Full-thickness Wound Healing Research Articles

Fabrication and characterization of Rhizochitosan and its incorporation with platelet concentrates to promote wound healing

Composite dressing composed of Rhizochitosan and Regenplex™ to promote wound healing were assessed. Rhizochitosan was fabricated by deacetylation of Rhizochitin, which obtained by simply depigmenting sporangium-free mycelial mattress produced from Rhizopus stolonifer F6. Physicochemical characterizations of Rhizochitosan demonstrated that it contained 13.5% chitosan with a water-absorption ability of 35-fold dry weight and exhibiting hydrogel nature after hydration. In a wound-healing study on SD rats with full-thickness injury, the composite dressing had a better healing effect than those for each individual components and control group and wound even healed as functional tissue instead of scar tissue. The underlying mechanism of the composite beneficial to wound remodeling is likely attributable to a more reduction level of matrix metalloproteinase (MMP)-9 expression in early stage and a higher MMP-2 expression level in a later stage of healing process. Conclusively, the composite dressing demonstrated to be highly beneficial to the healing of full-thickness injury wound.

The role of Helianthus tuberosus powder in healing of full-thickness wounds in mice.

Background and Aim:Recently, many medicinal plants have received considerable attention in the medical field because of their role in the wound healing potential. This study aimed to determine the effectiveness of H. tuberosus powder on the healing pathway of full-thickness cutaneous wounds in a mouse model.Materials and Methods:H. tuberosus powder was prepared by a freeze-drying process using a lyophilizer and its active ingredients were evaluated by high-performance liquid chromatography (HPLC), while its antibacterial properties were evaluated by agar well diffusion assay. The percentage wound contraction was also assessed. Thirty mice were used, which were divided equally into two groups, a control group and a treated group. A full-thickness wound, 1 cm×1 cm in size, was established on the dorsal aspect of the thoracolumbar region, into which H. tuberosus powder was topically applied in the treated group. In contrast, the control group was left without any treatment. The animals were euthanized on days 7, 14, and 21 after wounding for histopathological study.Results:The agar well diffusion method indicated the antibacterial activity of H. tuberosus, while the HPLC results indicated that the active ingredients of H. tuberosus powder mainly consisted of three major kinds of fatty acid. In addition, the macroscopic results of wound contraction rate and the histopathological outcomes of the healing process were significantly (p≤0.05) enhanced in the treated group compared with those in the control group.Conclusion:H. tuberosus powder acts as an antibacterial agent with the ability to enhance the wound healing process.

Evaluation effect of different concentration of povidone Iodine on skin wound healing in rabbits

The goal of the current study was to assess the effects of povidone iodine 10% in comparison with 5% of povidone iodine on full-thickness cutaneous wounds healing in rabbits. This was on twenty-four healthy male rabbits, weighing from (1.5–1.8 kg). Under the effect of intramuscular administration of a mixture of xylazine hydrochloride 5mg / kg, ketamine hydrochloride 35mg / kg and diazepam 1 mg / kg. On each animal, in the dorsal back area, one square (2 × 2) cm full-thickness skin wounds were made. The animals were divided into two groups, group (A) as the treatment group was treated with 10% povidone iodine daily for 1 time for day 7 post operation. While, at the same time in group (B), the rabbits were treated with 5% povidone iodine. For clinical evaluation, each group was divided into four subgroups (two wounds/subgroup) on 3rd, 5th, 7th, 9th, 14th and 21th days post-wound induction and treatment. Clinically, the result showed that 10 % of iodine was more effective than 5 % of iodine, and the wound healing rate in group (A) was faster than group (B). This was followed by statistical analysis results showing the wound healing process ((20%, 40%), (70%, 85%) contraction) and ((10%, 20%), (50%, 70%) re-epithelization). Respectively, there were significantly more (P≤0.05) than the iodine 5% during the study period. Conclusion; Povidone-iodine solution 10% is more efficient than iodine 5% so that lead to acceleration and enhancement of full-thickness cutaneous wounds healing.

Keratin Scaffolds Containing Casomorphin Stimulate Macrophage Infiltration and Accelerate Full-Thickness Cutaneous Wound Healing in Diabetic Mice.

Impaired wound healing is a major medical challenge, especially in diabetics. Over the centuries, the main goal of tissue engineering and regenerative medicine has been to invent biomaterials that accelerate the wound healing process. In this context, keratin-derived biomaterial is a promising candidate due to its biocompatibility and biodegradability. In this study, we evaluated an insoluble fraction of keratin containing casomorphin as a wound dressing in a full-thickness surgical skin wound model in mice (n = 20) with iatrogenically induced diabetes. Casomorphin, an opioid peptide with analgesic properties, was incorporated into keratin and shown to be slowly released from the dressing. An in vitro study showed that keratin-casomorphin dressing is biocompatible, non-toxic, and supports cell growth. In vivo experiments demonstrated that keratin-casomorphin dressing significantly (p < 0.05) accelerates the whole process of skin wound healing to the its final stage. Wounds covered with keratin-casomorphin dressing underwent reepithelization faster, ending up with a thicker epidermis than control wounds, as confirmed by histopathological and immunohistochemical examinations. This investigated dressing stimulated macrophages infiltration, which favors tissue remodeling and regeneration, unlike in the control wounds in which neutrophils predominated. Additionally, in dressed wounds, the number of microhemorrhages was significantly decreased (p < 0.05) as compared with control wounds. The dressing was naturally incorporated into regenerating tissue during the wound healing process. Applied keratin dressing favored reconstruction of more regular skin structure and assured better cosmetic outcome in terms of scar formation and appearance. Our results have shown that insoluble keratin wound dressing containing casomorphin supports skin wound healing in diabetic mice.

Biodegradable multifunctional bioactive Eu-Gd-Si-Ca glass nanoplatform for integrative imaging-targeted tumor therapy-recurrence inhibition-tissue repair

• A multifunctional bioactive tumor imaging-targeted therapy-repair nanoplatform was constructed. • The nanoplatform showed targeted tumor imaging and therapy. • The nanoplatform efficiently inhibited tumor recurrence and enhanced tissue regeneration. The postoperative tissue healing of tumor excision, monitoring of remained tumor cells and inhibiting of tumor recurrence are still the great challenge. Herein, we develop a multifunctional biodegradable silicon-based Eu-Gd-Si-Ca bioactive glass nanoplatform (MBSGN) for tumor imaging, inhibiting tumor recurrence and enhancing tumor-impaired tissue regeneration. MBSGN exhibited a branched mesoporous structure (10–20 nm), controlled biodegradation, ultrahigh drug loading (602.52 mg g −1 ) and pH responsive release behavior, special magneto-optical properties and tumor cell-targeted surface. MBSGN possessed excellent biocompatibility and tumor cell-targeted capacity in vitro . MBSGN showed multi-model bioimaging capacity for skin tumor tissue (fluorescence/magnetic resonance/computed tomography imaging). MBSGN could efficiently eliminate the tumor growth, inhibit the local tumor recurrence through in situ removal of residual tumor cells, greatly enhance the full-thickness wound healing and tumor surgery-caused wounds repair. This study offers a reasonable and promising pathway for in situ integration of multi-modal bio-imaging, recurrent melanoma therapy and tissue regeneration.

The synergistic effect of topical insulin and clindamycin on acute dermal wound healing in rat model: a histological study

ABSTRACT Reducing the duration of wound healing is important to decrease the chance of infection. Insulin as a peptide hormone has a role in wound healing. Also, the use of clindamycin in the treatment of skin wounds has been studied very little. The aim of this study was to evaluate the synergistic effect of insulin and clindamycin on full-thickness wound healing. In this study, 24 Wistar rats (weight 180–200 g) were randomly divided into four equal groups: control (Eucerin), clindamycin, insulin, and insulin + clindamycin. Drugs were administered in the form of an ointment daily for twelve days. Wound healing rate and wound criteria such as epithelialization, neovascularization, collagen deposition, inflammation, and tissue granulation were investigated histologically on days 3, 7, and 14. The wound healing rate in the insulin + clindamycin group was significantly higher than the other groups on day 7 but there was no significant difference between groups on day 14. In addition, the combination of insulin and clindamycin had a beneficial effect on reducing inflammation and increasing collagen deposition, fibroblast maturation, neovascularization, and keratinization. The data showed that the topical application of insulin with clindamycin has an effective role in full-thickness wound healing by reducing inflammation and accelerating wound closure.

Studies of efficacy of Achillea species ethanol extract and honey on full thickness wound healing in diabetic albino rats

Wound healing is deemed a clinical issue in diabetic patients. This study aimed to investigate the efficiency of Achillea species ethanolic extract and honey on wound healing enhancement in streptozotocin-induced diabetic rats. Thirty adult male Albino rats (180- 230 gm) were used for creating full thickness skin wounds. Animals were grouped to control (GI) and diabetics (GII- GVI). Diabetes was induced by streptozotocin (45 mg/kg) and all animals received metformin (50 mg/kg orally for 14 days to control hyperglycemia). Full thickness wound (2X2 cm) was created on the back skin of all animals. Wounded diabetic animals were divided into 5 subgroups based on wound treatment into diabetic wounded untreated (GII), mebo cream (GШ), Achillea extract preparation (GIV), honey (GV), Achillea + honey (GVI). One ml of each treatment was used for daily wound painting by fine brush for 14 days. Wounds were observed daily for healing criteria or complications and photographed with a well-known scale to measure contraction rate. Smears were taken from wounds for microbiological study. Wounded area was dissected at 14 days, processed for paraffin sectioning and staining by hematoxylin and eosin, alpha –smooth actin (α-SA) and proliferating cell nuclear antigen (PCNA). Achillea extract, Achillea + honey, honey and mebo enhanced wound healing in diabetic rats. Most treatments modified microbial contents, blood profile and histological healing process. Achillea extracts, Achillea + honey and honey showed marked influence in enhancing wound healing in diabetic rats even better than mebo. So, it is recommended to use Achillea alone or mixed with honey for enhancing large a wound defects in diabetic patients.

Superabsorbent poly(acrylic acid) and antioxidant poly(ester amide) hybrid hydrogel for enhanced wound healing.

Wound healing dressing is increasingly needed in clinical owing to the large quantity of skin damage annually. Excessive reactive oxygen species (ROS) produced through internal or external environmental influences can lead to lipid peroxidation, protein denaturation, and even DNA damage, and ultimately have harmful effects on cells. Aiming to sufficiently contact with the wound microenvironment and scavenge ROS, superabsorbent poly (acrylic acid) and antioxidant poly (ester amide) (PAA/PEA) hybrid hydrogel has been developed to enhance wound healing. The physical and chemical properties of hybrid hydrogels were studied by Fourier-transform infrared (FTIR) absorption spectrum, compression, swelling, degradation, etc. Besides, the antioxidant properties of hybrid hydrogels can be investigated through the free radical scavenging experiment, and corresponding antioxidant indicators have been tested at the cellular level. Hybrid hydrogel scaffolds supported the proliferation of human umbilical vein endothelial cells and fibroblasts, as well as accelerated angiogenesis and skin regeneration in wounds. The healing properties of wounds in vivo were further assessed on mouse skin wounds. Results showed that PAA/PEA hybrid hydrogel scaffolds significantly accelerated the wound healing process through enhancing granulation formation and re-epithelialization. In summary, these superabsorbent and antioxidative hybrid hydrogels could be served as an excellent wound dressing for full-thickness wound healing.

Gelatin-Modified Cholecyst-Derived Scaffold Promotes Angiogenesis and Faster Healing of Diabetic Wounds.

Compromised angiogenesis is a major factor contributing delayed wound healing in diabetic patients. Graft-assisted healing using synthetic and natural scaffolds supplemented with micromolecules for stimulating angiogenesis is the contemporary tissue engineering strategy for treating diabetic wounds. This study deployed the carbodiimide chemical reaction for coupling gelatin with a porcine cholecyst-derived scaffold (CDS) for enhancing angiogenesis. The modification was confirmed by the trinitrobenzene sulfonic acid assay and scanning electron microscopy. The gelatin-coupled CDS was more stable than the bare CDS in an in vitro proteolytic environment and allowed survival of keratinocytes (HaCaT), indicating its suitability for chronic skin wound application. The gelatin coupling brought significant improvement in the in vitro angiogenic potential of the CDS as evident from the enhanced viability of endothelial cells. An in ovo chorioallantoic membrane assay also demonstrated the angiogenic potential of the modified scaffold. Further, the modified scaffold promoted angiogenesis and aided faster healing of full-thickness excision wounds in streptozotocin-induced diabetic rats. It is concluded that the gelatin-coupled CDS is a potential advanced wound care material for treating diabetic wounds.

A competitive nature-derived multilayered scaffold based on chitosan and alginate, for full-thickness wound healing

The aim of this study was to evaluate a bioactive multilayer wound dressing, based on chitosan and alginate. To enhance healing potential, Dracaena Cinnabari and Aloe Vera were loaded as separate layers into the scaffold. The bare and bioactive multilayered scaffolds were fabricated by an iterative layering freeze-drying technique. Following of topographical, chemical, and physical assessment, the performance of the scaffolds was evaluated in vitro and in vivo. The results revealed adequate attachment, and proliferation of human foreskin fibroblasts, indicating excellent biocompatibility of the bioactive scaffold. In vivo, the performance of the multi-layered scaffold loaded with the bioactive materials was comparable with Comfeel plus®. The wounds treated with the bioactive scaffold exhibited superior hypergranulation, fibroblast maturation, epithelization, and collagen deposition, with minimal inflammation, and crust formation. It is concluded that the synergism of extracellular matrix-mimicking multi-layered scaffolding with Aloe Vera and Dracaena Cinnabari could be considered as a supportive wound dressing.

Mobilization of endothelial progenitor cells promotes angiogenesis after full thickness excision by AMD3100 combined with G-CSF in diabetic mice by SDF-1/CXCR4 axis.

Aim:The aim of the present study was to investigate the effect of the mobilization of EPCs by AMD3100 combined with G-CSF on wound healing in diabetic mice.Methods:The full-thickness excisional wounds model of diabetic mice (db/db) was examined by hematoxylin and eosin staining, immunohistochemical staining, and western blotting to compare the wound healing and neovascularization among the combination, AMD3100 alone, G-CSF alone, and control groups.Results:The wounds reached the complete closure in the combination, AMD3100 alone, G-CSF alone, and control groups on days 17, 20, 21, 21 after surgery, respectively. In addition, the combination group promoted the inflammatory cell recruitment and glandular formation. On day 10 from injury, the protein expression of CD31 in the combination group was significantly higher compared with the other three groups (p < 0.001). The level of SDF-1 protein remained high in the combined group until on day 10 after surgery (p < 0.001).Conclusion:The mobilization of endogenous EPCs by AMD3100 combine with G-CSF is able to enhance the complete healing of full-thickness wounds and neovascularization in db/db mice may by SDF-1/CXCR4 axis. These findings provided a novel method and indication of duration of mobilization on diabetic wound healing and tissue regeneration.

Sprayable antibacterial Persian gum-silver nanoparticle dressing for wound healing acceleration

Wound infection is considered a significant challenge in skin injuries. Sprayable antibacterial wound dressings are interesting alternatives to their traditional counterparts because of their facile preparation, ease-of-use, and the possibility of topical delivery of antibacterial materials. Herein, novel sprayable antibacterial dressings are formulated and reported. The dressings were developed by in-situ formation of Ag-nanoparticles (Ag-NPs) using Persian gum (PG) as a carbohydrate polymer. Several tests were conducted to investigate the effect of polymer concentration on the sprayablity, biocompatibility, and antibacterial activity of the dressings (PG/Ag-NPs). Results showed that formulations up to 2 wt.% PG/Ag-NPs could be sprayed properly and form intact films. Antibacterial evaluations also showed biocidal activity of 1% PG/Ag-NPs against Pseudomonas aeruginosa and Staphylococcus aureus. Cytotoxicity and in vivo full-thickness wound healing evaluation confirmed that 1% PG/Ag-NPs spray was safe and improved wound healing process. All the results confirmed the high potential of formulated sprayable dressings for wound repair.

Recent Advances in the Design of Three-Dimensional and Bioprinted Scaffolds for Full-Thickness Wound Healing.

Three-dimensional (3D) printed scaffolds have recently emerged as an innovative treatment option for patients with critical-sized skin wounds. Current approaches to managing life-threatening wounds include skin grafting and application of commercially sourced skin substitutes. However, these approaches are not without several challenges. Limited donor tissue and donor site morbidity remain a concern for tissue grafting, while engineered skin substitutes fail to fully recapitulate the complex native environment required for wound healing. The implementation of 3D printed dermal scaffolds offers a potential solution for these shortcomings. Spatial control over scaffold structure, the ability to incorporate multiple materials and bioactive ingredients, enables the creation of conditions specifically optimized for wound healing. Three-dimensional bioprinting, a subset of 3D printing, allows for the replacement of lost cell populations and secreted active compounds that contribute to tissue repair and recovery. The replacement of damaged and lost cells delivers beneficial effects directly, or synergistically, supporting injured tissue to recover its native state. Despite encouraging results, the promise of 3D printed scaffolds has yet to be realized. Further improvements to current material formulations and scaffold designs are required to achieve the goal of clinical adoption. Herein, we provide an overview of 3D printing techniques and discuss several strategies for healing of full-thickness wounds by using 3D printed acellular scaffolds or bioprinted cellular scaffolds, aimed at translating this technology to the clinical management of skin lesions. We identify the challenges associated with designing and optimizing printed tissue replacements, and discuss the future perspectives of this emerging option for managing patients who present with critical-sized life-threatening cutaneous wounds. Impact statement Chronic wounds and burn injuries often present with the full-thickness loss of skin, threatening the life of the patient and generating significant socioeconomic burden for these patients, their treating clinicians, and the wider community in which these patients live. Effective clinical management that permits damaged skin tissue to repair and restore its native functional state reduces the strain on health care systems. Three-dimensional (3D) printed scaffolds have been proposed as a potential solution and could be instrumental in facilitating the recovery and healing process. In this review, we will summarize the current research approaches, technologies, and limitations of 3D printed scaffolds as an efficient and effective approach to managing cutaneous wound healing.

Electrospun egg white/polyvinyl alcohol fiber dressing to accelerate wound healing

The purpose of this experiment was to prepare a new biological dressing for skin defect healing by electrospinning. Membranes consisting of egg white (EW) with 12% polyvinyl alcohol (PVA) solution (v/v, 60EW/40PVA, 50EW/50PVA, 40EW/60PVA) were obtained by electrospinning. The biological properties of the resulting fibrous membranes were tested in vitro and in vivo. Scanning electron microscopy (SEM) showed that the EW/PVA nanofiber membranes had a uniformly porous and smooth fibrous structure. The fiber thickened with increasing EW proportion. X-ray diffraction (XRD) showed that crosslinking improved the crystallinity of the composite fiber films. Fourier transform infrared (FT-IR) spectroscopy showed that PVA and EW existed independently in the composite fiber membranes after crosslinking. Mechanical tests showed that the tensile modulus and tensile strength of the fibrous membranes increased significantly after crosslinking. In vitro degradation experiments showed that crosslinking improved the stability of the EW/PVA nanofiber membranes in water. Cytotoxicity and cell proliferation tests proved the good biocompatibility of the fibrous membranes, with 60EW/40PVA significantly promoting cell proliferation. A full-thickness skin defect rat model confirmed that 60EW/40PVA significantly enhanced full-thickness skin wound healing and regeneration. This experiment verified the feasibility of using the EW/PVA composite material to prepare electrospun fiber dressings and promote skin defect repair and regeneration.

Nitric Oxide Produced by the Antioxidant Activity of Verapamil Improves the Acute Wound Healing Process.

Verapamil is used in the treatment of hypertension, angina pectoris, cardiac arrhythmia, hypertrophic scars, and keloids to block transmembrane calcium ion flux. Verapamil has antioxidant activity, which enhances the production of nitric oxide (NO). NO promotes the proliferation of fibroblasts, keratinocytes, endothelial cells, and epithelial cells during wound healing. In this study, we investigated the effect of verapamil and its antioxidant properties on the enhancement of acute wound healing via NO. A full-thickness wound healing model was created on the rat dorsal with a silicone ring. The wound closure rate was estimated every 2days for 14days. A histological study was performed to evaluate wound healing. Immunofluorescence staining was analyzed for angiogenesis. The expressions of collagen type I (COL I), collagen type III (COL III), and vascular endothelial growth factor (VEGF) were assessed by Western blot. Real-time polymerase chain reaction (qRT-PCR) was performed to examine the expression of endothelial NO synthase and inducible NO synthase, which are related to antioxidant activity in the process of wound healing. The wound closure rate was faster in the verapamil group compared to the control and silicone groups. Histologic analysis revealed capillaries and stratum basale in the verapamil group. Immunofluorescence staining was shown vessel formation in the verapamil group. Western blot and qRT-PCR analysis revealed high expression levels of COL I, VEGF, eNOS, and FGF in the verapamil. Verapamil's antioxidant activity enhances NO production in acute wound healing. We suggest that verapamil can be used to promote acute wound healing.

Biomimetic nanoengineered scaffold for enhanced full-thickness cutaneous wound healing

Wound healing is a complex process based on the coordinated signaling molecules and dynamic interactions between the engineered scaffold and newly formed tissue. So far, most of the engineered scaffolds used for the healing of full-thickness skin wounds do not mimic the natural extracellular matrix (ECM) complexity and therefore are not able to provide an appropriate niche for endogenous tissue regeneration [1]. To address this gap and to accelerate the wound healing process, we present biomimetic bilayer scaffolds compositing of gelatin nanofibers (GFS) and photocrosslinkable composite hydrogels loaded with epidermal growth factors (EGF). The nanofibers operate as the dermis layer, and EGF-loaded composite hydrogels acted as the epidermis matrix for the full-thickness wound healing application. The hydrogels are composed of gelatin metacryloyl (GelMA) modified with silicate nanoplatelets (Laponite). To overcome the challenges of transdermal delivery of EGF, including short half-life and lack of efficient formulation precise, controlled delivery was attained by immobilization of EGF on Laponite. It is shown that the addition of 1wt% silicate nanoplatelet increases the compressive modulus of the hydrogels by 170%. In vitro wound closure analysis also demonstrated improved adhesion of the scaffolds to the native tissue by 3.5 folds. Moreover, the tunable hemostatic ability of the scaffolds due to the negatively charged nanoplatelets is shown. In an established excisional full-thickness wound model, an enhanced wound closure (up to 93.1 ± 1.5%) after 14 days relative to controls (GFS and saline-treated groups) is demonstrated. The engineered adhesive and hemostatic scaffolds with sustained release of the growth factors have the potential to stimulate complete skin regeneration for full-thickness wound healing.

Multi-faceted enhancement of full-thickness skin wound healing by treatment with autologous micro skin tissue columns

Impaired wound healing is an immense medical challenge, and while autologous skin grafting remains the “gold-standard” therapeutic option for repairing wounds that cannot be closed by primary or secondary intention, it is limited by substantial donor site morbidity. We previously developed the alternative approach of harvesting full-thickness skin tissue in the form of “micro skin tissue columns” (MSTCs), without causing scarring or any other long-term morbidity. In this study we investigated how MSTC treatment affects the different cellular processes involved in wound healing. We found that MSTC-derived cells were able to remodel and repopulate the wound volume, and positively impact multiple aspects of the wound healing process, including accelerating re-epithelialization by providing multiple cell sources throughout the wound area, increasing collagen deposition, enhancing dermal remodeling, and attenuating the inflammatory response. These effects combined to enhance both epidermal and dermal wound healing. This MSTC treatment approach was designed for practical clinical use, could convey many benefits of autologous skin grafting, and avoids the major drawback of donor site morbidity.

Asiaticoside and polylysine-releasing collagen complex for effectively reducing initial inflammatory response using inflamed induced in vitro model

Inflammation is a significant clinical problem that can arise from full-thickness wounds or burn injuries or microbial disease. Although topical wound healing substances could promote rapid wound healing by preventing or reducing the consequences of inflammation, there still remains a need for the development of novel substances that can effectively reduce infection and inflammation in initial wound healing phase. In this study, collagen was combined with asiaticoside (AS) and ε-poly-l-lysine (εPLL). This complex was then applied to in vitro models of infection and inflammation. Collagen-AS coatings inhibited the initial inflammatory response to LPS through a sustained release of AS, and a bilayer coating-εPLL showed a notable antimicrobial effect using microbial infection test. In this study, we determined whether asiaticoside and εPLL have anti-inflammatory and antibacterial effects through different mechanisms. Collectively, the collagen-AS/εPLL complex indicated great therapeutic potentials for accelerate wound healing and the complex may be considered as a artificial scaffold substitute product to full-thickness wound healing.

Enhanced full-thickness wound healing via Sophora gibbosa extract delivery based on a chitosan/gelatin dressing incorporating microemulsion

There are many synthetic drugs in literature have been utilized in healing of the wounds although the natural product specially antioxidants can offer similar if not better biological activity in that regard. Genus Sophora is well known to contain flavonoids and phenolic compounds which have antioxidant and inflammatory effects. So, the aim of the current study was to develop and evaluate chitosan/gelatin based Sophora gibbosa extract-loaded microemulsion as wound dressing. Sophora gibbosa extract (SGE) contained 16 major compounds which have reasonable antioxidant activity. The developed microemulsion showed that Tween 80 produced significant (p < 0.05) lower particle size than Pluronic F127 at the same SGE concentration whereas high concentration of extract results in large particle size. Thermodynamic stability studies showed that using higher concentration of the extract produced less stable formulations. The selected formulation was impregnated in the dressing base (chitosan/gelatin; 2:1 w/w ratio) which exhibited more water absorption. In vivo evaluation revealed that the dressing displayed superior wound repair compared to the control in terms histological examination and determination of alpha smooth muscle actin (α-SMA) and proliferating cell nuclear antigen (PCNA). Thus, SGE-loaded microemulsion-impregnated gelatin/chitosan could be a potential candidate for the wound healing.

A multifunctional substance P-conjugated chitosan hydrochloride hydrogel accelerates full-thickness wound healing by enhancing synchronized vascularization, extracellular matrix deposition, and nerve regeneration

Due to the native skin limitations and the complexity of reconstructive microsurgery, advanced biomaterials are urgently required to promote wound healing for severe skin defects caused by accidents and disasters. Accumulating evidence has supported that substance P (SP) has a potential effect on skin regeneration. However, SP application is seriously impeded by its poor stability and oxidative reactions occurring during production, transportation, and storage. An SP-conjugated chitosan hydrochloride hydrogel (CSCl-SP) fabricated in this study demonstrated an enhanced capacity to repair full-thickness skin defects. CSCl-SP provided a stable in vitro delivery system for SP. The dissolution of CSCl-SP promoted the proliferation, migration, and tube formation, as well as angiogenesis-related gene and protein expression in human umbilical vein endothelial cells. CSCI-SP also stimulated the proliferation, migration, and production of anabolic growth factor in human fibroblasts. Moreover, CSCl-SP significantly promoted the neurite outgrowth in Neuro-2A cells. In vivo, CSCl-SP dramatically strengthened the vascularization, extracellular matrix deposition and remodeling, and nerve regeneration, thereby promoting efficient recovery of the full-thickness skin defect. Thus, synchronized multifunction of the CSCl-SP hydrogel makes it a promising and smart material for intractable skin defects.