Development and characterization of a superabsorbing hydrogel film containing Ulmus davidiana var. Japonica root bark and pullulan for skin wound healing

Ulmus davidiana var. japonica (UD) has widely been used in Korean traditional medicine for the treatment of various types of diseases including inflammation and skin wounds. The UD root bark powders possess gelling activity with an excellent capacity for absorbing water. This distinct property could make the UD root bark powders to be a great material for manufacturing a gel film specifically for the healing of large and highly exudating wounds (e.g., pressure sores and diabetic ulcers). In this research, we separated the UD root bark powder into 4 different samples based on their sizes and then tested their water absorption capacity and flowability. Based on these results, 75–150 μm sized and below 75 μm sized samples of UD root bark powders were chosen, and UD gel films were prepared. The UD gel films showed good thermal stability and mechanically improved properties compared with pullulan only gel film with excellent swelling capacity and favorable skin adhesiveness. Further, in the animal studies with the skin wound mice model, the UD gel films exhibited significant therapeutic effects on accelerating wound closure and dermal regeneration. Overall, this study demonstrated the applicability of UD root bark powders for hydrogel wound dressing materials, and the potential of UD gel films to be superior wound dressings to currently available ones.     

An innovative bi-layered wound dressing made of silk and gelatin for accelerated wound healing

In this study, the novel silk fibroin-based bi-layered wound dressing was developed. Wax-coated silk fibroin woven fabric was introduced as a non-adhesive layer while the sponge made of sericin and glutaraldehyde-crosslinked silk fibroin/gelatin was fabricated as a bioactive layer. Wax-coated silk fibroin fabrics showed improved mechanical properties compared with the non-coated fabrics, but less adhesive than the commercial wound dressing mesh. This confirmed by results of peel test on both the partial- and full-thickness wounds. The sericin-silk fibroin/gelatin spongy bioactive layers showed homogeneous porous structure and controllable biodegradation depending on the degree of crosslinking. The bi-layered wound dressings supported the attachment and proliferation of L929 mouse fibroblasts, particularly for the silk fibroin/gelatin ratio of 20/80 and 0.02% GA crosslinked. Furthermore, we proved that the bi-layered wound dressings promoted wound healing in full-thickness wounds, comparing with the clinically used wound dressing. The wounds treated with the bi-layered wound dressings showed the greater extent of wound size reduction, epithelialization, and collagen formation. The superior properties of the silk fibroin-based bi-layered wound dressings compared with those of the clinically used wound dressings were less adhesive and had improved biological functions to promote cell activities and wound healing. This novel bi-layered wound dressing should be a good candidate for the healing of full-thickness wounds.     

Novel wound models for characterizing ibuprofen release from foam dressings

The purpose of the present study was to design and characterize low exudate level wound (LEW) and high exudate level wound (HEW) in vitro models by means of investigating therapeutic substance release from exudate-absorbing formulations. Biatain Ibu foam dressing was used to characterize in vitro release of ibuprofen within the models and also for in vitro-in vivo correlation (IVIVC) studies. Ibuprofen release was described by zero order rate constants of 0.0147 for 1 day and 0.0038 mg/cm(2) h for 3 days in HEW and LEW models, respectively. The release is suggested to be controlled by ibuprofen diffusion from the dressing in the HEW model, whereas fluid absorption is rate-limiting in the LEW model. Ibuprofen release, from Biatain Ibu foam dressings in vivo, is within the same ranges as in vitro. Thus, it is suggested that, depending on the level of exudate, the in vivo release of ibuprofen depends on ibuprofen diffusion from and absorption of exudates to the dressings. Consequently, both the HEW and LEW in vitro models should be applied in order to fully characterize ibuprofen release from Biatain Ibu foam dressings. Future studies may show whether these in vitro models can be used to characterize therapeutic substance release from exudate-absorbing formulations in general.     

Electrospun fibers with plasmid bFGF polyplex loadings promote skin wound healing in diabetic rats

Deep or chronic skin wounds are difficult to heal spontaneously due to the lack of scaffold to guide cell growth and reduced levels and activities of endogenous growth factors. Emulsion electrospinning process integrated with DNA condensation techniques indicated potentials to gradually release DNA, but no attempt has been made to clarify the advantages in promoting tissue regeneration and wound recovery. In this study, polyplexes of basic fibroblast growth factor-encoding plasmid (pbFGF) with poly(ethylene imine) were incorporated into electrospun fibers with a core-sheath structure, and poly(ethylene glycol) was included into the fiber sheath to allow a sustained release of pbFGF for 4 weeks. In vitro tests on mouse embryo fibroblasts indicated that pbFGF-loaded fibrous mats enhanced cell proliferation by the autocrine bFGF, and an effective cell transfection proceeded for over 28 days. Skin wounds were created in the dorsal area of diabetic rats for in vivo evaluation of skin regeneration after being covered with pbFGF-loaded fibrous mats. The gradual pbFGF release revealed significantly higher wound recovery rate with improved vascularization, enhanced collagen deposition and maturation, complete re-epithelialization and formation of skin appendages. The above results demonstrate the potential use of pbFGF-loaded electrospun fibrous mats to accelerate the healing of skin ulcers for patients with diabetic mellitus.     

Reduced cellular toxicity of a new silver-containing antimicrobial dressing and clinical performance in non-healing wounds

Bacterial colonisation of wounds may delay wound healing. Modern silver-containing dressings are antimicrobial, yet cellular toxicity is a serious side-effect. We provide data for a newly formulated silver-containing ointment dressing, Atrauman Ag, for antimicrobial activity and cytotoxicity. Atrauman Ag effectively killed a panel of commensal skin as well as pathogenic bacterial strains while cytotoxicity for HaCaT keratinocytes was only around 10%. With these favourable in vitro tests, Atrauman Ag was analysed in 86 patients with traumatic and non-healing wounds of different aetiologies. The wound state was evaluated for 3 subsequent dressing changes. The slough score was reduced from 59.2 to 35.8%, granulation tissue increased from 27 to 40% and epithelialisation went up from 12.1 to 24%. We conclude that Atrauman Ag has a superior profile of antimicrobial activity over cellular toxicity and the low silver ion release rate may prevent interference with wound-healing mechanisms.     

Wound Dressings Based on Chitosans and Hyaluronic Acid for the Release of Chlorhexidine Diacetate in Skin Ulcer Therapy

In the present work wound dressings, based on chitosan hydrochloride (HCS), 5-methyl-pyrrolidinone chitosan (MPC), and their mixtures with an anionic polymer, hyaluronic acid (HA), were prepared by freeze-drying. Chlorhexidine diacetate (CX) was used as an antimicrobic drug. The mechanical properties of the wound dressings were investigated. In particular, the wound dressings were subjected to dynamic hydration measurements to evaluate their capability to absorb wound exudate and to rheological analysis to investigate their resistance to mechanical stresses on hydration. The wound dressings were also characterized for drug release properties. The antioxidant and antimicrobial activities of medicated and non-medicated wound dressings were also investigated. All the wound dressings are characterized by mechanical resistance suitable for skin application. The addition of hyaluronic acid to chitosans leads to a reduction in wound dressing hydration properties and a modulation of drug release. The wound dressing based on MPC is characterized by the highest elastic properties and by the best scavenger activity. Antimicrobial activity against bacteria and C. albicans is shown by the dressing based on chitosan also in absence of chlorhexidine.     

Clinical Potential of a Silk Sericin-Releasing Bioactive Wound Dressing for the Treatment of Split-Thickness Skin Graft Donor Sites

Purpose

An ethyl alcohol-precipitated silk sericin/PVA scaffold that controlled the release of silk sericin was previously developed and applied for the treatment of full-thickness wounds in rats and demonstrated efficient healing. In this study, we aimed to further evaluate the clinical potential of this scaffold, hereafter called “silk sericin-releasing wound dressing”, for the treatment of split-thickness skin graft donor sites by comparison with the clinically available wound dressing known as “Bactigras®”.

Methods

In vitro characterization and in vivo evaluation for safety of the wound dressings were performed. A clinical trial of the wound dressings was conducted according to standard protocols.

Results

The sericin released from the wound dressing was not toxic to HaCat human keratinocytes. A peel test indicated that the silk sericin-releasing wound dressing was less adhesive than Bactigras®, potentially reducing trauma and the risk of repeated injury upon removal. There was no evidence of skin irritation upon treatment with either wound dressing. When tested in patients with split-thickness skin graft donor sites, the wounds treated with the silk sericin-releasing wound dressing exhibited complete healing at 12?±?5.0 days, whereas those treated with Bactigras® were completely healed at 14?±?5.2 days (p?=?1.99?×?10^?4). In addition, treatment with the silk sericin-releasing wound dressing significantly reduced pain compared with Bactigras® particularly during the first 4 postoperative days (p?=?2.70?×?10^?5 on day 1).

Conclusion

We introduce this novel silk sericin-releasing wound dressing as an alternative treatment for split-thickness skin graft donor sites.     

Antimicrobial PLGA ultrafine fibers: Interaction with wound bacteria

The structure and functions of polymer nanofibers as wound dressing materials have been well investigated over the last few years. However, during the healing process, nanofibrous mats are inevitably involved in dynamic interactions with the wound environment, an aspect not explored yet. Potential active participation of ultrafine fibers as wound dressing material in a dynamic interaction with wound bacteria has been examined using three wound bacterial strains and antimicrobial fusidic acid (FA)-loaded electrospun PLGA ultrafine fibers (UFs). These were developed and characterized for morphology and in-use pharmaceutical attributes. In vitro microbiological studies showed fast bacterial colonization of UFs and formation of a dense biofilm. Interestingly, bacterial stacks on UFs resulted in a remarkable enhancement of drug release, which was associated with detrimental changes in morphology of UFs in addition to a decrease in pH of their aqueous incubation medium. In turn, UFs by allowing progressively faster release of bioactive FA eradicated planktonic bacteria and considerably suppressed biofilm. Findings point out the risk of wound reinfection and microbial resistance upon using non-medicated or inadequately medicated bioresorbable fibrous wound dressings. Equally important, data strongly draw attention to the importance of characterizing drug delivery systems and establishing material-function relationships for biomedical applications under biorelevant conditions.     

Wound dressings based on chitosans and hyaluronic acid for the release of chlorhexidine diacetate in skin ulcer therapy

In the present work wound dressings, based on chitosan hydrochloride (HCS), 5-methyl-pyrrolidinone chitosan (MPC), and their mixtures with an anionic polymer, hyaluronic acid (HA), were prepared by freeze-drying. Chlorhexidine diacetate (CX) was used as an antimicrobic drug. The mechanical properties of the wound dressings were investigated. In particular, the wound dressings were subjected to dynamic hydration measurements to evaluate their capability to absorb wound exudate and to rheological analysis to investigate their resistance to mechanical stresses on hydration. The wound dressings were also characterized for drug release properties. The antioxidant and antimicrobial activities of medicated and non-medicated wound dressings were also investigated. All the wound dressings are characterized by mechanical resistance suitable for skin application. The addition of hyaluronic acid to chitosans leads to a reduction in wound dressing hydration properties and a modulation of drug release. The wound dressing based on MPC is characterized by the highest elastic properties and by the best scavenger activity. Antimicrobial activity against bacteria and C. albicans is shown by the dressing based on chitosan also in absence of chlorhexidine.     

Development of polyurethane foam dressing containing silver and asiaticoside for healing of dermal wound

 Polyurethane foam dressings for dermal wounds were formulated with natural polyols in order to improve the foam characteristics and the release of 2 active agents, silver and asiaticoside (AS) as an antimicrobial agent and an herbal wound healing agent, respectively. The foam was instantly formed by interaction of polyols and diisocyanate. Hydroxypropyl methylcellulose, chitosan and sodium alginate were individually mixed with the main polyols, polypropylene glycol, in the formulation while the active components were impregnated into the obtained foam dressing sheets. Although the type and amount of the natural polyols slightly affected the pore size, water sorption-desorption profile and compression strength of the obtained foam sheets, a prominent effect was found in the release of both active components. Among natural polyols formulations, foam sheets with alginate showed the highest silver and AS release. Non-cytotoxicity of these foam sheets to human fibroblast cells was confirmed. Antimicrobial testing on four bacteria strains showed that 1 mg/cm2 silver in formulations with 6% of natural polyols and without natural polyols had sufficient content of the silver release with comparable inhibition zone and significantly larger zone than other formulations. In pig study, the foam dressing with 6% alginate, 1 mg/cm2 silver and 5% AS could improve wound healing in both the percentage of the wound closure and histological parameters of the dermal wound without any dermatologic reactions. In conclusion, this innovative foam dressing had potential to be a good candidate for wound treatment.     

Bioburden-responsive antimicrobial PLGA ultrafine fibers for wound healing

Despite innovation in the design and functionalization of polymer nanofiber wound healing materials, information on their interaction with the biochemical wound environment is lacking. In an earlier study, we have reported the interaction of fusidic acid-loaded PLGA ultrafine fibers (UFs) with wound bacteria. Massive bacterial colonization and the formation of a dense biofilm throughout the mat were demonstrated. This was associated with a marked enhancement of initial drug release at concentrations allowing eradication of planktonic bacteria and considerable suppression of biofilm. The present study aimed at extending earlier findings to gain more mechanistic insights into the potential response of the fusidic acid-laden UFs under study to controlled microbial bioburden. Initial drug release enhancement was shown to involve surface erosion of the ultrafibrous mats likely mediated by microbial esterase activity determined in the study. Release data could be correlated with microbial bioburden over the inoculum size range 10³-10⁷ CFU/ml, suggesting a bioburden-triggered drug release enhancement mechanism. Moreover, the effectiveness of fusidic acid-laden UFs in the healing of either lightly contaminated or Staphylococcus aureus heavily infected wounds in a rat model suggested in-use relevant antimicrobial release patterns. Findings indicated active participation of polymer ultrafine wound dressings in a dynamic interaction with the wound milieu, which affects their structure-function relationship. Understanding such an interaction is fundamental to the characterization and performance assessment of wound materials under biorelevant conditions and the design of polymer-based infection-responsive biomaterials.     

鱼油伤口护理软膏的制备及其对皮肤切线伤的促愈合作用

鱼油中的多不饱和脂肪酸具有促进皮肤损伤修复的功能。以富含多不饱和脂肪酸的鱼油为原料，复配黄凡士林、液体石蜡，制备油性伤口护理软膏敷料。测试了该软膏敷料的细胞相容性、阻水性、阻菌性及其对Sprague Dawley（SD）大鼠切线伤的促愈合作用。结果表明，软膏浸提液培养的L929细胞相对存活率为（99.5 ± 2.2）%，具有优异的细胞相容性；软膏具有优异的阻水性和阻菌性；在切线伤护理中，所制备膏状敷料能够促进创面胶原的沉积与重排，减轻瘢痕的生成。鱼油伤口护理软膏在浅表性皮肤创面护理方面有着良好的应用前景。     

Hyaluronic acid and chitosan-based nanosystems: a new dressing generation for wound care

ABSTRACT

Introduction: The main goal in the management of chronic wounds is the development of multifunctional dressings able to promote a rapid recovery of skin structure and function, improving patient compliance.

Areas covered: This review discusses the use of nanosystems, based on hyaluronic acid and chitosan or their derivatives for the local treatment of chronic wounds. The bioactive properties of both polysaccharides will be described, as well as the results obtained in the last decade by the in vitro and in vivo evaluation of the wound healing properties of nanosystems based on such polymers.

Expert opinion: In the last decades, there has been a progressive change in the local treatments of chronic wounds: traditional inert dressings have been replaced by more effective bioactive ones, based on biopolymers taking part in wound healing and able to release the loaded active agents in a controlled way. With the advance of nanotechnologies, the scenario has further changed: nanosystems, characterized by a large area-to-volume ratio, show an improved interaction with the biological substrates, amplifying the activity of the constituent biopolymers. In the coming years, a deeper insight into wound healing mechanisms and the development of new techniques for nanosystem manufacturing will results in the design of new scaffolds with improved performance.     

Enhancing dermal matrix regeneration and biomechanical properties of 2nd degree-burn wounds by EGF-impregnated collagen sponge dressing

To better define the relationship between dermal regeneration and wound contraction and scar formation, the effects of epidermal growth factor (EGF) loaded in collagen sponge matrix on the fibroblast cell proliferation rate and the dermal mechanical strength were investigated. Collagen sponges with acid-soluble fraction of pig skin were prepared and incorporated with EGF at 0, 4, and 8 microg/1.7 cm2. Dermal fibroblasts were cultured to 80% confluence using DMEM, treated with the samples submerged, and the cell viability was estimated using MTT assay. A deep, 2nd degree- burn of diameter 1cm was prepared on the rabbit ear and the tested dressings were applied twice during the 15-day, post burn period. The processes of re-epithelialization and dermal regeneration were investigated until the complete wound closure day and histological analysis was performed with H-E staining. EGF increased the fibroblast cell proliferation rate. The histology showed well developed, weave-like collagen bundles and fibroblasts in EGF-treated wounds while open wounds showed irregular collagen bundles and impaired fibroblast growth. The breaking strength (944.1 +/- 35.6 vs. 411.5 +/- 57.0 Fmax, gmm(-2)) and skin resilience (11.3 +/- 1.4 vs. 6.5 +/- 0.6 mJ/mm2) were significantly increased with EGF-treated wounds as compared with open wounds, suggesting that EGF enhanced the dermal matrix formation and improved the wound mechanical strength. In conclusion, EGF-improved dermal matrix formation is related with a lower wound contraction rate. The impaired dermal regeneration observed in the open wounds could contribute to the formation of wound contraction and scar tissue development. An extraneous supply of EGF in the collagen dressing on deep, 2nd degree-burns enhanced the dermal matrix formation.     

自组装纤维支架肽对深Ⅱ度烧伤创面收缩作用的实验研究

目的：探讨纳米短肽对深Ⅱ度烧伤创面的收缩及创面表皮的再生作用。方法：以电力机械烧伤法在雌性SD大鼠背部制造皮肤深Ⅱ度烫伤模型。烧伤后分别以不同生物辅料处理创面,以起到治疗作用。全程记录处理伤口的大体形态学变化。分别在手术后7、10、14、21 d以创面描记及数字图像处理软件系统描述创面生长情况。结果：与对照组生物敷料比较,这种自组装纤维支架肽可以加速缩短焦痂的的形成3～5 d时间,并加速伤口的收缩达20%～30%的水平。结论：自组装纤维支架肽对深度烧伤创面收缩具有促进作用。     

Wound dressings containing bFGF-impregnated microspheres

The primary objective was to synthesize a novel wound dressing containing basic fibroblast growth factor (bFGF)-loaded microspheres for promoting healing and tissue regeneration. Gelatin sponge was chosen as the underlying layer and elastomeric polyurethane membranes were used as the external layer. To achieve prolonged release, bFGF addition was loaded in microspheres. The microspheres were characterized for particle size, in vitro protein release and bioactivity. The bilayer dressings were tested in in vivo experiments on full-thickness skin defects created on pigs. Average size of the microspheres was 14.36 +/- 3.56 microm and the network sponges were characterized with an average pore size of 80-160 microm. Both the in vitro release efficiency and the protein bioactivity revealed that bFGF was released in a controlled manner and it was biologically active as assessed by its ability to induce the proliferation of fibroblasts. It was observed that sustained release of bFGF provided a higher degree of reduction in the wound areas. Histological investigations showed that the dressings were biocompatible and did not cause any mononuclear cell infiltration or foreign body reaction. The structure of the newly formed dermis was almost the same as that of the normal skin. The application of these novel bilayer wound dressings provided an optimum healing milieu for the proliferating cells and regenerating tissues in pig's skin defect models.     

美宝湿润烧伤膏在尿道下裂术后创面应用特点

目的探讨美宝湿润烧伤膏在尿道下裂术后创面应用特点及效果。方法在尿道下裂术后创面换药中,采用美宝湿润烧伤膏（MEBO）涂抹于创面,再用4—6层无菌纱布包扎,构成内层敷料（以下简称MEBO敷料）,并与采用普通凡士林纱作内层敷料包扎作比较。结果使用MEBO敷料作内层敷料在尿道下裂术后创面的换药中具有明显的防粘附、促进创面愈合作用;同时换药时间短,减少患儿痛苦,降低医疗费用等优点。结论应用MEBO敷料作为一种尿道下裂术后创面的包扎是较理想的改进物质。     

鱼皮胶原蛋白-壳聚糖复合海藻酸盐水凝胶敷料对烧烫伤创面的促愈合作用

本文以海藻酸钠为原料,复配壳聚糖、鱼皮胶原蛋白,通过Ca2+离子交联制备成海藻酸盐水凝胶敷料。测试了该敷料的物理机械性能及其对大白兔浅Ⅱ度烧烫伤创面的促愈合作用。结果表明：鱼皮胶原蛋白-壳聚糖复合海藻酸盐水凝胶的含水量≥80%,具有良好的吸湿保湿和机械性能,是一种理想的伤口创面敷料;对浅Ⅱ度烧烫伤的愈合周期远远少于医用纱布、市售聚氨酯水凝胶敷料,且能消除伤口炎症,抑制瘢痕的生成,在伤口护理方面有着良好的前景和应用方向。     

Preparation, Characterization, and Release of Amoxicillin from Electrospun Fibrous Wound Dressing Patches

Purpose

To produce electrospun polymeric fibrous wound dressing patches that can release the antibiotic drug amoxicillin in a controlled manner.

Methods

Poly(D,L-lactide-co-glycolide) acid (PLGA) fibrous dressings with entrapped amoxicillin were produced by electrospinning. The morphology and successful entrapment of amoxicillin in the PLGA fibrous dressings were validated by scanning electron microscopy (SEM) and Fourier Transform Infrared (FTIR) spectroscopy. The rate of drug release from the dressing patches was measured in various media for a period of 21 days using UV spectroscopy.

Results

PLGA fibres entrapping amoxicillin were collected for 300 s and then cut to form square patches with an average weight of 55 mg. Each dressing patch contained ~2 mg of amoxicillin. The mean fibre diameter was 2.2?±?0.4 μm. The drug release from the PLGA dressings was found to be different for each medium during the 21-day release period with the highest and lowest concentration of drug released observed when the dressings were immersed in simulated body fluid (SBF) and phosphate buffered saline (PBS), respectively.

Conclusions

The release profiles obtained in this study and the well-established biocompatibility of PLGA indicate that the fibre-based patches with entrapped amoxicillin fabricated in this work are very well suited for applications in wound healing and infection control.     

Controlled Release of Chitosan and Sericin from the Microspheres-Embedded Wound Dressing for the Prolonged Anti-microbial and Wound Healing Efficacy

One approach in wound dressing development is to incorporate active molecules or drugs in the dressing. In order to reduce the frequency of dressing changes as well as to prolong wound healing efficacy, wound dressings that can sustain the release of the active molecules should be developed. In our previous work, we developed chitosan/sericin (CH/SS) microspheres that released sericin in a controlled rate. However, the difficulty of applying the microspheres that easily diffuse and quickly degrade onto the wound was its limitations. In this study, we aimed to develop wound dressing materials which are easier to apply and to provide extended release of sericin. Different amounts of CH/SS microspheres were embedded into various compositions of polyvinyl alcohol/gelatin (PVA/G) scaffolds and fabricated using freeze-drying and glutaraldehyde crosslinking techniques. The obtained CH/SS microspheres-embedded scaffolds with appropriate design and formulation were introduced as a wound dressing material. Sericin was released from the microspheres and the scaffolds in a sustained manner. Furthermore, an optimized formation of the microspheres-embedded scaffolds (2PVA2G+2CHSS) was shown to possess an effective antimicrobial activity against both gram-positive and gram-negative bacteria. These microspheres-embedded scaffolds were not toxic to L929 mouse fibroblast cells, and they did not irritate the tissue when applied to the wound. Finally, probably by the sustained release of sericin, these microspheres-embedded scaffolds could promote wound healing as well as or slightly better than a clinically used wound dressing (Allevyn®) in a mouse model. The antimicrobial CH/SS microspheres-embedded PVA/G scaffolds with sustained release of sericin would appear to be a promising candidate for wound dressing application.