Treatment Of Chronic Wounds Research Articles

Assessment of Linear and Cyclic Peptides' Immobilization onto Cross-Linked, Poly(vinyl alcohol)/Cellulose Nanocrystal Nanofibers Electrospun over Quartz Crystal Microbalances with Dissipation Sensors.

Immobilization of peptides onto nanofiber dressings holds significant potential for chronic wound treatment. However, it is necessary to understand the adsorptive capacity of the produced substrates and the binding affinity of the peptides to determine the interface success. This study aims at exploring for the first time the influence of electrospun poly(vinyl alcohol)-based nanofibers on the adsorption of a cyclic peptide, Tiger 17, and of a linear peptide, Pexiganan, using quartz crystal microbalance with dissipation monitoring (QCM-D). PVA fibers reinforced with 0, 10, and 20% w/v cellulose nanocrystals (CNC) were electrospun directly onto QCM-D sensors and, posteriorly, cross-linked by glutaraldehyde vapor. Adsorption levels of Pexiganan were the highest (∼7348 ng/cm2) on C80/20 PVA/CNC electrospun fibers, while the time to achieve equilibrium was the longest (∼235 min). In contrast, the adsorption mass with cyclic Tiger 17 was the highest (∼3428 ng/cm2) on C100/0 PVA, reaching equilibrium after nearly 123 min. In sequential deposition, the combination Tiger 17 + Pexiganan on C100/0 fibers attained the highest number of bound peptide molecules, with ∼55% of Tiger 17 and ∼45% of Pexiganan. Elastic shear modulus data on this peptide sequence, over the C80/20 electrospun mats, reported 220 and 249 kPa for each peptide, respectively, indicating the formation of stable bonds with the surface. The results contributed to the understanding of the immobilization of linear and cyclic peptides, never studied in combination, and their mutual influence on polymeric substrates for engineering potential wound treatment strategies.

Role of secretomes in chronic wound treatment: a review

Living with a chronic wound may prove to be devastating to patients both physically and psychologically. Wound increases economic and society burden due to low healing rate, prolonged hospital treatment, and increased epidemiology worldwide. Therefore, application wound treatment modalities are necessary for patient recovery. However, each modality has their own advantage and limitation. As a newly-founded modality, secretome, which originated from Mesenchymal stem cells (MSCs) plays an important role in chronic wound healing due to its ability in promoting tissue regeneration and self-renewal that supports cell proliferation and migration. However, different therapeutic potentials can arise according to each source of stem cells. This review highlights the importance of secretome as a modality in treating chronic wounds. Secretome types, stem cell origin, and results when applied in vitro and in vivo will also be comprehensively reviewed.

Deciphering the Interlinked CXCR4-Mediated Feedback Loop Among Signaling Pathways in Diabetic Wound Healing

Abstract: Diabetic chronic wounds and amputations are very serious complications of diabetes mellitus (DM) that result from an integration factor, including oxygen deprivation, elevated reactive oxygen species (ROS), reduced angiogenesis, and microbial invasion. These causative factors lead to tenacious wounds in an inflammatory state, which eventually results in tissue aging and necrosis. Wound healing in DM potentially targets C-X-C chemokine receptor type 4 (CXCR4) regulates several signalling pathways. The CXCR4 signalling pathway integrated with phospholipase C (PLC)/protein kinase-C (PKC) Ca2+ pathways, stromal cell-derived factor-1 (SDF-1), and mitogen- activated protein kinases (MAPKs) pathway for enhancing cell chemotaxis, proliferation, and survival. The dysregulated CXCR4 pathway is connected with poor wound healing in DM patients. Therapeutic strategies targeting CXCR4-based molecules such as UCUF-728, UCUF-965, and AMD3100 have been shown to enhance diabetic wound healing by altering miRNA expression, promoting angiogenesis, and accelerating wound closure. This study indicates that CXCR4 participation in various signalling pathways makes it essential for Understanding the healing of diabetic wounds. Using specific compounds to target CXCR4 offers a potentially effective treatment strategy to improve wound healing in diabetes. Our understanding of CXCR4 signalling and its regulation processes will enable us to develop more potent wound care solutions for diabetic chronic wounds. This report concludes that CXCR4's potential therapeutic targeting shows improvements in diabetic wound repair. This review will demonstrate that CXCR4 plays a major role in wound healing through its various signalling pathways. Targeting CXCR4 with certain agonist molecules shows a therapeutic approach to potentially increasing wound healing in diabetes. By enhancing our understanding of the CXCR4 signalling mechanism in future studies, we can develop more potential treatments for chronic diabetic wounds.

PROSPECTIVE DIRECTIONS OF THE DEVELOPMENT OF BIOACTIVE GLASS FIBERS FOR MEDICAL APPLICATION

The urgency of the development and use of glass fibers for the creation of microfiber dressings for the treatment of chronic wounds in combat conditions has been determined. The availability of such materials is especially important in the conditions of hostilities, which are characterized by the need for quick resuscitation of the wounded and the provision of emergency aid on the battlefield. The use of such materials will save life, shorten the rehabilitation period, and speed up the recovery of the military and civilian population. An analysis of the scientific and technical literature on the composition and properties of bioactive glass fibers for medical use was carried out. The compositions and properties of glass fibers for various purposes were analyzed and their possibility of use in the development of bioactive glass fibers for medical use was established. The selection of the compositions of bioactive glass fibers with a prolonged biocidal effect for the rapid healing of wounds and the restoration of bone tissue is substantiated. The mechanism of action of biocidal components and boron ions in the composition of bioglasses on the ability to inhibit the negative effects of pathogenic microorganisms was analyzed. The use of boroaluminophosphate glass fibers for the manufacture of effective dressings for the treatment of wounds in crisis situations in combat conditions will increase the percentage of survival and reduce the duration of treatment due to the direct action of cations and anions of the materials in vivo. The main theoretical principles of the creation of bioactive boroaluminophosphate glass fibers, modified with group II metal cations, which will be characterized by the presence of a strengthened surface layer, and characterized at the same time by high biocompatibility, biocide with prolonged action and non-toxicity, have been determined. The introduction of domestically developed bioactive glass fibers into medical practice will significantly increase the competitiveness of domestic medical materials, as well as ensure defense capability and safety, and contribute to the stabilization of the market in the conditions of sustainable development of the state.

Study on Healing Treatment of Chronic Wound

Study on Healing Treatment of Chronic Wound

Wound Gel Formulations Containing Poloxamer 407 and Polyhexanide Have In Vitro Antimicrobial and Antibiofilm Activity Against Wound-Associated Microbial Pathogens.

Chronic wounds are often caused or exacerbated by microbial biofilms that are highly resistant to antimicrobial treatments and that prevent healing. This study compared the antimicrobial and antibiofilm activity of nine topical wound treatments, comprising gels with different concentrations of poloxamer 407 (20-26%) and different pH levels (4-6) and containing polyhexanide (PHMB) as an antimicrobial agent; the effects of pH on wound gels containing this agent have not been previously reported. The wound gel formulations were tested against six common wound-associated microbial pathogens: Staphylococcus aureus, S. epidermidis, Pseudomonas aeruginosa, Escherichia coli, Acinetobacter baumannii, and Candida albicans. Time-kill assays were used to assess antimicrobial activity against planktonic forms of each species, and a colony biofilm model was used to assess antibiofilm activity against existing biofilms as well as inhibition of new biofilm formation. Biofilm inhibition activity was also assessed in the presence of common wound dressing materials. Wound gels with higher pH levels exhibited stronger antimicrobial activity, while poloxamer 407 concentrations >20% negatively impacted antimicrobial activity. Wound gel formulations were identified that had antimicrobial, antibiofilm, and biofilm inhibition activity against all tested species in vitro. Biofilm inhibition activity was not affected by contact with common wound dressings. Further development of these wound gels may provide a valuable new option for the treatment and prevention of chronic wounds.

Gallic acid functionalized silk fibroin/gelatin composite wound dressing for enhanced wound healing

As the incidence of chronic wounds increases, the requirements for wound dressings are rising. The specific aim of this study is to propose a novel gallic acid (GA) functionalized silk fibroin (SF) and gelatin (Gel) composite wound dressing in which GA is used as an antibacterial and wound healing substance. Via electrospinning, SF, Gel, and GA mixed solutions could be conveniently fabricated into a composite nanofiber mat (SF-Gel-GA), consisting of uniform fibers with an average diameter around 134.57 ± 84 nm. The internal mesh structure of SF-Gel-GA provides sufficient drug loading capacity, proper moisture permeability, and proper degradation rate. SF-Gel-GA presents excellent biocompatibility. NIH-3T3 fibroblast cells could adhere and spread stably on the SF-Gel-GA surface with slightly promoted proliferation. In the presence of SF-Gel-GA, the growth of both Gram-positive and Gram-negative bacteria, includingStaphylococcus aureusandPseudomonas aeruginosa, is significantly inhibited in both plate and suspension cultures. A cutaneous excisional mouse wound model proves the efficient ability of SF-Gel-GA to promote wound healing. Compared with pure SF dressing and commercial Tegaderm Hydrocolloid3Mdressing, the wound closure rate with SF-Gel-GA treatment is significantly improved. The histological assessments further demonstrate SF-Gel-GA could facilitate collagen deposition, neovascularization, and epithelialization at wound sites to promote wound healing. In conclusion, a novel SF-Gel-GA composite wound dressing with efficient wound healing activities have been developed for chronic wound treatment with broad healing potential.

Multifunctional Dual Nano-MOF-Modified Decellularized Small Intestinal Submucosa Membrane Accelerates Healing of Infected Wound.

The treatment of complex or chronic skin wounds caused by burns, trauma, surgery, and genetic disorders has been a worldwide challenge. Small intestinal submucosa (SIS) is a biological material that is widely used in wound healing. How to further expand the wound healing application of SIS, especially in repairing infected wounds, remains a hot research topic for many tissue engineering and biomaterial scholars focusing on skin regeneration. This study uses nanometal-organic frameworks (nano-MOFs), which have not been applied to modify the SIS membrane before, to construct multifunctional dual nano-MOFs @ SIS membrane (dnMOF@SISm). Nano-MOFs are functionalized onto the nanofiber of SIS via in situ self-assembly under mild reaction conditions without any toxic reagent or complex instruments. The dnMOF@SISm can release Co2+, Zn2+, and bioactive factors, participating in the whole stage of the repair of infected wounds. In vitro, it can regulate the biological activities of various functional cells such as fibroblasts, endothelial cells, and macrophages and shows good antibacterial ability. In the infected full-thickness skin defect rat model, dnMOF@SISm can release metal ions and ligands, killing pathogenic bacteria colonized on the wound surface at the first stage, and then trigger and accelerate the skin repair process via angiogenesis, immune regulation, and collagen deposition. Above all, an efficient, nontoxic, mild self-assembly strategy realizes the functionalization of dual nano-MOFs on the nanofiber of SIS to expand its clinical application scenarios, especially in infected wounds.

Cord Blood Platelet Lysate-Loaded Thermo-Sensitive Hydrogels for Potential Treatment of Chronic Skin Wounds.

Chronic skin wounds (CSWs) are a worldwide healthcare problem with relevant impacts on both patients and healthcare systems. In this context, innovative treatments are needed to improve tissue repair and patient recovery and quality of life. Cord blood platelet lysate (CB-PL) holds great promise in CSW treatment thanks to its high growth factors and signal molecule content. In this work, thermo-sensitive hydrogels based on an amphiphilic poly(ether urethane) (PEU) were developed as CB-PL carriers for CSW treatment. A Poloxamer 407®-based PEU was solubilized in aqueous medium (10 and 15% w/v) and added with CB-PL at a final concentration of 20% v/v. Hydrogels were characterized for their gelation potential, rheological properties, and swelling/dissolution behavior in a watery environment. CB-PL release was also tested, and the bioactivity of released CB-PL was evaluated through cell viability, proliferation, and migration assays. PEU aqueous solutions with concentrations in the range 10-15% w/v exhibited quick (within a few minutes) sol-to-gel transition at around 30-37 °C and rheological properties modulated by the PEU concentration. Moreover, CB-PL loading within the gels did not affect the overall gel properties. Stability in aqueous media was dependent on the PEU concentration, and payload release was completed between 7 and 14 days depending on the polymer content. The CB-PL-loaded hydrogels also showed biocompatibility and released CB-PL induced keratinocyte migration and proliferation, with scratch wound recovery similar to the positive control (i.e., CB-PL alone). The developed hydrogels represent promising tools for CSW treatment, with tunable gelation properties and residence time and the ability to encapsulate and deliver active biomolecules with sustained and controlled kinetics.

Maggots in Medicine: A Narrative Review Discussing the Barriers to Maggot Debridement Therapy and Its Utilisation in the Treatment of Chronic Wounds.

Background: There is currently no standardised guidance that supports any particular method of debridement. Maggot debridement therapy (MDT) is often used as a last-resort therapy over more conventional treatments, despite mounting evidence of its benefits. Objectives: This review aimed to critically analyse the systemic and individual barriers to MDT implementation and utilisation. As the primary providers of wound care, discussions are primarily focused on nursing care. Search strategy: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) was used to conduct a literature search of the studies published between 2012 and 2022 across four databases: CINAHL, Cochrane, British Nursing Index and PubMed. The keywords used for this search were based on the PICO (Population, Intervention, Comparison, Outcome) framework. Twenty-three main articles met the inclusion criteria. All the studies were quality appraised using a risk of bias tool and data were extracted using a predesigned form. The evidence base of the four main themes were discussed: (1) effectiveness of MDT compared to conventional treatments, (2) perceptions and stigma, (3) cost, training and accessibility and (4) side-effects. Conclusions: The findings of this review suggest that MDT is an underused and potentially very effective method of debridement compared to conventional treatments. The identified barriers could be mitigated with relatively low-cost solutions. More high-quality research is needed across all the barriers.

The Effectiveness of the Combined Therapy in the Treatment of Chronic Non-Healing Wounds in Patients with Autoimmune Diseases

ObjectiveAutoimmune diseases are systemic conditions that can have negative effects on wound healing. The objective of the present study was to investigate the efficacy of combining bone marrow-derived mesenchymal stem cells (BM-MSCs), acellular dermal matrix (ADM), split-thickness skin graft (STSG), and negative-pressure wound therapy (NPWT) in the treatment of patients with autoimmune diseases and chronic non-healing wounds. MethodsThirty four patients with autoimmune diseases and non-healing chronic wounds of the lower extremities between 2012 and 2023 were included in the study. Among these, eighteen patients had Behçet’s disease, eight patients had polyarteritis nodosa, and eight patients had systemic lupus erythematosus. All patients underwent split-thickness skin grafting in external centers. The wounds were debrided, and BM-MSCs concentrate was injected into the wound base. A suitable ADM was applied to the wound. STSG were adapted onto the ADM. The grafts were closed with NPWT. ResultsPatients were followed up for an average of 1.2 years. No necrosis was observed at the wound sites of the postoperative patients. During the long-term follow-up, no wounds were observed at the same sites. ConclusionAlthough autoimmune diseases fall within the scope of rheumatology, the treatment of chronic non-healing wounds that accompany such diseases requires a multidisciplinary approach. We demonstrated that the combined use of BM-MSCs, ADM, STSG, and NPWT presents an effective approach in the healing of these types of wounds.

Biodegradable Oxygen‐Generating Microneedle Patches for Regenerative Medicine Applications

Upon injury, regenerating skin is metabolically active and requires oxygen for physiological processes related to wound healing. Such processes can be halted in hypoxic conditions common in chronic wounds. Microneedle arrays (MNAs) have been demonstrated to improve therapeutic delivery and wound healing. Recently, few studies have explored the use of oxygen‐releasing MNAs; however, they involve complex manufacturing and handling and fail to eliminate cytotoxic byproducts. To address these challenges, biodegradable and mechanically robust gelatin methacryloyl‐based MNAs are developed that can penetrate the tissue and release oxygen upon exposure to interstitial fluid and wound exudates. The oxygen release rate and biocompatibility of the developed MNAs with different compositions are evaluated and optimized. Interestingly, in vitro studies demonstrate that the optimized compositions can release oxygen at therapeutic levels and significantly increase viability of chronically hypoxic cells to match that of normoxic cells. In vivo studies further confirm that the optimized oxygen‐generating MNAs do not cause any harm or impair healing in a murine model of acute skin injury. Additionally, transcriptomic analysis reveals upregulation of key pathways related to fibroblast motility, lipid metabolism, and a marked reduction in inflammatory signaling, all of which contribute to improved wound healing. The developed strategy can introduce new opportunities in elimination of hypoxia and therefore treatment of chronic wounds.

Plant-Derived Exosome-Like Nanovesicles in Chronic Wound Healing.

The incidence of chronic wounds is steadily increasing each year, yet conventional treatments for chronic wounds yield unsatisfactory results. The delayed healing of chronic wounds significantly affects patient quality of life, placing a heavy burden on patients, their families, and the healthcare system. Therefore, there is an urgent need to find new treatment methods for chronic wounds. Plant-derived exosome-like nanovesicles (PELNs) may be able to accelerate chronic wound healing. PELNs possess advantages such as good accessibility (due in part to high isolation yields), low immunogenicity, and good stability. Currently, there are limited reports regarding the role of PELNs in chronic wound healing and their associated mechanisms, highlighting their novelty and the necessity for further research. This review aims to provide an overview of PELNs, discussing isolation methods, composition, and their mechanisms of action in chronic wound healing. Finally, we summarize future opportunities and challenges related to the use of PELNs for the treatment of chronic wounds, and offer some new insights and solutions.

Quercetin@β-Cyclodextrin Conjugated Keratin/Polyurethane Biocomposite Mats for Infected Diabetic Wound Healing.

Chronic diabetic wounds suffer from severe complications caused by long-term high levels of oxidative stress and bacterial infection. Quercetin (Que) has excellent anti-inflammatory, antioxidant, and antibacterial activity, making it a promising drug to address the above issues. To exploit the benefits of Que in a more effective and sustained way to treat diabetic wounds, carboxymethyl β-cyclodextrin (CMCD) was synthesized and conjugated to keratin, then complexed with Que to form Que@Ker-CMCD inclusion, followed by electrospinning with polyurethane (PU) to afford Que@Ker-CMCD/PU mats. The approach significantly enhanced water solubility, bioavailability, and sustained release of Que. Crucially, these mats exhibited robust antioxidant and antibacterial activities. Moreover, the mats fostered an environment conducive to cell proliferation, migration, angiogenesis, and re-epithelialization, pivotal processes in wound healing and remodeling. Consequently, a marked acceleration in remodeling chronic diabetic wounds was observed. In conclusion, this study introduces a novel therapeutic strategy that not only harnesses the multifaceted benefits of Que but also enhances its delivery and performance, offering a promising avenue for the effective treatment of chronic diabetic wounds.

Emerging Technological Advancement for Chronic Wound Treatment and Their Role in Accelerating Wound Healing.

Chronic wounds are a major healthcare burden and may severely affect the social, mental, and economic status of the patients. Any impairment in wound healing stages due to underlying factors leads to a prolonged healing time and subsequently to chronic wounds. Traditional approaches for the treatment of chronic wounds include dressing free local therapy, dressing therapy, and tissue engineering based scaffold therapies. However, traditional therapies need improvisation and have been advanced through breakthrough technologies. The present review spans traditional therapies and further gives an extensive account of advancements in the treatment of chronic wounds. Cutting edge technologies, such as 3D printing, which includes inkjet printing, fused deposition modeling, digital light processing, extrusion-based printing, microneedle array-based therapies, gene therapy, which includes microRNAs (miRNAs) therapy, and smart wound dressings for real time monitoring of wound conditions through assessment of pH, temperature, oxygen, moisture, metabolites, and their use for planning of better treatment strategies have been discussed in detail. The review further gives the future direction of treatments that will aid in lowering the healthcare burden caused due to chronic wounds.

The versatility of using platelet-enriched autoplasm in medical practice

The search for highly effective and safe methods in regenerative medicine has always been and remains an urgent problem. There are many drugs on the pharmacological market, but they cannot be considered to meet the requirements. One of the potential compounds capable of solving this problem is platelet-enriched autoplasm, which is economical and obtained directly from human blood with further centrifugation and platelet activation. An impressive number of studies are presented in the domestic and foreign literature, which confirm its effectiveness in assessing the area of a wound defect, the rate of regeneration and the absence of side effects. This is ensured by the content of a large number of growth factors and various biologically active compounds. In modern surgical practice, platelet-enriched autoplasm has found extensive use in the treatment of chronic wounds of various etiologies, prone to long-term course and frequent relapses; in cosmetology and aesthetic medicine in the issue of improving the appearance of scars; in urology in the treatment of erectile dysfunction; in obstetric and gynecological practice in improving pregnancy and pregnancy outcomes, reducing recurrence of adhesions, correcting functional sexual dysfunction and a favorable course of in vitro fertilization.

Efficacy and safety of allogeneic platelet-rich plasma in chronic wound treatment: a meta-analysis of randomized controlled trials

Allogeneic platelet-rich plasma (al-PRP) is gaining attention in clinical practice for treating chronic refractory wounds, though research results remain controversial. To assess the clinical efficacy of al-PRP for chronic refractory wounds. Databases including PubMed, Cochrane Library, Embase, CNKI, SinoMed, VIP, and WFPD were searched for randomized controlled trials comparing al-PRP with conventional treatments up to October 2023. Two researchers independently screened studies, extracted data, and assessed quality. Statistical analysis was conducted using RevMan 5.4, and potential publication bias was assessed and corrected using funnel plots and Egger’s test. Twelve studies with 717 cases were included. Meta-analysis showed al-PRP significantly improved outcomes compared to non-al-PRP treatments: increased healing rate (RR 2.72, 95% CI 1.77–4.19, p < 0.00001), shortened healing time (SMD − 1.03, 95% CI -1.31 to -0.75, p < 0.00001), improved efficacy rate (RR 1.19, 95% CI 1.10–1.28, p < 0.00001), increased wound shrinkage (MD 35.65%, 95% CI 21.65–49.64, p < 0.00001), and reduced hospital stays (MD -2.62, 95% CI -4.35 to -0.90, p = 0.003). Al-PRP is a feasible, effective, and safe biological therapy for chronic refractory wounds.Trial registration: PROSPERO Identifier CRD42022374920.

Arginine-Biofunctionalized Ternary Hydrogel Scaffolds of Carboxymethyl Cellulose-Chitosan-Polyvinyl Alcohol to Deliver Cell Therapy for Wound Healing.

Wound healing is important for skin after deep injuries or burns, which can lead to hospitalization, long-term morbidity, and mortality. In this field, tissue-engineered skin substitutes have therapy potential to assist in the treatment of acute and chronic skin wounds, where many requirements are still unmet. Hence, in this study, a novel type of biocompatible ternary polymer hybrid hydrogel scaffold was designed and produced through an entirely eco-friendly aqueous process composed of carboxymethyl cellulose, chitosan, and polyvinyl alcohol and chemically cross-linked by citric acid, forming three-dimensional (3D) matrices, which were biofunctionalized with L-arginine (L-Arg) to enhance cellular adhesion. They were applied as bilayer skin biomimetic substitutes based on human-derived cell cultures of fibroblasts and keratinocytes were seeded and grown into their 3D porous structures, producing cell-based bio-responsive hybrid hydrogel scaffolds to assist the wound healing process. The results demonstrated that hydrophilic hybrid cross-linked networks were formed via esterification reactions with the 3D porous microarchitecture promoted by foam templating and freeze-drying. These hybrids presented chemical stability, physicochemical properties, high moisture adsorption capacity, surface properties, and a highly interconnected 3D porous structure well suited for use as a skin substitute in wound healing. Additionally, the surface biofunctionalization of these 3D hydrogel scaffolds with L-arginine through amide bonds had significantly enhanced cellular attachment and proliferation of fibroblast and keratinocyte cultures. Hence, the in vivo results using Hairless mouse models (an immunocompromised strain) confirmed that these responsive bio-hybrid hydrogel scaffolds possess hemocompatibility, bioadhesion, biocompatibility, adhesiveness, biodegradability, and non-inflammatory behavior and are capable of assisting the skin wound healing process.

The efficacy of hemoglobin spray in wound management: a systematic review and network meta-analysis of comparative studies

Purpose There is no evidence comparing the treatment results of hemoglobin spray and hyperbaric oxygen therapy (HBOT) in chronic wounds. Therefore, we conducted a systematic review and network meta-analysis to explore the efficacy and role of hemoglobin spray in the treatment of chronic wounds. The probabilities of being the best treatment option were estimated and ranked between hemoglobin spray and HBOT. Methods A systematic review and network meta-analysis (NMA) were conducted according to the Preferred Reporting Items for Systematic reviews and Meta-analyses (PRISMA) guidelines and PROSPERO number: CRD42020161396. Results A total of 934 studies were identified from PUBMED and SCOPUS databases, and 112 articles were deleted. Among the 24 studies, 16 RCTs and eight cohort studies met our inclusion criteria. In direct meta-analysis, HBOT had higher proportion of wound healing rate than control with pooled risk ratios (RRs) of 1.67 (95%CI: 1.10, 2.52). Hemoglobin spray had a higher wound healing rate than the control, with a pooled odds ratio (OR) of 1.92 (95%CI: 1.35, 2.73). In the network meta-analysis, the probability of being the best treatment was hemoglobin spray, followed by hyperbaric, with surface under the cumulative ranking curve (SUCRAs) of 67.9, and 32.1, respectively. Conclusions Our evidence suggests that the proportion of wound healing in the hemoglobin spray and HBOT groups was higher than that in the control group. A network meta-analysis demonstrated that hemoglobin spray had the highest chance of treatment success. There is a need for further studies using well-designed RCTs and updated meta-analyses to provide enough evidence to compare the effectiveness of hemoglobin spray and HBOT in clinical practice.

Inflammatory regulation of squid cartilage gelatin with different molecular weights for treatment of chronic wounds in diabetes

Squid, as a very important economic marine species, accounts for 5 % of the total catch of fish and cephalopods. The waste from the processing process of squid can be used for collagen extraction, which has great application value in the field of biomedical materials. Here, we obtained squid cartilage gelatin (SCG) with different molecular weights by adjusti.ng the reaction conditions and used for the treatment of chronic wounds in diabetes. SCG extracted at low temperatures and short heating times demonstrated a more intact structure, higher molecular weight, and superior gel stability. Based on cell study and transcriptome analysis, SCG with high molecular weight significantly promoted cell adhesion, because it provided more contact sites for cells, whereas small molecules of SCG could directly reduce inflammation. Animal studies have demonstrated that SCG significantly promotes diabetic wound healing as evidenced by reducing inflammation, inducing vascular regeneration, promoting tissue growth, re-epithelialization, collagen deposition and remodeling. This study elucidated the immunoregulatory mechanisms of SCG with different molecular weights, and validated its potential application in chronic wound healing in diabetes.