound care. Keywords: Wound care; wound healing; garlic; bibliometric analysis; nursing research

A Robust Photothermal-Mediated Nanozyme Engineering with Efficient Synergistic Antibacterial Therapy for Wound Healing

A Robust Photothermal-Mediated Nanozyme Engineering with Efficient Synergistic Antibacterial Therapy for Wound Healing

Bidirectionally regulated synthetic ferrocene-based aminal-linked porous organic polymer artificial enzyme towards photothermal-amplified synergistic antibacterial and wound healing therapy

Development of hetero-atom rich porous organic polymers (POPs) in facile and easy accessible methods are of significant importance to broad application potentials and enrich diversity of such materials. Here, a bidirectional adjustment strategy, starting with amino and aldehyde monomers, concurrently, was used for the rational preparation of N-rich aminal-linked POPs with customized structure and function. Five novel ferrocene-based aminal-linked POPs, were facilely fabricated via the one-pot catalyst-free Schiff base polycondensation between the 1,1′-Ferrocene dicarboxaldehyde and different types of triazine-bearing monomers with diverse geometrical features and functions (Porphyrin, cationic viologen, Ferrocene, 1,4,7,10-tetraazacyclododecane, and benzyl). The concurrent introduction of Ferrocene (redox-active) and triazine-Porphyrin (photoactive) endowed remarkable mimicking peroxidase-like activity and excellent photothermal and photodynamic activity with Fc-TDPP, which could be used as a broad spectrum fungicide, exerting photothermal enhanced photodynamic and enzyme antibacterial therapy. Notably, in vitro and in vivo experiments confirmed Fc-TDPP could not only kill S. aureus and E. coli quickly and efficiently, but also significantly accelerate the repairing of open wounds with S. aureus-infection. The as-proposed strategy are available for the low-cost constructing N-rich POPs with specific structure and functions targeted for wide potential applications in various fields.

Self-Healing Guar Gum-Based Nanocomposite Hydrogel Promotes Infected Wound Healing through Photothermal Antibacterial Therapy.

Preventing bacterial infections is a crucial aspect of wound healing. There is an urgent need for multifunctional biomaterials without antibiotics to promote wound healing. In this study, we fabricated a guar gum (GG)-based nanocomposite hydrogel, termed GBTF, which exhibited photothermal antibacterial therapy for infected wound healing. The GBTF hydrogel formed a cross-linked network through dynamic borate/diol interactions between GG and borax, thereby exhibiting simultaneously self-healing, adaptable, and injectable properties. Additionally, tannic acid (TA)/Fe3+ nanocomplexes (NCs) were incorporated into the hydrogel to confer photothermal antibacterial properties. Under the irradiation of an 808 nm near-infrared laser, the TA/Fe3+ NCs in the hydrogel could rapidly generate heat, leading to the disruption of bacterial cell membranes and subsequent bacterial eradication. Furthermore, the hydrogels exhibited good cytocompatibility and hemocompatibility, making them a precandidate for preclinical and clinical applications. Finally, they could significantly promote bacteria-infected wound healing by reducing bacterial viability, accelerating collagen deposition, and promoting epithelial remodeling. Therefore, the multifunctional GBTF hydrogel, which was composed entirely of natural substances including guar gum, borax, and polyphenol/ferric ion NCs, showed great potential for regenerating infected skin wounds in clinical applications.

The Application of Religion as a Method of Drug Rehabilitation for Victims of Drug Abuse at Baitusyifa Rehabilitation Center

Drugs are a complex problem that needs to be resolved, one of the efforts that can be made is to undergo rehabilitation for drug abusers. Drug rehabilitation centers have different methods to achieve their clients' goals in the healing period. Baitusyifa Rehabilitation Center is one of the rehabilitation centers located in Deli Serdang City, North Sumatra which applies religion as a method of drug rehabilitation. The purpose of this study is to describe the religious methods or efforts applied at Baitusyifa Rehabilitation Center. This research uses a qualitative approach. Data were obtained through interviews, observations, and documentation at the research location. Furthermore, the data was analyzed using descriptive qualitative to answer the effectiveness of the application of religion in handling drug abuse clients. The results showed that the application of religion was very influential on clients at Baitusyifa Rehabilitation Center. Clients feel a change for the better and make habits that are carried out in rehabilitation to life after completing the rehabilitation period. Baitusyifa Rehabilitation Center takes an approach by creating self-awareness through study/recitation, changing habits with worship activities such as prayer and murojaah, increasing motivation through reward and punishment models, implementing anonymous letters so that clients evaluate themselves, cupping healing therapy recommended in Islam, and morning exercises to keep clients fit.

Incorporation of Resveratrol-Hydroxypropyl-β-Cyclodextrin Complexes into Hydrogel Formulation for Wound Treatment.

Resveratrol could be applied in wound healing therapies because of its antioxidant, anti-inflammatory and antibacterial effects. However, the main limitation of resveratrol is its low aqueous solubility. In this study, resveratrol was included in hydroxypropyl-β-cyclodextrin complexes and further formulated in Pluronic F-127 hydrogels for wound treatment therapy. IR-spectroscopy and XRD analysis confirmed the successful incorporation of resveratrol into complexes. The wound-healing ability of these complexes was estimated by a scratch assay on fibroblasts, which showed a tendency for improvement of the effect of resveratrol after complexation. The antimicrobial activity of resveratrol in aqueous dispersion and in the complexes was evaluated on methicillin-resistant Staphylococcus aureus (MRSA), Escherichia coli, and Candida albicans strains. The results revealed a twofold decrease in the MIC and stronger inhibition of the metabolic activity of MRSA after treatment with resveratrol in the complexes compared to the suspended drug. Furthermore, the complexes were included in Pluronic hydrogel, which provided efficient drug release and appropriate viscoelastic properties. The formulated hydrogel showed excellent biocompatibility which was confirmed via skin irritation test on rabbits. In conclusion, Pluronic hydrogel containing resveratrol included in hydroxypropyl-β-cyclodextrin complexes is a promising topical formulation for further studies directed at wound therapy.

Update on Chitin and Chitosan from Insects: Sources, Production, Characterization, and Biomedical Applications.

Insects, renowned for their abundant and renewable biomass, stand at the forefront of biomimicry-inspired research and offer promising alternatives for chitin and chitosan production considering mounting environmental concerns and the inherent limitations of conventional sources. This comprehensive review provides a meticulous exploration of the current state of insect-derived chitin and chitosan, focusing on their sources, production methods, characterization, physical and chemical properties, and emerging biomedical applications. Abundant insect sources of chitin and chitosan, from the Lepidoptera, Coleoptera, Orthoptera, Hymenoptera, Diptera, Hemiptera, Dictyoptera, Odonata, and Ephemeroptera orders, were comprehensively summarized. A variety of characterization techniques, including spectroscopy, chromatography, and microscopy, were used to reveal their physical and chemical properties like molecular weight, degree of deacetylation, and crystallinity, laying a solid foundation for their wide application, especially for the biomimetic design process. The examination of insect-derived chitin and chitosan extends into a wide realm of biomedical applications, highlighting their unique advantages in wound healing, tissue engineering, drug delivery, and antimicrobial therapies. Their intrinsic biocompatibility and antimicrobial properties position them as promising candidates for innovative solutions in diverse medical interventions.

Development of alginate and alginate sulfate/polycaprolactone nanoparticles for growth factor delivery in wound healing therapy

Connective tissue growth factor (CTGF) holds great promise for enhancing the wound healing process; however, its clinical application is hindered by its low stability and the challenge of maintaining its effective concentration at the wound site. Herein, we developed novel double-emulsion alginate (Alg) and heparin-mimetic alginate sulfate (AlgSulf)/polycaprolactone (PCL) nanoparticles (NPs) for controlled CTGF delivery to promote accelerated wound healing. The NPs’ physicochemical properties, cytocompatibility, and wound healing activity were assessed on immortalized human keratinocytes (HaCaT), primary human dermal fibroblasts (HDF), and a murine cutaneous wound model. The synthesized NPs had a minimum hydrodynamic size of 200.25 nm. Treatment of HaCaT and HDF cells with Alg and AlgSulf2.0/PCL NPs did not show any toxicity when used at concentrations <50 µg/mL for up to 72 h. Moreover, the NPs’ size was not affected by elevated temperatures, acidic pH, or the presence of a protein-rich medium. The NPs have slow lysozyme-mediated degradation implying that they have an extended tissue retention time. Furthermore, we found that treatment of HaCaT and HDF cells with CTGF-loaded Alg and AlgSulf2.0/PCL NPs, respectively, induced rapid cell migration (76.12% and 79.49%, P<0.05). Finally, in vivo studies showed that CTGF-loaded Alg and AlgSulf2.0/PCL NPs result in the fastest and highest wound closure at the early and late stages of wound healing, respectively (36.49%, P<0.001 on day 1; 90.45%, P<0.05 on day 10), outperforming free CTGF. Double-emulsion NPs based on Alg or AlgSulf represent a viable strategy for delivering heparin-binding GF and other therapeutics, potentially aiding various disease treatments.

Quercetin loaded polymeric dissolving microarray patches: fabrication, characterisation and evaluation

Quercetin, a natural compound, shows promising potential in wound healing by reducing fibrosis, limiting scar formation, and boosting fibroblast proliferation. However, its effectiveness is hindered by poor solubility, resulting in low bioavailability and necessitating high doses for therapeutic efficacy. This study presents a novel approach, fabricating quercetin-loaded microarray patches (MAPs) using widely employed solubility enhancement strategies. Fabricated MAPs exhibited favourable mechanical strength and could be inserted into excised porcine skin to a depth of 650 μm. Furthermore, formulations containing Soluplus® significantly increased the drug loading capacity, achieving up to 2.5 mg per patch and complete dissolution within an hour of application on excised porcine skin. In vitro studies on full-thickness neonatal porcine skin demonstrated that Soluplus®-enhanced MAPs effectively delivered quercetin across various skin layers, achieving a delivery efficiency exceeding 80% over 24 h. Additionally, these prototype MAPs displayed anti-inflammatory properties and demonstrated biocompatibility with human keratinocyte skin cells. Therefore, quercetin-loaded MAPs employing Soluplus® as a solubility enhancer present a promising alternative strategy for wound healing and anti-inflammatory therapy applications.Graphical abstract

A Comprehensive Review of a particular Skin Injury: Pathogenesis, triggers, and current Treatment Options

By definition, an open injury is any severe break in the continuity of the skin and deep tissue. Because contusions are healed injuries, the term given above does not apply to them. The classification of injuries is essential for both therapeutic and medico-legal purposes. Burn injuries are comparable to other injuries in that they require the same basic principles for healing and care, but they differ in that they have a greater impact on the patient's overall health and are essential to the patient's eventual survival, the development of deformity, and rehabilitation. Treatment of burn injuries has always been the responsibility of burn specialists. Both local and systemic therapy have long been advised for treating burn injuries and minimizing burn scars. This review summarizes the treatment of burn injuries brought on by a variety of physical and chemical agents requires unique regimens that are completely different from those used to treat any other traumatic injuries. Other acute injuries that undergo entire blood loss result in shock, but major burns that experience significant plasma loss due to increased capillary permeability result in distress. Burn injuries are initially sterile compared to the majority of other injuries, however, due to the immunocompromised state of burn patients and injury infection frequently ends in death in serious burns. We have discussed the pathophysiology, primary care therapies, nanomaterials used in injury healing therapy and various nanoparticles in injury healing process for burn injuries in this review.

Exploring the potential of bovine colostrum as a bioactive agent in human tissue regeneration: A comprehensive analysis of mechanisms of action and challenges to be overcome.

The study examines bovine colostrum as a potent source of bioactive compounds, particularly growth factors, for tissue regeneration in humans. While previous research has hinted at therapeutic benefits, a comprehensive understanding of its mechanisms remains elusive, necessitating further investigation. This review analyzes nine selected scientific articles on bovine colostrum's bioactive potential in tissue regeneration. In vitro studies highlight its positive impact on cell behavior, including reduced proliferation and induced differentiation. Notably, optimal concentrations and specific colostrum components, such as extracellular vesicles and insoluble milk fat, show more favorable outcomes. In vivo studies underscore bovine colostrum as a promising natural resource for wound healing, despite some studies failing to identify associated benefits. Further research is crucial to unravel the intricate mechanisms, grasp the full potential in regenerative medicine, and develop more effective wound healing therapies. This refined understanding will pave the way for harnessing the complete regenerative potential of bovine colostrum in clinical applications.

MESENCHYMAL STEM CELLS (MSCS) AS A THERAPY FOR CHRONIC WOUND HEALING IN DIABETIC FOOT ULCERS: A REVIEW ARTICLE

Diabetic foot ulcer is a chronic and frequent complication in diabetic patients. Foot ulcers occur in 15-25% of people with diabetes, and most of them require amputation. Conventional treatments for DFU have not been effective enough to reduce the amputation rates. Thus, an effective method to accelerate the healing of diabetic foot ulcers is required. Recently, stem cells have emerged as a promising adjuvant therapy. One of the numerous types of stem cells used in chronic wound healing therapy is Mesenchymal Stem Cells (MSCs). MSCs may be associated with shorter wound healing time, rapid tissue regeneration, and reduced risk of lower limb amputation through all mechanisms. This article summarizes and critically reviews the published literature on the use of MSCs to enhance chronic wound healing in DFUs.

Association of photobiomodulation and antimicrobial photodynamic therapy in healing after multiple extraction in head and neck post-radiotherapy- a case report and literature review

Association of photobiomodulation and antimicrobial photodynamic therapy in healing after multiple extraction in head and neck post-radiotherapy- a case report and literature review

Physical therapy in burn wound healing: Development of clinical prediction rules to identify the efficacy of pulsed electromagnetic therapy

Many studies have demonstrated the effect of pulsed electromagnetic therapy (PEMT) on wound healing. This study aimed to develop a clinical prediction rule (CPR) to assess PEMT's efficacy in burn healing, potentially enhancing treatment decisions and outcomes. It was a one-group intervention study with 46 patients (21 males, 25 females) aged 20 to 55 years, having partial-thickness burns in the first or second healing stage, and a total burned surface area (TBSA) over 15%. The intervention involved pulsed electromagnetic therapy (Fisioline, Italy) for up to six weeks, with 60-minute sessions at 12 Hz and 12 Gauss, three times per week. The statistical analysis was conducted using the SPSS. The study revealed a significant decline in wound surface area (WSA) post-intervention (p &lt; 0.05). A significant negative relationship was found between wound improvement and both age and total body surface area (TBSA) (p &lt; 0.05), while a significant positive relationship was observed between wound improvement and initial wound size (p &lt; 0.05). No significant relationship was found between wound improvement and wound stage (p &gt; 0.05). The study concluded that pulsed electromagnetic therapy significantly reduces wound surface area. Additionally, age, TBSA, and initial burn wound size are important predictors of the therapy's efficacy in treating burn wounds.

The potential role of Hypericum perforatum in wound healing: A literature review on the phytochemicals, pharmacological approaches, and mechanistic perspectives.

St. John's Wort, commonly known as Hypericum perforatum L., is a flowering plant in the Clusiaceae family that traditionally been employed for treating anxiety, depression, wounds, burns, sunburn, irritation, and stomach ailments. This review provides a synopsis of H. perforatum L. phytoconstituents and their biological effects, highlighting its beneficial therapeutic properties for dermatological indications, as well as its antioxidant, antimicrobial, anti-inflammatory, and anti-angiogenic activity in various applications including wound healing and skin conditions such as eczema, sun burn and minor burns also spastic paralysis, stiff neck and mood disorders as anti-depressant and nerve pains such as neuralgia. The data were collected from several databases as Web of Science PubMed, ScienceDirect, Scopus and Google Scholar using the terms: "H. perforatum L.", "H. perforatum L. /phytochemistry," and "H. perforatum extracts/wound healing" collected from 1994 to 2023. The findings suggest H. perforatum L. acts through various mechanisms and plays a role in each phase of the wound healing process, including re-epithelialization, angiogenesis, wound contraction, and connective tissue regeneration. H. perforatum L. enhances collagen deposition, decreases inflammation, inhibits fibroblast migration, and promotes epithelialization by increasing the number of fibroblasts with polygonal shape and the number of collagen fibers within fibroblasts. H. Perforatum L. extracts modulate the immune response and reduce inflammation were found to accelerate the wound healing process via inhibition of inflammatory mediators' production like interleukin-6, tumor necrosis factor-α, cyclooxygenase-2 gene expression, and inducible nitric oxide synthase. Thus, H. perforatum L. represents a potential remedy for a wide range of dermatological problems, owing to its constituents with beneficial therapeutic properties. H. perforatum L. could be utilized in the development of novel wound healing therapies.