Plasma treated polyethylene grafted with adhesive molecules for enhanced adhesion and growth of fibroblasts

The cell–material interface plays a crucial role in the interaction of cells with synthetic materials for biomedical use. The application of plasma for tailoring polymer surfaces is of abiding interest and holds a great promise in biomedicine. In this paper, we describe polyethylene (PE) surface tuning by Ar plasma irradiating and subsequent grafting of the chemically active PE surface with adhesive proteins or motives to support cell attachment. These simple modifications resulted in changed polymer surface hydrophilicity, roughness and morphology, which we thoroughly characterized. The effect of our modifications on adhesion and growth was tested in vitro using mouse embryonic fibroblasts (NIH 3T3 cell line). We demonstrate that the plasma treatment of PE had a positive effect on the adhesion, spreading, homogeneity of distribution and moderately on proliferation activity of NIH 3T3 cells. This effect was even more pronounced on PE coated with biomolecules.     

EPDIM peptide-immobilized porous chitosan beads for enhanced wound healing: Preparation,characterizations and in vitro evaluation

EPDIM peptide is known to regulate cellular activities by interacting with α₃β₁ integrin, which can be contributed to wound healing process. In this study, EPDIM was immobilized onto three-dimensional porous chitosan beads (χtopore) as a scaffold for enhanced wound healing. The significant decrease in contact angle indicates that EPDIM immobilization could lead to the enhanced surface wettability after its immobilization. The immobilized EPDIM was fairly distributed along its surface and the morphology was maintained even after the reaction. The immobilized amount of EPDIM was found to be about 5.68 nmol/mg of χtopore by amino acid analysis. To verify the complete removal of coupling agents after EPDIM immobilization, each coupling agent was quantitatively analyzed by LC-MS. In vitro proliferation rates of both NIH 3T3 and HaCaT showed that EPDIM immobilization onto χtopore could significantly enhance the growth rate of both cells, while the unmodified χtopore did not increase in cell number even after 15 days of culture. Therefore, these results demonstrate that EPDIM peptide-immobilized χtopore can be utilized as an attractive scaffold for enhanced wound healing.     

Assessment of reinforced poly(ethylene glycol) chitosan hydrogels as dressings in a mouse skin wound defect model

Wound dressings of chitosan are biocompatible, biodegradable, antibacterial and hemostatic biomaterials. However, applications for chitosan are limited due to its poor mechanical properties. Here, we conducted an in vivo mouse angiogenesis study on reinforced poly(ethylene glycol) (PEG)-chitosan (RPC) hydrogels. RPC hydrogels were formed by cross-linking chitosan with PEGs of different molecular weights at various PEG to chitosan ratios in our previous paper. These dressings can keep the wound moist, had good gas exchange capacity, and was capable of absorbing or removing the wound exudate. We examined the ability of these RPC hydrogels and neat chitosan to heal small cuts and full-thickness skin defects on the backs of male Balb/c mice. Histological examination revealed that chitosan suppressed the infiltration of inflammatory cells and accelerated fibroblast proliferation, while PEG enhanced epithelial migration. The RPC hydrogels promoted wound healing in the small cuts and full layer wounds. The optimal RPC hydrogel had a swelling ratio of 100% and a water vapor transmission rate (WVTR) of about 2000 g/m²/day. In addition, they possess good mechanical property and appropriate degradation rates. Thus, the optimal RPC hydrogel formulation functioned effectively as a wound dressing and promoted wound healing.     

Poly(L-lactic acid) nanocylinders as nanofibrous structures for macroporous gelatin scaffolds

Electrospun Nanofiber sheets have been shown to mimic the structure of extracellular matrix (ECM). Although these nanofibers have shown great potential for use as tissue engineering scaffolds, it is difficult for the electrospun nanofiber based sheets to be shaped into the desired three-dimensional structure. In this study, poly(L-lactic acid) (PLLA), a biodegradable and biocompatible polyester, was electrospun to produce nanofibers that were treated with an amino group containing base in order to fabricate polymeric nanocylinders. The aspect ratio of the PLLA nanocylinders was tunable by varying the aminolysis time and density of the amino group containing base. The effects of changes in nanofibrous morphology of the PLLA nanocylinders/macro-porous gelatin scaffolds on cell adhesion and proliferation were evaluated. The results revealed different cell morphology, adhesion, and proliferation in the nanocylinders composite gelatin scaffold versus gelatin scaffold alone. Confocal laser scanning microscopy observation showed more spreading and a more flattened cell morphology after NIH3T3 cells were cultured on PLLA nanocylinders/gelatin scaffolds for 10 hours and 4 days. These results indicate that the gelatin/PLLA nanocylinder composite is a promising way to fabricate 3D nanofibrous scaffolds that accelerates cell adhesion and proliferation for tissue engineering.     

Hyaluronic acid and silver sulfadiazine-impregnated polyurethane foams for wound dressing application

Five different kinds of PU foam wound dressings were prepared to investigate their wound healing capability. They include (i) PU+silver sulfadiazine (AgSD), (ii) PU+alginate (Al), (iii) PU+Al+AgSD, (iv) PU+hyaluronic acid (HA), and (v) PU+HA+AgSD. Physical properties and in vitro behaviors of AgSD release and fibroblast adhesion on those dressings were evaluated. From the drug release and fibroblast adhesion studies, it was observed that PU foam impregnated with both HA and AgSD shows good drug release behavior and low adhesion of the cells. Furthermore, the HA and AgSD-containing PU foam showed excellent wound healing effect without any inflammation or yellow cluster. The wound size decreased around 77% after 1 week application of that foam dressing onto a rat skin defect.     

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.     

Adhesion and proliferation of fibroblasts on cluster-assembled nanostructured carbon films: the role of surface morphology

We have investigated the influence on adhesion and proliferation of NIH 3T3 fibroblasts of the surface morphology of cluster assembled carbon films deposited by Supersonic Cluster Beam Deposition. Nanostructured carbon films exhibit a multi-scale morphology, which resembles the surface structure of the extracellular matrix, and possess a high specific area, while being relatively smooth at all scales. Correlations between measured morphological parameters and adaptive cell response have been brought out. High specific area and smoothness appear to conceivably favour both the early attachment of plated cells and the long-term survival of adherent cells. Moreover, nano-structured carbon films affect the cells morphology as well as the extension and the number of the focal contacts.     

In vitro evaluation of biocompatibility of different wound dressing materials

The in vitro biocompatibility of newly developed wound dressings consisting of different chitosan salts (chitosan lactate, glutamate and chloride) and a chitosan derivative (methylpyroolidinone chitosan) was compared with three commercially available wound dressings made of collagen, calciumalginate, and gelatin, by evaluation in a fibroblast cell culture system. Three experimental models which reflect relevant stages of wound healing were used, and the significant influence of the experimental setting on the results was demonstrated. Collagen and methylpyrrolidinone chitosan were the most compatible materials under the investigated test conditions. Chitosan chloride and glutamate were the least compatible substances. The results indicated that wound dressings made of chitosan lactate and methylpyrrolidinone chitosan as well as the three commercially available dressings are well tolerated.     

Application of materials as medical devices with localized drug delivery capabilities for enhanced wound repair

The plentiful assortment of natural and synthetic materials can be leveraged to accommodate diverse wound types, as well as different stages of the healing process. An ideal material is envisioned to promote tissue repair with minimal inconvenience for patients. Traditional materials employed in the clinical setting often invoke secondary complications, such as infection, pain, foreign body reaction, and chronic inflammation. This review surveys the repertoire of surgical sutures, wound dressings, surgical glues, orthopedic fixation devices and bone fillers with drug eluting capabilities. It highlights the various techniques developed to effectively incorporate drugs into the selected material or blend of materials for both soft and hard tissue repair. The mechanical and chemical attributes of the resultant materials are also discussed, along with their biological outcomes in vitro and/or in vivo. Perspectives and challenges regarding future research endeavors are also delineated for next-generation wound repair materials.     

Antimicrobial and release study of drug loaded PVA/PEO/CMC wound dressings

The aim of the present study was to develop PVA/PEO/CMC/aloe vera (PPCAV) and PVA/PEO/CMC/curcumin (PPCCu) dressings with nonwoven polyester fabric as the support layer via freeze-drying (FD) approach. Tetracycline hydrochloride drug (TC) was loaded along with curcumin and aloe vera on these dressings. The morphology of the dressings was characterized by scanning electron microscopy. The swelling behavior, water vapor transmission rate (WVTR), in vitro drug release and antimicrobial nature were analyzed to assess the applicability of these freeze-dried membranes as wound dressing materials. The results show that these dressings made from PPCAVTC and PPCCuTC were highly porous with three-dimensional interconnected porous morphology. The cumulative release of drug from the dressings increases with increasing immersion time and continued up to 24 h, after that it gets leveled off. These dressings evidenced wonderful antimicrobial nature in vitro. These dressings were found to have more than 900 % PBS uptake, WVTR was found to be in the range 2,000–2,500 gm^?2 day^?1. These dressings possess many characteristics desirable in an ideal wound dressing material.     

In vitro investigations of a novel wound dressing concept based on biodegradable polyurethane

Non-healing and partially healing wounds are an important problem not only for the patient but also for the public health care system. Current treatment solutions are far from optimal regarding the chosen material properties as well as price and source. Biodegradable polyurethane (PUR) scaffolds have shown great promise for in vivo tissue engineering approaches, but accomplishment of the goal of scaffold degradation and new tissue formation developing in parallel has not been observed so far in skin wound repair. In this study, the mechanical properties and degradation behavior as well as the biocompatibility of a low-cost synthetic, pathogen-free, biocompatible and biodegradable extracellular matrix mimicking a PUR scaffold was evaluated in vitro. The novel PUR scaffolds were found to meet all the requirements for optimal scaffolds and wound dressings. These three-dimensional scaffolds are soft, highly porous, and form-stable and can be easily cut into any shape desired. All the material formulations investigated were found to be nontoxic. One formulation was able to be defined that supported both good fibroblast cell attachment and cell proliferation to colonize the scaffold. Tunable biodegradation velocity of the materials could be observed, and the results additionally indicated that calcium plays a crucial role in PUR degradation. Our results suggest that the PUR materials evaluated in this study are promising candidates for next-generation wound treatment systems and support the concept of using foam scaffolds for improved in vivo tissue engineering and regeneration.     

Silicone-coated non-woven polyester dressing enhances reepithelialisation in a sheep model of dermal wounds

Negative-pressure wound therapy (NPWT) also known as V.A.C.?(Vacuum-assisted closure), is widely used to manage various type of wounds and accelerate healing. NPWT has so far been delivered mainly via open-cell polyurethane (PU) foam or medical gauze. In this study an experimental setup of sheep wound model was used to evaluate, under NPWT conditions, the performance of a silicone-coated non-woven polyester (N-WPE) compared with PU foam and cotton hydrophilic gauze, used as reference materials. Animals were anesthetized with spontaneous breathing to create three 3?×?3?cm skin defects bilaterally; each animal received three different samples on each side (n?=?6 in each experimental group) and was subjected to negative and continuous 125?mmHg pressure up to 16?days. Wound conditions after 1, 8 and 16?days of treatment with the wound dressings were evaluated based on gross and histological appearances. Skin defects treated with the silicone-coated N-WPE showed a significant decrease in wound size, an increase of re-epithelialization, collagen deposition and wound neovascularisation, and a minimal stickiness to the wound tissue, in comparison with gauze and PU foam. Taken all together these findings indicate that the silicone-coated N-WPE dressing enhances wound healing since stimulates higher granulation tissue formation and causes minor tissue trauma during dressing changes.     

Silver-doped self-assembling di-phenylalanine hydrogels as wound dressing biomaterials

Chronic and acute wounds can be quickly contaminated and infected by microorganisms such as bacteria, multi-resistant organisms or fungi. The introduction of silver as anti-microbial agent into wound management has widely been demonstrated to be effective and contribute to wound healing. As a consequence, many approaches and different materials have been employed to synthesize antibacterial silver-hydrogels. In this work the introduction of silver particles into the fibrillar structure of self-assembling aromatic di-phenylalanine derivatives modified with aromatic groups such as 9-fluorenylmethoxycarbonyl is proposed to produce antibacterial wound dressings. Hydrogels doped with increasing amounts of silver were tested and adopted to modify flax textiles. The influence of silver on the structure of hydrogels was studied using light and confocal microscopy, while SEM–EDX allowed the characterization of the hydrogel coating on the surface of the textile substrates as well as the identification and distribution of silver nanoparticles. The antibacterial potential of the treated flax was demonstrated through microbiological tests on Staphylococcus aureus. The combination of the physico-chemical and anti-bacterial properties, together with the ease of preparation of these biomaterials, fulfils the requirement of clinically-effective wound dressings.     

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.     

体表创面修复材料的研究进展

创面修复材料对人体皮肤各种损伤的痊愈尤为重要,一直是临床研究的重要课题.介绍了3个发展阶段划分的新观点,即传统敷料、生物敷料及复合型敷料和组织工程化皮肤,并指出了各阶段存在的问题.其中组织工程原理为研究创面修复材料提供了广阔的前景,目前的研究工作多基于此理论,最后总结了今后的研发方向.     

Alginate membranes loaded with hyaluronic acid and silver nanoparticles to foster tissue healing and to control bacterial contamination of non-healing wounds

Chronic non-healing wounds are a clinically important problem in terms of number of patients and costs. Wound dressings such as hydrogels, hydrocolloids, polyurethane films and foams are commonly used to manage these wounds since they tend to maintain a moist environment which is shown to accelerate re-epithelialization. The use of antibacterial compounds is important in the management of wound infections. A novel wound-dressing material based on a blended matrix of the polysaccharides alginate, hyaluronic acid and Chitlac-silver nanoparticles is here proposed and its application for wound healing is examined. The manufacturing approach to obtain membranes is based on gelling, foaming and freeze-casting of alginate, hyaluronic acid and Chitlac-silver nanoparticles mixtures using calcium ions as the cross-linking agent. Comprehensive evaluations of the morphology, swelling kinetics, permeability, mechanical characteristics, cytotoxicity, capability to inhibit metalloproteinases and of antibacterial property were conducted. Biological in vitro studies demonstrated that hyaluronic acid released by the membrane is able to stimulate the wound healing meanwhile the metal silver exploits an efficient antibacterial activity against both planktonic bacteria and biofilms. Overall, the experimental data evidence that the studied material could be used as antibacterial wound dressing for wound healing promotion.

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Development of novel chitin/nanosilver composite scaffolds for wound dressing applications

Antibiotic resistance of microorganisms is one of the major problems faced in the field of wound care and management resulting in complications like infection and delayed wound healing. Currently a lot of research is focused on developing newer antimicrobials to treat wounds infected with antibiotic resistant microorganisms. Silver has been used as an antimicrobial agent for a long time in the form of metallic silver and silver sulfadiazine ointments. Recently silver nanoparticles have come up as a potent antimicrobial agent and are finding diverse medical applications ranging from silver based dressings to silver coated medical devices. Chitin is a natural biopolymer with properties like biocompatibility and biodegradability. It is widely used as a scaffold for tissue engineering applications. In this work, we developed and characterized novel chitin/nanosilver composite scaffolds for wound healing applications. The antibacterial, blood clotting and cytotoxicity of the prepared composite scaffolds were also studied. These chitin/nanosilver composite scaffolds were found to be bactericidal against S. aureus and E. coli and good blood clotting ability. These results suggested that these chitin/nanosilver composite scaffolds could be used for wound healing applications.     

Wound healing effect of silk fibroin/alginate-blended sponge in full thickness skin defect of rat

Silk fibroin (SF) and alginate (AA) have been proved to be invaluable natural materials in the field of biomedical engineering. This study was designed to compare the wound healing effect of SF, AA and SF/AA-blended sponge (SF/AA) with clinically used Nu Gauze^TM (CONT) in a rat full thickness wound model. Two circular skin wounds on the back of rat were covered with either of CONT, SF, AA or SF/AA. On the postoperative days of 3, 7, 10 and 14, residual wound area was calculated, and skin wound tissues were biopsied to measure the area of regenerated epithelium and collagen deposition as well as the number of proliferating cell nuclear antigen (PCNA)-immunoreactive cells. Half healing time (HT₅₀) of SF/AA was dramatically reduced as compared with that of SF, AA or CONT. Furthermore, SF/AA significantly increased the size of re-epithelialization and the number of PCNA positive cells, whereas the effect of SF/AA on collagen deposition was not significantly different as compared with that of SF or AA. These results demonstrate that the wound healing effect of SF/AA is the best among other treatments including SF and AA, and this synergic effect is mediated by re-epithelialization via rapid proliferation of epithelial cell.     

Fabrication of chitosan microparticles loaded in chitosan and poly(vinyl alcohol) scaffolds for tissue engineering application

In recent decades, the use of microparticle-mediated drug delivery is widely applied in the field of biomedical application. Here, we report the new dressing material with ciprofloxacin-loaded chitosan microparticle (CMP) impregnated in chitosan (CH) and poly(vinyl alcohol) (PVA) scaffold for effective delivery of drug in a sustained manner to the wound site. Moreover, the peculiar physiochemical and structural properties of the CH–CMP scaffold has proved better tensile strength and excellent swelling to achieve 82% of drug release. In vitro biocompatibility was done for both scaffold using NIH 3T3 fibroblasts and human keratinocytes (HaCaT) cell lines. In vitro fluorescent activity showed distinct biocompatibility with good cell adhesion and proliferation. However, the CH–CMP scaffold showed best result to act as promising biomaterial in effective drug delivery in tissue engineering.     

An All-in-One “4A Hydrogel”: through First-Aid Hemostatic,Antibacterial, Antioxidant,and Angiogenic to Promoting Infected Wound Healing

Currently used wound dressings are ineffective. Hence, there is a need to develop introduce a high-performance medicament with multiple functions including rapid hemostasis and excellent antibacterial activity to meet the growing worldwide demand for wound healing products. Here, inspired by the strong adhesion of mussels and the enzyme-mimicking activity of nanometallic biomaterials, the authors developed an injectable hydrogel to overcome multiple limitations of current wound dressings. The hydrogel is synthesized via esterification reaction between poly(vinyl alcohol) (PVA) and 3,4-dihydroxyphenylalanine (DOPA), followed by catechol-metal coordination between Cu²⁺ and the catechol groups of DOPA to form a PVA-DOPA-Cu (PDPC) hydrogel. The PDPC hydrogel possesses excellent tissue adhesive, antioxidative, photothermal, antibacterial, and hemostatic properties. The hydrogel rapidly and efficiently stopped bleeding under different traumatic conditions, including otherwise-lethal liver injury, high-pressure carotid artery rupture, and even fatal cardiac penetration injuries in animal models. Furthermore, it is demonstrated that the PDPC hydrogel affected high-performance wound repair and tissue regeneration by accelerating re-epithelialization, promoting collagen deposition, regulating inflammation, and contributing to vascularization. The results show that PDPC hydrogel is a promising candidate for rapid hemorrhage control and efficient wound healing in multiple clinical applications.