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Fulltext Recent Progress in Development of Dressings Used for Diabetic Wounds with Special Emphasis on Scaffolds

Awasthi A, Gulati M, Kumar B, Kaur J, Vishwas S, Khursheed R, et al.

Biomed Res Int, 2022;2022:1659338.
PMID: 35832856 DOI: 10.1155/2022/1659338

Diabetic wound (DW) is a secondary application of uncontrolled diabetes and affects about 42.2% of diabetics. If the disease is left untreated/uncontrolled, then it may further lead to amputation of organs. In recent years, huge research has been done in the area of wound dressing to have a better maintenance of DW. These include gauze, films, foams or, hydrocolloid-based dressings as well as polysaccharide- and polymer-based dressings. In recent years, scaffolds have played major role as biomaterial for wound dressing due to its tissue regeneration properties as well as fluid absorption capacity. These are three-dimensional polymeric structures formed from polymers that help in tissue rejuvenation. These offer a large surface area to volume ratio to allow cell adhesion and exudate absorbing capacity and antibacterial properties. They also offer a better retention as well as sustained release of drugs that are directly impregnated to the scaffolds or the ones that are loaded in nanocarriers that are impregnated onto scaffolds. The present review comprehensively describes the pathogenesis of DW, various dressings that are used so far for DW, the limitation of currently used wound dressings, role of scaffolds in topical delivery of drugs, materials used for scaffold fabrication, and application of various polymer-based scaffolds for treating DW.

Matched MeSH terms: Wound Healing
Smart and pH-sensitive rGO/Arabinoxylan/chitosan composite for wound dressing: In-vitro drug delivery, antibacterial activity, and biological activities

Khan MUA, Haider S, Raza MA, Shah SA, Razak SIA, Kadir MRA, et al.

Int J Biol Macromol, 2021 Dec 01;192:820-831.
PMID: 34648803 DOI: 10.1016/j.ijbiomac.2021.10.033

Carbohydrate polymers are biological macromolecules that have sparked a lot of interest in wound healing due to their outstanding antibacterial properties and sustained drug release. Arabinoxylan (ARX), Chitosan (CS), and reduced graphene oxide (rGO) sheets were combined and crosslinked using tetraethyl orthosilicate (TEOS) as a crosslinker to fabricate composite hydrogels and assess their potential in wound dressing for skin wound healing. Fourier-transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), atomic force microscopy (AFM), transmission electron microscopy (TEM), and biological assays were used to evaluate the composite hydrogels. FTIR validated the effective fabrication of the composite hydrogels. The rough morphologies of the composite hydrogels were revealed by SEM and AFM (as evident from the Ra values). ATC-4 was discovered to have the roughest surface. TEM revealed strong homogeneous anchoring of the rGO to the polymer matrix. However, with higher amount of rGO agglomeration was detected. The % swelling at various pHs (1-13) revealed that the hydrogels were pH-sensitive. The controlled release profile for the antibacterial drug (Silver sulfadiazine) evaluated at various pH values (4.5, 6.8, and 7.4) in PBS solution and 37 °C using the Franz diffusion method revealed maximal drug release at pH 7.4 and 37 °C. The antibacterial efficacy of the composite hydrogels against pathogens that cause serious skin diseases varied. The MC3T3-E1 cell adhered, proliferated, and differentiated well on the composite hydrogels. MC3T3-E1 cell also illustrated excellent viability (91%) and proper cylindrical morphologies on the composite hydrogels. Hence, the composite hydrogels based on ARX, CS, and rGO are promising biomaterials for treating and caring for skin wounds.

Matched MeSH terms: Wound Healing/drug effects
Topical administration of mangiferin promotes healing of the wound of streptozotocin-nicotinamide-induced type-2 diabetic male rats

Lwin OM, Giribabu N, Kilari EK, Salleh N

J Dermatolog Treat, 2021 Dec;32(8):1039-1048.
PMID: 32013660 DOI: 10.1080/09546634.2020.1721419

PURPOSE: This study identifies the potential use of mangiferin gel to promote wound healing in diabetes mellitus (DM).
MATERIALS AND METHODS: Male rats were rendered diabetes mellitus via intraperitoneal injection of streptozotocin and nicotinamide. Following diabetes development, wound was created at the back of the neck. 1% and 2% mangiferin gel and 1% silver sulphurdiazine (SS) gel (positive control) were applied to the wound for twenty-one (21) days. Fasting blood glucose (FBG) levels were weekly monitored. At the end of the treatment, rats were sacrificed and wound was excised and subjected for histopathological and molecular biological analysis.
RESULTS: No changes to serum FBG levels was noted throughout the period of mangiferin treatment. Albeit, a significant decrease in the size of the wound with increased in the skin thickness of surrounding the wound were observed. Increased expression and distribution of EGF, FGF, TGF-β, VEGF, PI3K, MMP and Nrf2 and decreased expression and distribution of TNFα and NF-κB p65 were observed in diabetic wound treated with topical mangiferin.
CONCLUSIONS: Mangiferin has potential to be used as an agent to promote wound healing in diabetic condition.

Matched MeSH terms: Wound Healing
Maggot debridement therapy to treat hard-to-heal diabetic foot ulcers: a single-centre study

Nair HK, Ahmad NW, Ismail AA, Alabed AAA, Zheming BO, Kaur G, et al.

J Wound Care, 2021 12 01;30(Sup12):S30-S36.
PMID: 34882006 DOI: 10.12968/jowc.2021.30.Sup12.S30

OBJECTIVE: Maggot debridement therapy (MDT) has seen a resurgence in recent years in the treatment of hard-to-heal wounds, as a result of rising antibiotic resistance. The sterilised larvae of Lucilia cuprina have been used in MDT in Malaysia since 2003, with encouraging results for the treatment of hard-to-heal diabetic wounds. We report a case series of 30 patients selected from our clinic by convenient sampling with diabetic lower limb ulcers treated with MDT. The average age of patients receiving MDT was >50 years. Of the 30 patients in the study, nine were female and 21 were male. All patients had underlying diabetes, two patients had leg ulcers and 28 patients had diabetic foot ulcers. Sterilised Lucilia cuprina larvae were applied via a standard method of 10 maggots per square centimetre and dressed with sterile gauze. The study endpoint was defined as ≤5% coverage with slough or necrotic tissue following three successive applications of MDT. In this study, maximum debridement of wounds was achieved in 96.6% (29 patients) of our patients, with ≤5% coverage with slough or necrotic tissue, in addition to a reduction in wound-related pain, as assessed by a visual analogue scale. No adverse events were reported. The findings of this study support the use of MDT as a safe, efficacious, and cost-effective method of managing diabetic wounds.

Matched MeSH terms: Wound Healing
Fulltext Nanotechnology-based therapeutic applications: in vitro and in vivo clinical studies for diabetic wound healing

Haque ST, Saha SK, Haque ME, Biswas N

Biomater Sci, 2021 Nov 23;9(23):7705-7747.
PMID: 34709244 DOI: 10.1039/d1bm01211h

Diabetic wounds often indicate chronic complications that are difficult to treat. Unfortunately, existing conventional treatment modalities often cause unpremeditated side effects, given the need to develop alternative therapeutic phenotypes that are safe or have minimal side effects and risks. Nanotechnology-based platforms, including nanotherapeutics, nanoparticles (NPs), nanofibers, nanohydrogels, and nanoscaffolds, have garnered attention for their groundbreaking potential to decipher the biological environment and offer personalized treatment methods for wound healing. These nanotechnology-based platforms can successfully overcome the impediments posed by drug toxicity, existing treatment modalities, and the physiology and complexity of the wound sites. Furthermore, studies have shown that they play an essential role in influencing angiogenesis, collagen production, and extracellular matrix (ECM) synthesis, which are integral in skin repair mechanisms. In this review, we emphasized the importance of various nanotechnology-based platforms for healing diabetic wounds and report on the innovative preclinical and clinical outcomes of different nanotechnology-based platforms. This review also outlined the limitations of existing conventional treatment modalities and summarized the physiology of acute and chronic diabetic wounds.

Matched MeSH terms: Wound Healing
In vitro methods used for discovering plant derived products as wound healing agents - An update on the cell types and rationale

Low JS, Mak KK, Zhang S, Pichika MR, Marappan P, Mohandas K, et al.

Fitoterapia, 2021 Oct;154:105026.
PMID: 34480992 DOI: 10.1016/j.fitote.2021.105026

Wounds still pose a huge burden on human health and healthcare systems in many parts of the world. Phytomedicines are being used to heal the wounds since ancient times. Now-a-days also many researchers are exploring the wound healing activity of phytomedicines. Wound healing is a complex process thus, it is always a question mark regarding the best test model (in vivo, ex vivo and in vitro) model to assess the wound healing activity of phytomedicines. In general, the researchers would opt for in vivo model - probably because of closer physiological relevance to human wounds. However, in vivo experimental models are not suitable for high throughput screening and not ethical in terms of initial screening of the phytomedicines. The in vivo models are associated with difficulties in obtaining the ethical approvals, requires huge budget, and resources. We argue that judicious selection of cell types would serve the purpose of developing a physiologically relevant in vitro experimental model. A lot of progress has been made in molecular biology techniques to bridge the gap between in vitro models and their physiological relevance. The in vitro models are the best suited for high throughput screening and to elucidate the molecular mechanisms. The main aim of this review is to provide insights on selection of the cell types for developing physiologically relevant in vitro wound healing assays, which can be used to improve the value of phytomedicines further.

Matched MeSH terms: Wound Healing/drug effects*
Fulltext Development of Antibacterial, Degradable and pH-Responsive Chitosan/Guar Gum/Polyvinyl Alcohol Blended Hydrogels for Wound Dressing

Khan MUA, Iqbal I, Ansari MNM, Razak SIA, Raza MA, Sajjad A, et al.

Molecules, 2021 Sep 30;26(19).
PMID: 34641480 DOI: 10.3390/molecules26195937

The present research is based on the fabrication preparation of CS/PVA/GG blended hydrogel with nontoxic tetra orthosilicate (TEOS) for sustained paracetamol release. Different TEOS percentages were used because of their nontoxic behavior to study newly designed hydrogels' crosslinking and physicochemical properties. These hydrogels were characterized using Fourier-transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), and wetting to determine the functional, surface morphology, hydrophilic, or hydrophobic properties. The swelling analysis in different media, degradation in PBS, and drug release kinetics were conducted to observe their response against corresponding media. The FTIR analysis confirmed the components added and crosslinking between them, and surface morphology confirmed different surface and wetting behavior due to different crosslinking. In various solvents, including water, buffer, and electrolyte solutions, the swelling behaviour of hydrogel was investigated and observed that TEOS amount caused less hydrogel swelling. In acidic pH, hydrogels swell the most, while they swell the least at pH 7 or higher. These hydrogels are pH-sensitive and appropriate for controlled drug release. These hydrogels demonstrated that, as the ionic concentration was increased, swelling decreased due to decreased osmotic pressure in various electrolyte solutions. The antimicrobial analysis revealed that these hydrogels are highly antibacterial against Gram-positive (Staphylococcus aureus and Bacillus cereus) and Gram negative (Pseudomonas aeruginosa and Escherichia coli) bacterial strains. The drug release mechanism was 98% in phosphate buffer saline (PBS) media at pH 7.4 in 140 min. To analyze drug release behaviour, the drug release kinetics was assessed against different mathematical models (such as zero and first order, Higuchi, Baker-Lonsdale, Hixson, and Peppas). It was found that hydrogel (CPG2) follows the Peppas model with the highest value of regression (R2 = 0.98509). Hence, from the results, these hydrogels could be a potential biomaterial for wound dressing in biomedical applications.

Matched MeSH terms: Wound Healing/drug effects*
Maggot Debridement Therapy in Malaysia

Nair HKR, Wasi Ahmad N, Teh CH, Lee HL, Chong SSY

Int J Low Extrem Wounds, 2021 Sep;20(3):208-216.
PMID: 32524879 DOI: 10.1177/1534734620932397

Maggot therapy, also known as maggot debridement therapy, larval therapy, biodebridement, or biosurgery, is a type of biotherapy involving the intentional application of live, disinfected fly larvae or maggots into the nonhealing wound of a human or animal to debride the necrotic wound, reduce bacterial contamination of the wound as well as enhance the formation of healthy granulation tissue and stimulate healing in nonhealing wounds. In addition, van der Plas et al reported that the use of the medicinal larvae as natural remover of necrotic and infected tissue had prevented amputation in 11 selected patients. In Malaysia, Aaron et al had demonstrated prevention of amputation in 25 patients.

Matched MeSH terms: Wound Healing*
Cellulose supported magnetic nanohybrids: Synthesis, physicomagnetic properties and biomedical applications-A review

Haniffa MACM, Munawar K, Chee CY, Pramanik S, Halilu A, Illias HA, et al.

Carbohydr Polym, 2021 Sep 01;267:118136.
PMID: 34119125 DOI: 10.1016/j.carbpol.2021.118136

Cellulose and its forms are widely used in biomedical applications due to their biocompatibility, biodegradability and lack of cytotoxicity. It provides ample opportunities for the functionalization of supported magnetic nanohybrids (CSMNs). Because of the abundance of surface hydroxyl groups, they are surface tunable in either homogeneous or heterogeneous solvents and thus act as a substrate or template for the CSMNs' development. The present review emphasizes on the synthesis of various CSMNs, their physicomagnetic properties, and potential applications such as stimuli-responsive drug delivery systems, MRI, enzyme encapsulation, nucleic acid extraction, wound healing and tissue engineering. The impact of CSMNs on cytotoxicity, magnetic hyperthermia, and folate-conjugates is highlighted in particular, based on their structures, cell viability, and stability. Finally, the review also discussed the challenges and prospects of CSMNs' development. This review is expected to provide CSMNs' development roadmap in the context of 21st-century demands for biomedical therapeutics.

Matched MeSH terms: Wound Healing
Curcumin-laden hyaluronic acid-co-Pullulan-based biomaterials as a potential platform to synergistically enhance the diabetic wound repair

Shah SA, Sohail M, Minhas MU, Khan S, Hussain Z, Mahmood A, et al.

Int J Biol Macromol, 2021 Aug 31;185:350-368.
PMID: 34171251 DOI: 10.1016/j.ijbiomac.2021.06.119

Injectable hydrogel with multifunctional tunable properties comprising biocompatibility, anti-oxidative, anti-bacterial, and/or anti-infection are highly preferred to efficiently promote diabetic wound repair and its development remains a challenge. In this study, we report hyaluronic acid and Pullulan-based injectable hydrogel loaded with curcumin that could potentiate reepithelization, increase angiogenesis, and collagen deposition at wound microenvironment to endorse healing cascade compared to other treatment groups. The physical interaction and self-assembly of hyaluronic acid-Pullulan-grafted-pluronic F127 injectable hydrogel were confirmed using nuclear magnetic resonance (1H NMR) and Fourier transformed infrared spectroscopy (FT-IR), and cytocompatibility was confirmed by fibroblast viability assay. The CUR-laden hyaluronic acid-Pullulan-g-F127 injectable hydrogel promptly undergoes a sol-gel transition and has proved to potentiate wound healing in a streptozotocin-induced diabetic rat model by promoting 93% of wound closure compared to other groups having 35%, 38%, and 62%. The comparative in vivo study and histological examination was conducted which demonstrated an expeditious recovery rate by significantly reducing the wound healing days i.e. 35 days in a control group, 33 days in the CUR suspension group, 21 days in unloaded injectable, and 13 days was observed in CUR loaded hydrogel group. Furthermore, we suggest that the injectable hydrogel laden with CUR showed a prompt wound healing potential by increasing the cell proliferation and serves as a drug delivery platform for sustained and targeted delivery of hydrophobic moieties.

Matched MeSH terms: Wound Healing/drug effects*
Restitution of epithelial cells during intestinal mucosal wound healing: The effect of a polysaccharide from the sclerotium of Lignosus rhinocerotis (Cooke) Ryvarden

Veeraperumal S, Qiu HM, Tan CS, Ng ST, Zhang W, Tang S, et al.

J Ethnopharmacol, 2021 Jun 28;274:114024.
PMID: 33727110 DOI: 10.1016/j.jep.2021.114024

ETHNOPHARMACOLOGICAL RELEVANCE: Lignosus rhinocerotis (Cooke) Ryvarden cultivar TM02, also known as tiger's milk mushroom, is regarded as important folk medicine in Malaysia, while is used for the treatment of liver cancer, chronic hepatitis, gastric ulcer in traditional Chinese medicine. However, there is no compilation of scientific evidence that its protection for gastric, and no attempts have been made to understand how polysaccharides in Lignosus rhinocerotis might promote intestinal mucosal wound healing.
AIM OF THE STUDY: This study aimed to investigate the effect and mechanism of β-glucan prepared from L. rhinocerotis using an enzymatic method on epithelial restitution during intestinal mucosal damage.
MATERIALS AND METHODS: Based on FT-IR, MALDI-TOF-MS, HPSEC-MALLS-RID, and AFM, the structure of polysaccharides from L. rhinocerotis was analysed. In addition, polysaccharides were used to test for wound healing activity in IEC-6 cells by measuring cell migration, proliferation, and expression of cell division control protein 42, Rac-1, RhoA, and Par-3.
RESULTS: β-glucan was extracted using enzyme-assisted extraction, and a yield of approximately 8.5 ± 0.8% was obtained from the dried biomass. The β-glucan extracted by enzyme-assisted extraction (EAE) of polysaccharides was composed entirely of D-glucose with a total carbohydrate content of 95.5 ± 3.2%. The results of HPLC, FTIR, and MALDI-TOF-MS analyses revealed EAEP to be confirmed as β-glucan. The molecular weight of prepared β-glucan was found to be 5.315 × 104 g/mol by HPSEC-MALLS-RID. Furthermore, mucosal wound healing studies showed that the treatment of IEC-6 with a β-glucan concentration of 200 μg/mL promoted cell migration and proliferation, and it enhanced the protein expression of cell division control protein 42, Rac-1, RhoA, and Par-3.
CONCLUSIONS: The present study reveals that the prepared β-glucan accelerates intestinal epithelial cell proliferation and migration via activation of Rho-dependent pathway. Hence, β-glucan can be employed as a prospective therapeutic agent for the treatment of diseases associated with gastrointestinal mucosal damage, such as peptic ulcers and inflammatory bowel disease.

Matched MeSH terms: Wound Healing/drug effects*
Fulltext The Role of Calcium in Wound Healing

Subramaniam T, Fauzi MB, Lokanathan Y, Law JX

Int J Mol Sci, 2021 Jun 17;22(12).
PMID: 34204292 DOI: 10.3390/ijms22126486

Skin injury is quite common, and the wound healing is a complex process involving many types of cells, the extracellular matrix, and soluble mediators. Cell differentiation, migration, and proliferation are essential in restoring the integrity of the injured tissue. Despite the advances in science and technology, we have yet to find the ideal dressing that can support the healing of cutaneous wounds effectively, particularly for difficult-to-heal chronic wounds such as diabetic foot ulcers, bed sores, and venous ulcers. Hence, there is a need to identify and incorporate new ideas and methods to design a more effective dressing that not only can expedite wound healing but also can reduce scarring. Calcium has been identified to influence the wound healing process. This review explores the functions and roles of calcium in skin regeneration and reconstruction during would healing. Furthermore, this review also investigates the possibility of incorporating calcium into scaffolds and examines how it modulates cutaneous wound healing. In summary, the preliminary findings are promising. However, some challenges remain to be addressed before calcium can be used for cutaneous wound healing in clinical settings.

Matched MeSH terms: Wound Healing/drug effects; Wound Healing/physiology*
Gelatin Hydrogels Loaded with Lactoferrin-Functionalized Bio-Nanosilver as a Potential Antibacterial and Anti-Biofilm Dressing for Infected Wounds: Synthesis, Characterization, and Deciphering of Cytotoxicity

Suleman Ismail Abdalla S, Katas H, Chan JY, Ganasan P, Azmi F, Fauzi MB

Mol Pharm, 2021 05 03;18(5):1956-1969.
PMID: 33822631 DOI: 10.1021/acs.molpharmaceut.0c01033

Gelatin hydrogels are attractive for wound applications owing to their well-defined structural, physical, and chemical properties as well as good cell adhesion and biocompatibility. This study aimed to develop gelatin hydrogels incorporated with bio-nanosilver functionalized with lactoferrin (Ag-LTF) as a dual-antimicrobial action dressing, to be used in treating infected wounds. The hydrogels were cross-linked using genipin prior to loading with Ag-LTF and characterized for their physical and swelling properties, rheology, polymer and actives interactions, and in vitro release of the actives. The hydrogel's anti-biofilm and antibacterial performances against S. aureus and P. aeruginosa as well as their cytotoxicity effects were assessed in vitro, including primary wound healing gene expression of human dermal fibroblasts (HDFs). The formulated hydrogels showed adequate release of AgNPs and LTF, with promising antimicrobial effects against both bacterial strains. The Ag-LTF-loaded hydrogel did not significantly interfere with the normal cellular functions as no alteration was detected for cell viability, migration rate, and expression of the target genes, suggesting the nontoxicity of Ag-LTF as well as the hydrogels. In conclusion, Ag-LTF-loaded genipin-cross-linked gelatin hydrogel was successfully synthesized as a new approach for fighting biofilms in infected wounds, which may be applied to accelerate healing of chronic wounds.

Matched MeSH terms: Wound Healing/drug effects
Fulltext Dielectrophoresis Prototypic Polystyrene Particle Synchronization toward Alive Keratinocyte Cells for Rapid Chronic Wound Healing

Deivasigamani R, Maidin NNM, Wee MFMR, Mohamed MA, Buyong MR

Sensors (Basel), 2021 Apr 25;21(9).
PMID: 33922993 DOI: 10.3390/s21093007

Diabetes patients are at risk of having chronic wounds, which would take months to years to resolve naturally. Chronic wounds can be countered using the electrical stimulation technique (EST) by dielectrophoresis (DEP), which is label-free, highly sensitive, and selective for particle trajectory. In this study, we focus on the validation of polystyrene particles of 3.2 and 4.8 μm to predict the behavior of keratinocytes to estimate their crossover frequency (fXO) using the DEP force (FDEP) for particle manipulation. MyDEP is a piece of java-based stand-alone software used to consider the dielectric particle response to AC electric fields and analyzes the electrical properties of biological cells. The prototypic 3.2 and 4.8 μm polystyrene particles have fXO values from MyDEP of 425.02 and 275.37 kHz, respectively. Fibroblast cells were also subjected to numerical analysis because the interaction of keratinocytes and fibroblast cells is essential for wound healing. Consequently, the predicted fXO from the MyDEP plot for keratinocyte and fibroblast cells are 510.53 and 28.10 MHz, respectively. The finite element method (FEM) is utilized to compute the electric field intensity and particle trajectory based on DEP and drag forces. Moreover, the particle trajectories are quantified in a high and low conductive medium. To justify the simulation, further DEP experiments are carried out by applying a non-uniform electric field to a mixture of different sizes of polystyrene particles and keratinocyte cells, and these results are well agreed. The alive keratinocyte cells exhibit NDEP force in a highly conductive medium from 100 kHz to 25 MHz. 2D/3D motion analysis software (DIPP-MotionV) can also perform image analysis of keratinocyte cells and evaluate the average speed, acceleration, and trajectory position. The resultant NDEP force can align the keratinocyte cells in the wound site upon suitable applied frequency. Thus, MyDEP estimates the Clausius-Mossotti factors (CMF), FEM computes the cell trajectory, and the experimental results of prototypic polystyrene particles are well correlated and provide an optimistic response towards keratinocyte cells for rapid wound healing applications.

Matched MeSH terms: Wound Healing
Accelerated wound closure - Systematic evaluation of cellulose acetate effects on biologically active molecules release from amniotic fluid stem cells (AFSCs)

Nuge T, Liu X, Tshai KY, Lim SS, Nordin N, Hoque ME, et al.

Biotechnol Appl Biochem, 2021 Apr 07.
PMID: 33826152 DOI: 10.1002/bab.2162

Despite a lot of intensive research on cells-scaffolds interaction, focused are mainly on the capacity of construct scaffolds to regulate cell mobility, migration and cytotoxicity. The effect of the scaffold's topographical and material properties on the expression of biologically active compounds from stem cells is not well understood. In this study, the influence of cellulose acetate (CA) on the electrospinnability of gelatin and the roles of gelatin-cellulose acetate (Ge-CA) on modulating the release of biologically active compounds from amniotic fluid stem cells (AFSCs) is emphasized. It was found that the presence of a small amount of CA could provide a better microenvironment that mimics AFSCs' niche. However, a large amount of CA exhibited no significant effect on AFSCs migration and infiltration. Further study on the effect of surface topography and mechanical properties on AFSCs showed that the tailored microenvironment provided by the Ge-CA scaffolds had transduced physical cues to biomolecules released into the culture media. It was found that the AFSCs seeded on electrospun scaffolds with less CA proportions has profound effects on the secretion of metabolic compounds compared to those with higher CA contained and gelatin coating. The enhanced secretion of biologically active molecules by the AFSCs on the electrospun scaffolds was proven by the accelerated wound closure on the injured human dermal fibroblast (HDF) model. The rapid HDF cell migration could be anticipated due to a higher level of paracrine factors in AFSCs media. Our study demonstrates that the fibrous topography and mechanical properties of the scaffold is a key material property that modulates the high expression of biologically active compounds from the AFSCs. The discovery elucidates a new aspect of material functions and scaffolds material-AFSCs interaction for regulating biomolecules release to promote tissue regeneration/repair. To the best of our knowledge, this is the first report describing the scaffolds material-AFSCs interaction and the efficacy of scratch assays on quantifying the cell migration in response to the AFSCs metabolic products. This article is protected by copyright. All rights reserved.

Matched MeSH terms: Wound Healing
Benefits of sucrose octasulfate (TLC-NOSF) dressings in the treatment of chronic wounds: a systematic review

Nair H, Venkateshwaran N, Seetharaman S S, Deng W, Uthaipaisanwong A, Galea E

J Wound Care, 2021 Apr 01;30(Sup4):S42-S52.
PMID: 33856929 DOI: 10.12968/jowc.2021.30.Sup4.S42

OBJECTIVE: Management of chronic wounds remains one of the major challenges for health professionals and patients. An evidence-based decision is important to ensure that patients are receiving the best treatment proven to reduce healing time and improve outcomes, including economic benefits and patients' health-related quality of life (HRQoL). Due to recent restrictions because of the COVID-19 pandemic, including closure of wound care centres within hospitals and a drop in patient volume, chronic wound management needs simple-to-use dressings which are still effective and evidence-based solutions. This systematic review was conducted to identify the clinical evidence available on a sucrose octasulfate dressing (TLC-NOSF, UrgoStart dressing range, Laboratoires Urgo, France) to explore its efficacy in the management of chronic wounds, particularly lower limb ulcers, diabetic foot ulcers and pressure ulcers.
METHOD: A literature search of PubMed, Cochrane Library and Google Scholar was conducted based on the PICO model (patient/population, intervention, comparison and outcomes) to retrieve publications of different levels of evidence in order to evaluate outcomes of the use of TLC-NOSF dressings.
RESULTS: A total of 21 publications of different levels, ranging from double-blind randomised control trials to case reports, involving over 12,000 patients, were identified through PubMed, with a further eight publications through Google Scholar and two publications through Cochrane Library. A total of seven results were omitted due to the lack of relevance or repetition.
CONCLUSION: All the evidence provided suggest that these dressings provide clinicians with an evidence-based option for the management of chronic wounds; that the TLC-NOSF dressings are beneficial in promoting the healing process, reducing healing times, enhancing patients' HRQoL, and in allowing a more cost-effective procedure.

Matched MeSH terms: Wound Healing/physiology*
Fulltext Beneficial Role of Carica papaya Extracts and Phytochemicals on Oxidative Stress and Related Diseases: A Mini Review

Kong YR, Jong YX, Balakrishnan M, Bok ZK, Weng JKK, Tay KC, et al.

Biology (Basel), 2021 Apr 01;10(4).
PMID: 33916114 DOI: 10.3390/biology10040287

Oxidative stress is a result of disruption in the balance between antioxidants and pro-oxidants in which subsequently impacting on redox signaling, causing cell and tissue damages. It leads to a range of medical conditions including inflammation, skin aging, impaired wound healing, chronic diseases and cancers but these conditions can be managed properly with the aid of antioxidants. This review features various studies to provide an overview on how Carica papaya help counteract oxidative stress via various mechanisms of action closely related to its antioxidant properties and eventually improving the management of various oxidative stress-related health conditions. Carica papaya is a topical plant species discovered to contain high amounts of natural antioxidants that can usually be found in their leaves, fruits and seeds. It contains various chemical compounds demonstrate significant antioxidant properties including caffeic acid, myricetin, rutin, quercetin, α-tocopherol, papain, benzyl isothiocyanate (BiTC), and kaempferol. Therefore, it can counteract pro-oxidants via a number of signaling pathways that either promote the expression of antioxidant enzymes or reduce ROS production. These signaling pathways activate the antioxidant defense mechanisms that protect the body against both intrinsic and extrinsic oxidative stress. To conclude, Carica papaya can be incorporated into medications or supplements to help manage the health conditions driven by oxidative stress and further studies are needed to investigate the potential of its chemical components to manage various chronic diseases.

Matched MeSH terms: Wound Healing
Fulltext Pharmaco-Technical Evaluation of Statistically Formulated and Optimized Dual Drug-Loaded Silica Nanoparticles for Improved Antifungal Efficacy and Wound Healing

Masood A, Maheen S, Khan HU, Shafqat SS, Irshad M, Aslam I, et al.

ACS Omega, 2021 Mar 30;6(12):8210-8225.
PMID: 33817480 DOI: 10.1021/acsomega.0c06242

The current research aimed at designing mesoporous silica nanoparticles (MSNs) for a controlled coadministration of salicylic acid (SA) and ketoconazole (KCZ) to effectively treat highly resistant fungal infections. The sol-gel method was used to formulate MSNs, which were further optimized using central composite rotatable design (CCRD) by investigating mathematical impact of independent formulation variables such as pH, stirring time, and stirring speed on dependent variables entrapment efficiency (EE) and drug release. The selected optimized MSNs and pure drugs were subjected to comparative in vitro/in vivo antifungal studies, skin irritation, cytotoxicity, and histopathological evaluations. The obtained negatively charged (-23.1), free flowing spherical, highly porous structured MSNs having a size distribution of 300-500 nm were suggestive of high storage stability and improved cell proliferation due to enhanced oxygen supply to cells. The physico-chemical evaluation of SA/KCZ-loaded MSNs performed through powder X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FT-IR), and thermal gravimetric analysis (TGA) indicates absolute lack of any interaction between formulation components and successful encapsulation of both drugs in MSNs. The EESA, EEKCZ, SA release, and KCZ release varied significantly from 34 to 89%, 36 to 85%, 39 to 88%, and 43 to 90%, respectively, indicating the quadratic impact of formulation variables on obtained MSNs. For MSNs, the skin tolerability and cell viability percentage rate were also having an extraordinary advantage over suspension of pure drugs. The optimized SA/KCZ-loaded MSNs demonstrated comparatively enhanced in vitro/in vivo antifungal activities and rapid wound healing efficacy in histopathological evaluation without any skin irritation impact, suggesting the MSNs potential for the simultaneous codelivery of antifungal and keratolyic agents in sustained release fashion.

Matched MeSH terms: Wound Healing
Fulltext Epidermal and fibroblast growth factors incorporated polyvinyl alcohol electrospun nanofibers as biological dressing scaffold

Asiri A, Saidin S, Sani MH, Al-Ashwal RH

Sci Rep, 2021 Mar 11;11(1):5634.
PMID: 33707606 DOI: 10.1038/s41598-021-85149-x

In this study, single, mix, multilayer Polyvinyl alcohol (PVA) electrospun nanofibers with epidermal growth factor (EGF) and fibroblast growth factor (FGF) were fabricated and characterized as a biological wound dressing scaffolds. The biological activities of the synthesized scaffolds have been verified by in vitro and in vivo studies. The chemical composition finding showed that the identified functional units within the produced nanofibers (O-H and N-H bonds) are attributed to both growth factors (GFs) in the PVA nanofiber membranes. Electrospun nanofibers' morphological features showed long protrusion and smooth morphology without beads and sprayed with an average range of 198-286 nm fiber diameter. The fiber diameters decrement and the improvement in wettability and surface roughness were recorded after GFs incorporated within the PVA Nanofibers, which indicated potential good adoption as biological dressing scaffolds due to the identified mechanical properties (Young's modulus) in between 18 and 20 MPa. The MTT assay indicated that the growth factor release from the PVA nanofibers has stimulated cell proliferation and promoted cell viability. In the cell attachment study, the GFs incorporated PVA nanofibers stimulated cell proliferation and adhered better than the PVA control sample and presented no cytotoxic effect. The in vivo studies showed that compared to the control and single PVA-GFs nanofiber, the mix and multilayer scaffolds gave a much more wound reduction at day 7 with better wound repair at day 14-21, which indicated to enhancing tissue regeneration, thus, could be a projected as a suitable burn wound dressing scaffold.

Matched MeSH terms: Wound Healing/drug effects
Fulltext Evaluation of Functional Outcome Following Hybrid External Fixation in The Management of Schatzkers Type V and VI Tibial Plateau Fractures - A Prospective Study of 30 Patients

Subash Y

Malays Orthop J, 2021 Mar;15(1):48-54.
PMID: 33880148 DOI: 10.5704/MOJ.2103.008

Introduction: Fractures of the proximal tibia are high velocity injuries often associated with soft tissue compromise especially in the type V and VI fracture patterns. Dual plating is the preferred treatment option for these injuries but not in a setting where there is extensive soft tissue injury, as this can lead to problems with wound healing. The aim of this study was to evaluate the functional outcome following hybrid external fixation in the management of Schatzkers type V and VI fractures.
Materials and Methods: A total of 30 patients with type V and VI proximal tibial fractures who presented between January 2012 to January 2015 were managed with hybrid external fixation and were followed-up for a period of 3 years.
Results: The mean age of the patients was 42.26 years with the left knee being more commonly affected. Schatzkers type V was the more common fracture type seen. The mean time to union was 12.06 weeks and the average range of motion achieved was 0 to 100°. The mean Rasmussens functional score was 25.4 at last follow-up and we had excellent results in 5 patients and good results in 22 patients.
Conclusion: Through this study, we conclude that the hybrid external fixation is an excellent option in the type V and VI fractures with extensive soft tissue compromise. It is easy to apply, facilitates early mobilisation of the joint and gives good functional results.

Matched MeSH terms: Wound Healing

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