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.     

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.     

Wound healing evaluation of sodium fucidate-loaded polyvinylalcohol/sodium carboxymethylcellulose-based wound dressing

The cross-linked hydrogel films containing sodium fucidate were previously reported to be prepared polyvinyl alcohol (PVA) and sodium carboxymethylcellulose (Na-CMC) using the freeze-thawing method and their physicochemical property was investigated. For the development of novel sodium fucidate-loaded wound dressing, here its in vivo wound healing test and histopathology were performed compared with the conventional ointment product. In wound healing test, the sodium fucidate-loaded composed of 2.5% PVA, 1.125% Na-CMC and 0.2% drug showed faster healing of the wound made in rat dorsum than the hydrogel without drug, indicating the potential healing effect of sodium fucidate. Furthermore, from the histological examination, the healing effect of sodium fucidate-loaded hydrogel was greater than that of the conventional ointment product and hydrogel without drug, since it might gave an adequate level of moisture and build up the exudates on the wound area. Thus, the sodium fucidate-loaded wound dressing composed of 5% PVA, 1.125% Na-CMC and 0.2% drug is a potential wound dressing with excellent wound healing.     

Development of a novel antimicrobial seaweed extract-based hydrogel wound dressing

The objective of this study was to develop a novel antimicrobial seaweed wound dressing. The seaweed extract was active against nine clinically-relevant wound pathogens. A hydrogel formulation was prepared using polyvinyl alcohol (PVA) and polyvinylpyrrolidone (PVP), followed by addition of 1% seaweed extract. The antimicrobial properties of the novel dressing were tested using agar diffusion assays, with release-profiles examined using gel leaching and gel transfer assays. The dressing was found to be effective against the same microbial strains as the seaweed extract, with similar efficacy to the commonly used silver-based dressing, Acticoat^®. Antimicrobial release-profile assays revealed that the dressing was effective in inhibiting 70–90% of the bacterial population within the first 30 min, followed by a long, sustained released up to 97 h, without leaving a residue following five subsequent transfers of the dressing. Antimicrobial activity was stable for up to 6 months of storage at 4 °C, but activity was reduced slightly after 15 weeks. Following autoclave sterilization, the dressing displayed a slower release profile compared to a non-autoclaved counterpart. Hence, the seaweed dressing may have commercial applications, potentially competing with silver-based dressings at a lower cost per-application. This is the first report of development of a seaweed-based antimicrobial dressing.     

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.     

阿立哌唑缓释微球的工艺优化及体内药动学研究

目的:制备阿立哌唑缓释微球,使用星点设计-效应面法优化工艺,并对其体内血药浓度进行分析。方法:采用乳化溶剂挥发法制备阿立哌唑微球;以油相二氯甲烷体积、水相聚乙烯醇质量分数及乳化转速为自变量,以微球的平均粒径、跨距、载药量、包封率、产率及突释量为因变量,对制备工艺进行优化,并对优化后的工艺进行验证。采用HPLC法测定家兔血浆中药物浓度。结果:最佳工艺为二氯甲烷体积1.62mL,聚乙烯醇质量分数1.91%,乳化转速2 161 r.min-1;按优化工艺制备的微球外观圆整、流动性好;平均粒径为41.54μm,跨距为1.01,载药量为18.82%,包封率为75.39%,产率为85.17%,突释为1.68%。自制微球制剂在家兔体内d 1有少量的突释,d 5～d 20维持较稳定的血药浓度,缓慢释放,之后浓度开始下降。结论:所优化的制备工艺重现性好,简单易行;星点设计-效应面法优化微球制备工艺预测性良好,所制备的微球具有较好的体外缓释特性;阿立哌唑缓释微球在家兔体内缓慢释放,该释药行为达到了预期的目的。     

Delivery of Therapeutics from Layer-by-Layer Electrospun Nanofiber Matrix for Wound Healing: An Update

Increasing incidences of chronic wounds urge the development of effective therapeutic wound treatment. As the conventional wound dressings are found not to comply with all the requirements of an ideal wound dressing, the development of alternative and effective dressings is demanded. Over the past few years, electrospun nanofiber has been recognized as a better system for wound dressing and hence has been studied extensively. Most of the electrospun nanofiber dressings were fabricated as single-layer structure mats. However, this design is less favorable for the effective healing of wounds mainly due to its burst release effect. To address this problem and to simulate the organized skin layer's structure and function, a multilayer structure of wound dressing had been proposed. This design enables a sustained release of the therapeutic agent(s), and more resembles the natural skin extracellular matrix. Multilayer structure is also referred to layer-by-layer (LbL), which has been established as an innovative method of drug incorporation and delivery, combines a high surface area of electrospun nanofibers with the multilayer structure mat. This review focuses on LbL multilayer electrospun nanofiber as a superior strategy in designing an optimal wound dressing.     

Drug-Loaded Polymeric Composite Skin Graft for Infection-Free Wound Healing: Fabrication, Characterization, Cell Proliferation, Migration, and Antimicrobial Activity

Purpose

A new, injectable, drug-loaded composite graft was developed to enable infection free wound healing.

Methods

The graft was fabricated using gentamicin and biomimetic microparticulate scaffolds in gelatin gel and characterized for biologically relevant properties like fluid uptake, evaporative water loss (EWL), water vapor transmission rate (WVTR), Young’s modulus and degradation. It was evaluated for drug release, cytocompatibility and antimicrobial efficacy against Staphylococcus aureus and Pseudomonas aeruginosa.

Results

Graft exhibited fluid uptake of 13.79%, EWL of 60–70% in 10?h, WVTR of 5480.31?g/m²/d, and Young’s modulus as 2.1–10.8?kPa. It exhibited 99.36% degree of crosslinking and a dual degradation behavior wherein, the carrier gel, gelatin, degraded rapidly leaving the microparticulate scaffolds intact. Drug release studies showed a sustained release of gentamicin for 13?days sufficient to inhibit the infection at the wound site. Cytocompatibility assessment of the graft revealed that graft supported cell adhesion, proliferation and migration. The antibacterial efficacy of the graft was assessed using Kirby-Bauer method and time kill assay, wherein results indicated a quick, effective (≥5-log reduction in CFU/ml) and long lasting antimicrobial effect.

Conclusions

These results as a whole indicate that the graft represents an effective alternative for infection-free healing of full thickness wounds.

Stabilization and encapsulation of a staphylokinase variant (K35R) into poly(lactic-co-glycolic acid) microspheres

The aim of this study is to prepare poly(lactic-co-glycolic acid) (PLGA) microspheres containing a staphylokinase variant K35R (DGR) with purpose of preserving the protein stability during both encapsulation and drug release. DGR-loaded microspheres are fabricated using a double-emulsion solvent extraction technique. Prior to encapsulation, the effect of ultrasonication emulsification of DGR solutions with methylene chloride on protein recovery was investigated. Moderate ultrasonic treatment of aqueous DGR/dichloromethane mixtures caused approximately 84% DGR aggregation. Polyvinyl alcohol (PVA) added into aqueous DGR solutions significantly improved DGR recovery to >90%. The effects of co-encapsulated PVA and NaCl in the external aqueous phase on the characteristics of the microspheres were investigated. When 2% PVA was co-encapsulated and 2.5% NaCl was added to the external water phase, DGR encapsulation efficiency was significantly increased from 7.1% to 78.1% and DGR was distributed uniformly throughout the microspheres. In vitro release test showed that DGR was released from PLGA microspheres in a sustained manner over 15 days. A large amount of released DGR was inactive in the absence of co-encapsulated PVA. On the contrary, when 2% PVA was co-encapsulated, the released DGR was almost completely intact within 9 days. In conclusion, PLGA microspheres can be an effective carrier for DGR and form a promising depot system.     

Wound healing dressings and drug delivery systems: a review

The variety of wound types has resulted in a wide range of wound dressings with new products frequently introduced to target different aspects of the wound healing process. The ideal dressing should achieve rapid healing at reasonable cost with minimal inconvenience to the patient. This article offers a review of the common wound management dressings and emerging technologies for achieving improved wound healing. It also reviews many of the dressings and novel polymers used for the delivery of drugs to acute, chronic and other types of wound. These include hydrocolloids, alginates, hydrogels, polyurethane, collagen, chitosan, pectin and hyaluronic acid. There is also a brief section on the use of biological polymers as tissue engineered scaffolds and skin grafts. Pharmacological agents such as antibiotics, vitamins, minerals, growth factors and other wound healing accelerators that take active part in the healing process are discussed. Direct delivery of these agents to the wound site is desirable, particularly when systemic delivery could cause organ damage due to toxicological concerns associated with the preferred agents. This review concerns the requirement for formulations with improved properties for effective and accurate delivery of the required therapeutic agents. General formulation approaches towards achieving optimum physical properties and controlled delivery characteristics for an active wound healing dosage form are also considered briefly.     

Development of polyvinyl alcohol-sodium alginate gel-matrix-based wound dressing system containing nitrofurazone

Polyvinyl alcohol (PVA)/sodium alginate (SA) hydrogel matrix-based wound dressing systems containing nitrofurazone (NFZ), a topical anti-infective drug, were developed using freeze-thawing method. Aqueous solutions of nitrofurazone and PVA/SA mixtures in different weight ratios were mixed homogeneously, placed in petri dishes, freezed at -20 degrees C for 18h and thawed at room temperature for 6h, for three consecutive cycles, and evaluated for swelling ratio, tensile strength, elongation and thermal stability of the hydrogel. Furthermore, the drug release from this nitrofurazone-loaded hydrogel, in vitro protein adsorption test and in vivo wound healing observations in rats were performed. Increased SA concentration decreased the gelation%, maximum strength and break elongation, but it resulted into an increment in the swelling ability, elasticity and thermal stability of hydrogel film. However, SA had insignificant effect on the release of nitrofurazone. The amounts of proteins adsorbed on hydrogel were increased with increasing sodium alginate ratio, indicating the reduced blood compatibility. In vivo experiments showed that this hydrogel improved the healing rate of artificial wounds in rats. Thus, PVA/SA hydrogel matrix based wound dressing systems containing nitrofurazone could be a novel approach in wound care.     

Accelerated wound healing and anti-inflammatory effects of physically cross linked polyvinyl alcohol–chitosan hydrogel containing honey bee venom in diabetic rats

Diabetes is one of the leading causes of impaired wound healing. The objective of this study was to develop a bee venom-loaded wound dressing with an enhanced healing and anti-inflammatory effects to be examined in diabetic rats. Different preparations of polyvinyl alcohol (PVA), chitosan (Chit) hydrogel matrix-based wound dressing containing bee venom (BV) were developed using freeze–thawing method. The mechanical properties such as gel fraction, swelling ratio, tensile strength, percentage of elongation and surface pH were determined. The pharmacological activities including wound healing and anti-inflammatory effects in addition to primary skin irritation and microbial penetration tests were evaluated. Moreover, hydroxyproline, glutathione and IL-6 levels were measured in the wound tissues of diabetic rats. The bee venom-loaded wound dressing composed of 10 % PVA, 0.6 % Chit and 4 % BV was more swellable, flexible and elastic than other formulations. Pharmacologically, the bee venom-loaded wound dressing that has the same pervious composition showed accelerated healing of wounds made in diabetic rats compared to the control. Moreover, this bee venom-loaded wound dressing exhibited anti-inflammatory effect that is comparable to that of diclofenac gel, the standard anti-inflammatory drug. Simultaneously, wound tissues covered with this preparation displayed higher hydroxyproline and glutathione levels and lower IL-6 levels compared to control. Thus, the bee venom-loaded hydrogel composed of 10 % PVA, 0.6 % Chit and 4 % BV is a promising wound dressing with excellent forming and enhanced wound healing as well as anti-inflammatory activities.     

Notel长效微球制剂的制备和评价

目的：制备并评价Notel聚乳酸-羟基乙酸共聚物（PLGA）长效缓释微球。方法：采用乳化-溶剂挥发法制备Notel缓释微球,以载药量、包封率、体外释放为评价指标,考察高分子材料、高分子溶液浓度、硬脂酸、不同pH的聚乙烯醇（PVA）溶液等因素对微球的影响,筛选最优处方并制备微球,考察大鼠药动学及对db/db小鼠的降血糖作用。结果：按最优处方制备的微球形态圆整,平均粒径为60 μm,载药量12.5%,体外释药可达1个月。微球在大鼠体内1 h即有药物释放,第8天血药浓度达到峰值C_max（52.96±3.20） ng·mL^-1并持续释放30 d。db/db小鼠的空腹血糖浓度在1个月内有效降低。结论：Notel缓释微球作为1个月长效制剂治疗2型糖尿病（T2DM）具有良好的开发前景。     

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.     

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.     

Novel chitosan wound dressing loaded with minocycline for the treatment of severe burn wounds

Novel wound dressings composed of chitosan (CH) film and minocycline hydrochloride (MH) were prepared using commercial polyurethane film (Tegaderm) as a backing. CHs with deacetylation degrees of 67%, 83% and 96% (mol/mol), named CH67, CH83 and CH96, respectively, were used. Wound dressing with a large piece of Tegaderm film (4 cm × 4 cm), named CH-MH-N, and wound dressing prepared by cutting CH-MH-N to the wound size, named CH-MH-A, were developed. As CH67-MH-N and CH83-MH-N showed the sustained release of minocycline in vitro, CH67 and CH83 were used as chitosan in the in vivo studies. Various formulations were applied to severe burn wounds in rats in the early stage, and the wound status and change in the wound surface area were examined. The use of 10 mg of MH and complete sealing with Tegaderm had a negative effect. MH ointment was not effective, but Geben cream was fairly effective. However, CH83-MH-A containing 2 mg of MH (CH83-MH2-A) and CH83 film showed an excellent effect. Considering the elimination of pus, CH83-MH2-A tended to be better than CH83 film. CH83-MH2-A is suggested as a useful formulation for the treatment of severe burn wounds.     

Interactive Wound Dressings

Drugs & Aging - The properties of an ideal wound dressing do not change with the introduction of new types of wound dressing, but the range of effects on wound healing increases. The number of...     

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.     

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.