Injectable hydrogel wound dressing based on strontium ion cross-linked starch

Severe skin wounds cause great problems and sufferings to patients. In this study, an injectable wound dressing based on strontium ion cross-linked starch hydrogel (SSH) was developed and evaluated. The good inject-ability of SSH made it easy to be delivered onto the wound surface. The good tissue adhesiveness of SSH ensured a firm protection of the wound. Besides, SSH supported the proliferation of NIH/3T3 fibroblasts and facilitated the migration of human umbilical vein endothelial cells (HUVECs). Importantly, SSH exhibited strong antibacterial effects on Staphylococcus aureus (S. aureus), which could prevent wound infection. These results demonstrate that SSH is a promising wound dressing material for promoting wound healing.     

A Self‐Pumping Dressing for Draining Excessive Biofluid around Wounds

Excessive biofluid around wounds often causes infection and hinders wound healing. However, the intrinsic hydrophilicity of the conventional dressing inevitably retains excessive biofluid at the interface between the dressing and the wound. Herein, a self‐pumping dressing is reported, by electrospinning a hydrophobic nanofiber array onto a hydrophilic microfiber network, which can unidirectionally drain excessive biofluid away from wounds and finally accelerate the wound healing process. The hydrophilic microfiber network offers a draining force to pump excessive biofluid through the hydrophobic nanofiber array, which can further keep those pumped biofluids from rewetting the wounds. In the proof of concept, the self‐pumping dressing unidirectionally drains the biofluid from murine dorsum wounds, thereby resulting in faster wound healing than conventional dressings. This unique self‐pumping dressing has enormous potential to be a next‐generation dressing for healing wounds clinically.     

Development of fibroblast culture in three-dimensional activated carbon fiber-based scaffold for wound healing

This work developed a novel bi-layer wound dressing composed of 3D activated carbon fibers that allows facilitates fibroblast cell growth and migration to a wound site for tissue reconstruction, and the gentamicin is incorporated into a poly(γ-glutamic acid)/gelatin membrane to prevent bacterial infection. In an in vitro, field emission scanning electron microscopy shows that rat skin fibroblasts appeared and spread on the surface of activated carbon fibers, and penetrated the interior and exterior of the 3D activated carbon fiber construct to a depth of roughly 200 μm. An in vivo analysis shows that fibroblast cells containing the proposed 3D scaffold had the potential of a biologically functionalized dressing to accelerate wound closure. Additionally, fibroblasts migrated to the wound site in a bi-layer wound dressing containing fibroblasts, enhancing fibronectin and type I collagen expression, resulting in faster skin regeneration than that achieved with a Tegaderm? hydrocolloid dressing or gauze.     

In vivo tests of a novel wound dressing based on biomaterials with tissue adhesion controlled through external stimuli

The high incidence of wounds by second intention and the high costs associated with their treatment give rise to the need for the development of wound dressings that protect not only the wounds themselves but that are also able to promote cell proliferation and skin regeneration. Moreover, it is also very important that no damage to the new regenerated tissue is generated while removing the dressing. In this work, a novel wound dressing, which would be able to favor tissue repair and be removed at an appropriate scheduled moment by means of an external stimulus without promoting extensive damage to the new tissue, was produced and tested. Polyurethane membranes were modified by grafting polymers based on poly(n-isopropylacrylamide) (P-N-IPAAm). P-N-IPAAm undergoes a phase transition at approximately 32°C, which changes its behavior from hydrophilic (below 32°C) to hydrophobic. It was hypothesized that, by reducing the temperature near the wound dressing to values lower than 32°C, the detachment of the dressing would become more effective. The wound dressings containing P-N-IPAAm grafts were tested in vivo by covering excisional wounds produced in mice. The produced dressings were placed in direct contact with the lesions for 3 days. Results showed that the hypothermia due to anesthesia required to remove the dressings from mice lowered the local temperature to 28°C and favored the detachment of the wound dressings containing P-N-IPAAm grafts. Histological analyses showed that lesions covered by dressings presented less intense inflammatory events and denser connective tissue than did the wounds without dressings. The wounds covered by polyurethane membranes with P-N-IPAAm grafts showed signs of more intense re-epithelization and angiogenesis than did the lesions covered by polyurethane without grafts.     

Similarities and differences between induced organ regeneration in adults and early foetal regeneration.

At least three organs (skin, peripheral nerves and the conjunctiva) have been induced to regenerate partially in adults following application of porous, degradable scaffolds with highly specific structure (templates). Templates blocked contraction and scar formation by inducing a reduction in the density of contractile fibroblasts (probably myofibroblasts) and by preventing these cells to organize themselves appropriately in the wound. In contrast, during early foetal healing, myofibroblasts were absent and wounds did not close by contraction but rather by spontaneous regeneration. The adult regenerative process has so far led to imperfect recovery of the physiological anatomy of skin (skin appendages were missing), while early foetal healing has led to apparently complete restoration. Furthermore, the mechanism of the adult regenerative process involves thwarting of myofibroblast function while, during early foetal healing, differentiation of myofibroblasts has not yet occurred. The data suggest that induced organ regeneration in the adult is the result of partial reversion to early foetal healing. If so, the adult may conceal a foetal response that may be subject to activation following application of highly active scaffolds or of other substances or cells.     

Small extracellular vesicles secreted by urine-derived stem cells enhanced wound healing in aged mice by ameliorating cellular senescence

Regeneration of chronic skin wounds in tissue is still a key challenge in regenerative medicine because of the accumulation of senescent cells and increasing secretion of s¨enescence-associated secretory phenotype(SASP)in the wound site.Recently,some studies have reported that small extracellular vesicles(sEVs)derived from stem cells can alleviate cellular senescence with very low risk of tumorigenesis and immune responses.As our previous studies have shown that urine-derived stem cells(USCs)can be obtained easily and noninvasively and sEVs derived from USCs(USC-sEVs)have capabilities of regenerating tissue injuries,using USC-sEVs to enhance chronic skin wound healing in aged tissue might be a feasible and efficient strategy.Therefore,in this study,the USC-sEVs were collected and firstly loaded in a human acellular amniotic membrane(HAAM)for controlled releasing and locating the USC-sEVs in the wound site before they were implanted into a chronic skin wound in aged mice.In vivo results showed that the USC-sEVs in HAAM could effectively accelerate the wound healing by ameliorating cellular senescence and reducing the secretion of SASP in the aged skin wounds.To elucidate the mechanism,USC-sEVs were used to in vitro culture human dermal fibroblasts(HDFs)and results showed that USC-sEVs could rejuvenate senescent fibroblasts by reversing the aging phenotypes of senescent HDFs and efficiently reducing the secretion of SASP after they activated the Sirt1 pathway.Therefore,USC-sEVs are efficient for enhancing wound healing in aged mice by ameliorating cellular senescence.     

In vitro and in vivo evaluations of phenytoin sodium-loaded electrospun PVA, PCL, and their hybrid nanofibrous mats for use as active wound dressings

In this work, polyvinyl alcohol (PVA), poly(ε-caprolactone) (PCL), and their electrospun PVA/PCL (80/20) hybrid nanofibrous mats were used for the development of active wound dressings. The biocompatibility and therapeutic effects of the developed products were studied by in vitro cell culture and in vivo experimental rat wound model. The release rate measurements by HPLC showed that the PVA nanofibrous sample containing phenytoin sodium (PHT-Na) has a higher level of the drug release compared to the hybrid PVA/PCL (80/20) and PCL nanofibrous mats. A mesenchymal stem cell was seeded on neat as well as drug-loaded PVA nanofibrous mats. The results represented that the mats provide a suitable environment for cell growth and viability. PVA nanofibers containing PHT-Na have a unique performance for fibroblasts and myofibroblasts cells formation and consequently reaching to the remodeling phase and faster healing of the wounds. Also, PHT-Na-loaded electrospun PVA nanofibrous mats showed a remarkable efficiency in wound closure compared with the treatments results from gauze, commercial wound dressing Comfeel^®Plus, and 2 % PHT-Na ointment. Histology analysis showed the formation of epidermis, the lack of necrosis, and accumulation of collagen fibers in dermis for PVA nanofibrous mats containing PHT-Na.     

Microalgae-Based Biohybrid Microrobot for Accelerated Diabetic Wound Healing

A variety of wound healing platforms have been proposed to alleviate the hypoxic condition and/or to modulate the immune responses for the treatment of chronic wounds in diabetes. However, these platforms with the passive diffusion of therapeutic agents through the blood clot result in the relatively low delivery efficiency into the deep wound site. Here, a microalgae-based biohybrid microrobot for accelerated diabetic wound healing is developed. The biohybrid microrobot autonomously moves at velocity of 33.3 µm s⁻¹ and generates oxygen for the alleviation of hypoxic condition. In addition, the microrobot efficiently bound with inflammatory chemokines of interleukin-8 (IL-8) and monocyte chemoattractant protein-1 (MCP-1) for modulating the immune responses. The enhanced penetration of microrobot is corroborated by measuring fibrin clots in biomimetic wound using microfluidic devices and the enhanced retention of microrobot is confirmed in the real wounded mouse skin tissue. After deposition on the chronic wound in diabetic mice without wound dressing, the wounds treated with microrobots are completely healed after 9 days with the significant decrease of inflammatory cytokines below 31% of the control level and the upregulated angiogenesis above 20 times of CD31⁺ cells. These results confirm the feasibility of microrobots as a next-generation platform for diabetic wound healing.     

Fabrication and evaluation of polyurethane-based asymmetric membranes

For preparation of an ideal wound dressing, a series of novel polyurethane-based asymmetric membranes with acetic starch and poly (ethylene glycol) as fillers were successfully fabricated by a combination of polymer-filler hybridization and immersion precipitation phase inversion. These resultant polyurethane-based asymmetric membranes consisted of an integral and dense skin layer supported by a porous sublayer as designed. The porosity and internal substructure of asymmetric membranes could be controlled by adjusting species and amount of fillers. The polyurethane-based asymmetric membranes showed promoted fluid absorption capability and controlled water vapor transmission, but could inhibit exogenous microorganisms invasion deriving from its dense skin layer. In vitro biodegradation assay indicated that the polyurethane/acetic starch composite membrane exhibited faster degradation behavior. These results indicated that the polyurethane-based asymmetric membranes prepared in this study has potential for application as an ideal wound dressing.     

Preparation of green cellulose diacetate-based antibacterial wound dressings for wound healing

Managing wounds is a growing universal problem and developing effective wound dressings to staunch bleeding and protect wounds from bacterial infections is an increasingly serious challenge. In this work, a remolding electrospinning nanofiber three-dimensional structure wound dressing (CCP) was prepared with superhydrophilicity, high water absorption and absorbing capacity, excellent hemostatic capacity and antibacterial ability, and biocompatibility to promote wound healing. Polyhexamethylene guanidine hydrochloride (PHMG) was grafted to cellulose diacetate (CDA) wound dressing surface through an amide reaction. A water contact angle analysis demonstrated that CCP wound dressing could be beneficial to promote wound exudate management effectively with rapid absorption of water within 0.2 s. In vitro hemo- and cytocompatibility assay showed that a CCP wound dressing had no significant hemotoxicity or cytoxicity. Specifically, CCP wound dressings could be beneficial to accelerate wound hemostasis and further reduce mortality caused by uncontrolled bleeding. Furthermore, CCP wound dressings have an excellent antibacterial ability, which could be beneficial to inhibit wound inflammatory over-reaction and promote normal wound healing. Combined together, the prepared wound dressing in this research effort is expected to have high-potential in clinical applications.     

Efficacy of chitin-PAA-GTMAC gel in promoting wound healing: animal study

Acrylic grafted chitin (chitin-PAA) was modified with glycidyltrimethylammonium chloride (GTMAC) with the aim of promoting wound healing. The chitin-PAA-GTMAC gels with different GTMAC contents were compared with the original chitin-PAA gel and Intrasite gel for their efficacy in deep wound healing of Wistar rats. Four full-thickness wounds were made on the dorsal skin of rats and then each was treated with 4 materials; chitin-PAA, chitin-PAA-GTMAC(1:4), chitin-PAA-GTMAC(1:10) and Intrasite gel. During 18 days of treatment, the wounds were visually observed and calculated for wound size using image analysis program. Skin wound tissues of sacrificed rats were processed for routine histological observation and immunohistochemistry of proliferating cell nuclear antigen (PCNA). The wounds covered with the chitin derivatives either with or without GTMAC showed a significant reduction in wound size in day 9 in comparison with day 12 for those covered with Intrasite gel. The faster rate and the better pattern of epidermal development observed in histological study as well as the higher dermal cell proliferation (PCNA expression) also demonstrated the better efficiency in wound healing of the chitin derivatives than Intrasite. The earliest epidermal development of the wounds treated with chitin-PAA-GTMAC (1:4) among the tested materials suggested the most promising of this material for the treatment of full-thickness open wound.     

Isothermal crystallization kinetics and morphology of biodegradable poly(3-hydroxybutyrate-co-4-hydroxybutyrate)

Isothermal crystallization kinetics and morphology of poly(3-hydroxybutyrate-co-4-hydroxybutyrate) [P(3HB-co-4HB)] with different 4-hydroxybutyrate (4HB) molar fraction were investigated by differential scanning calorimetry (DSC), wide angle X-ray diffraction (WAXD), and polarized optical microscopy (POM). The results show that the crystallization mechanism and crystal structure of P(3HB-co-4HB) copolymers are the similar as those of poly(3-hydroxybutyrate) (PHB). While the equilibrium melting point and crystallization rate decrease with the increase of 4HB molar fraction. Banded spherulites are observed in neat PHB and P(3HB-co-4HB) copolymers, and morphology is influenced apparently by the crystallization temperature and 4HB unit.     

Development of nanotechnology for advancement and application in wound healing: a review

Wound healing is a series of different dynamic and complex phenomena. Many studies have been carried out based on the type and severity of wounds. However, to recover wounds faster there are no suitable drugs available, which are highly stable, less expensive as well as has no side effects. Nanomaterials have been proven to be the most promising agent for faster wound healing among all the other wound healing materials. This review briefly discusses the recent developments of wound healing by nanotechnology, their applicability and advantages. Nanomaterials have unique physicochemical, optical, and biological properties. Some of them can be directly applied for wound healing or some of them can be incorporated into scaffolds to create hydrogel matrix or nanocomposites, which promote wound healing through their antimicrobial, as well as selective anti‐ and pro‐inflammatory, and proangiogenic properties. Owing to their high surface area to volume ratio, nanomaterials have not only been used for drug delivery vectors but also can affect wound healing by influencing collagen deposition and realignment and provide approaches for skin tissue regeneration.Inspec keywords: skin, wounds, cellular biophysics, drug delivery systems, tissue engineering, hydrogels, nanocomposites, proteins, nanomedicineOther keywords: wound healing materials, nanomaterials, nanotechnology, proangiogenic properties, proinflammatory properties, collagen deposition, drug delivery vectors, skin tissue regeneration     

Effect of pore size and cross-linking of a novel collagen-elastin dermal substitute on wound healing

Collagen-elastin (CE) scaffolds are frequently used for dermal replacement in the treatment of full-thickness skin defects such as burn wounds. But little is known about the optimal pore size and level of cross-linking. Different formulations of dermal substitutes with unidirectional pores were tested in porcine full-thickness wounds in combination with autologous split skin mesh grafts (SSG). Effect on wound healing was evaluated both macro- and microscopically. CE scaffolds with a pore size of 80 or 100 μm resulted in good wound healing after one-stage grafting. Application of scaffolds with a larger average pore size (120 μm) resulted in more myofibroblasts and more foreign body giant cells (FBGC). Moderate crosslinking impaired wound healing as it resulted in more wound contraction, more FBGC and increased epidermal thickness compared to no cross-linking. In addition, take rate and redness were negatively affected compared to SSG only. Vascularization and the number of myofibroblasts were not affected by cross-linking. Surprisingly, stability of cross-linked scaffolds was not increased in the wound environment, in contrast to in vitro results. Cross-linking reduced the proliferation of fibroblasts in vitro, which might explain the reduced clinical outcome. The non-cross-linked CE substitute with unidirectional pores allowed one-stage grafting of SSG, resulting in good wound healing. In addition, only a very mild foreign body reaction was observed. Cross-linking of CE scaffolds negatively affected wound healing on several important parameters. The optimal non-cross-linked CE substitute is a promising candidate for future clinical evaluation.     

On-Demand Removable Self-Healing and pH-Responsive Europium-Releasing Adhesive Dressing Enables Inflammatory Microenvironment Modulation and Angiogenesis for Diabetic Wound Healing

Current diabetic wound treatments remain unsatisfactory due to the lack of a comprehensive strategy that can integrate strong applicability (tissue adhesiveness, shape adaptability, fast self-healability, and facile dressing change) with the initiation and smooth connection of the cascade wound healing processes. Herein, benefiting from the multifaceted bonding ability of tannic acid to metal ions and various polymers, a family of tannin–europium coordination complex crosslinked citrate-based mussel-inspired bioadhesives (TE-CMBAs) are specially developed for diabetic wound healing. TE-CMBAs can gel instantly (< 60 s), possess favorable shape-adaptability, considerable mechanical strengths, high elasticity, considerable wet tissue adhesiveness (≈40 kPa), favorable photothermal antimicrobial activity, excellent anti-oxidant activity, biocompatibility, and angiogenetic property. The reversible hydrogen bond crosslinking and sensitive metal–phenolic coordination also confers TE-CMBAs with self-healability, pH-responsive europium ion and TA releasing properties and on-demand removability upon mixing with borax solution, enabling convenient painless dressing change and the smooth connection of inflammatory microenvironment modulation, angiogenesis promotion, and effective extracellular matrix production leveraging the acidic pH condition of diabetic wounds. This adhesive dressing provides a comprehensive regenerative strategy for diabetic wound management and can be extended to other complicated tissue healing scenarios.     

Poly (ɛ‐caprolactone)–chitosan–poly (vinyl alcohol) nanofibrous scaffolds for skin excisional and burn wounds in a canine model

Poly (ɛ‐caprolactone)–chitosan–poly (vinyl alcohol) (PCL: Cs: PVA) nanofibrous blend scaffolds were known as useful materials for skin wound healing and would help the healing process about 50% faster at the final time point. From the previous studies by the authors, PCL: Cs: PVA (in 2: 1: 1.5 mass ratio) nanofibres showed high efficacy in healing on rat models. In this study, the scaffolds were examined in burn and excision wounds healing on dogs as bigger models. The scaffolds were applied on dorsum skin wounds (n  = 5) then macroscopic and microscopic investigations were carried out to measure the wounds areas and to track healing rate, respectively. Macroscopic results showed good aspect healing effect of scaffolds compared with control wounds especially after 21 days post‐operating for both cutting and burn wounds. Pathological studies showed that the healing rates of the wounds covered with PCL: Cs: PVA nanofibrous scaffolds were much rapid compared to untreated wounds in control group. The immunogenicity of the scaffolds in canine model was also investigated. The findings showed that nanofibrous blend scaffolds was not immunogenic in humoural immune responses. All these results indicated that PCL: Cs: PVA nanofibrous web could be considered as promising materials for wounds healings.Inspec keywords: nanofibres, nanomedicine, biomedical materials, polymer fibres, polymer blends, skin, woundsOther keywords: poly(ε‐caprolactone)‐chitosan‐poly (vinyl alcohol) nanofibrous blend scaffolds, skin excisional wounds, burn wounds, canine model, skin wound healing, dorsum skin wounds, macroscopic investigations, microscopic investigations, healing rate, cutting wounds, pathological study, humoural immune responses, nanofibrous web, immunogenicity, time 21 day     

The influence of a PHI-5-loaded silicone membrane,on cutaneous wound healing in vivo

This study investigated whether a novel ionogenic substance, containing amongst others zinc and rubidium (PHI-5; Dermagenics Inc, Memphis, TN, USA), could improve the healing of full-thickness skin wounds. Uniform wounds were created on the right flank of guinea pigs. Micro-grooved silicone rubber membranes, containing 0 (controls), 1.25, 5.00, or 10.00 μg PHI-5, were sutured onto this wound. Standardized digital wound photographs were made after 1, 3, and 6 weeks. Also, wound biopsies were taken after 3 and 6 weeks for histological and histomorphometrical evaluation. For all study groups, 6 animals were used. Analysis of the 1-week digital photographs showed that the surface area of the wounds decreased significantly, with an increasing PHI-5 concentration. No other differences were found in the wound photographs. Also, no differences were measured in histomorphometry at 3 and 6 weeks. Concluding, in our study model a single application of PHI-5 did have a significant positive influence on initial wound healing.     

Antibiotic eluting clay mineral (Laponite®) for wound healing application: an in vitro study

Different materials in form of sponge, hydrogel and film have been developed and formulated for treating and dressing burn wounds. In this study, the potential of Laponite, a gel forming clay, in combination with an antimicrobial agent (mafenide), as a wound dressing material was tested in vitro. Laponite/mafenide (Lap/Maf) hydrogel was formulated in three different ratios of Lap/Maf 1:1, 1:2, 1:3. Laponite/mafenide/alginate (Lap/Maf/Alg) film was also formulated by combining Lap/Maf gel (1:1) with alginate. Intercalation rate of mafenide into the layers of Laponite nanoparticles and physico-chemical properties, including wound dressing characteristics of materials were studied using various analytical methods. Furthermore, the degradation of materials and the release profile of mafenide were investigated in simulated wound exudates fluid and antibacterial effectiveness of the eluted mafenide was tested on a range of bacterial species. The cytotoxicity of materials was also evaluated in skin fibroblast culture. The results showed that mafenide molecules were intercalated between the nano-sized layers of Laponite. The eluted mafenide showed active antibacterial effects against all three tested bacteria. All intercalated mafenide released from Lap/Maf 1:1 and 1:2 gel formulations and nearly 80 % release from 1:3 formulation during test period. No significant difference was observed in release profile of mafenide between Lap/Maf/Alg film and Lap/Maf formulations. Wound dressing tests on Lap/Maf/Alg film showed it is a breathable dressing and has capacity to absorb wound exudates. The study showed that prepared Lap/Maf composite has the potential to be used as an antibiotic eluting gel or film for wound healing application. Additionally, Laponite has shown benefits in wound healing processes by releasing Mg²⁺ ions and thereby reducing the cytotoxic effect of mafenide on fibroblast cells.     

SiO2/聚（3-羟基丁酸酯-co-4-羟基丁酸酯）薄膜研究

目的研究纳米SiO2对可生物降解聚(3-羟基丁酸酯-co-4-羟基丁酸酯)(P34HB)包装膜结晶行为和力学性能的影响。方法采用溶液浇铸法制备SiO_2/P34HB纳米复合薄膜,利用红外光谱仪(FTIR)、扫描电镜(SEM)、正置热台显微镜(POM)、差示扫描量热仪(DSC)和万能力学试验机等研究纳米SiO_2对P34HB结构、结晶性和力学性能等的影响。结果纳米SiO_2在P34HB中起到异相成核的作用,SiO2/P34HB复合膜的结晶速率和结晶度得到明显改善。相比P34HB包装膜,当纳米SiO_2质量分数为2%时,SiO_2/P34HB复合膜的弹性模量和拉伸强度分别提高了72.7%和60.9%。结论获得了纳米SiO2改善可生物降解聚(3-羟基丁酸酯-co-4-羟基丁酸酯)包装膜结晶度和力学性能的最佳掺杂比例参数。     

Evaluation of bacterial nanocellulose-based uniform wound dressing for large area skin transplantation

Bacterial nanocellulose (BNC) was biosynthesized by Gluconacetobacter xylinus. The surface area, physicochemical structure and morphology of the materials were characterized. Here provides a method for an efficient production of uniform BNC, which is beneficial for the fast characterization and evaluation of BNC. In vitro cytotoxicity of the materials was evaluated by the proliferation, the adhesion, the viability and the morphology of NIH/3T3 cells. Low cytotoxicity of the BNC was observed, and micrographs demonstrate a good proliferation and adhesion of NIH/3T3 cells on BNC. Large area full-thickness skin defects were made on the back of C57BL/6 mice in animal surgery. The wounds were transplanted with BNC films and the results compared to those in a control group. The rehabilitation of the wound surfaces and the pathological sections of mice were investigated and are discussed. Histological examinations demonstrated faster and better healing effect and lower inflammatory response in the BNC group than those in the control group. Preliminary results on wound dressings from BNC show a curative effect promoting the healing of epithelial tissue. BNC is a promising natural polymer with medical applications in wound dressings.