Keratin- and VEGF-Incorporated Honey-Based Sponge-Nanofiber Dressing: An Ideal Construct for Wound Healing.

To overcome the drawbacks of single-layered wound dressings, bilayer dressings are now introduced as an alternative to achieve effective and long-term treatment. Here, a bilayer dressing composed of electrospun nanofibers in the bottom layer (BL) and a sponge structure as the top layer (TL) is presented. Hydrophilic poly(acrylic acid) (PAAc)-honey (Hny) with interconnected pores of 76.04 µm was prepared as the TL and keratin (Kr), Hny, and vascular endothelial growth factor (VEGF) were prepared as the BL. VEGF indicates a gradual release over 7 days, promoting angiogenesis, as proven by the chick chorioallantoic membrane assay and in vivo tissue histomorphology observation. Additionally, the fabricated dressing material indicated a satisfactory tensile profile, cytocompatibility for human keratinocyte cells, and the ability to promote cell attachment and migration. The in vivo animal model demonstrated that the full-thickness wound healed faster when it was covered with PAAc-Hny/Hny-Kr-VEGF than in other groups. Additionally, faster blood vessel formation, collagen synthetization, and epidermal layer generation were also confirmed, which have proven efficient healing acceleration in wounds treated with synthesized bilayer dressings. Our findings indicated that the fabricated material can be promising as a functional wound dressing.

Asymmetric tri-layer sponge-nanofiber wound dressing containing insulin-like growth factor-1 and multi-walled carbon nanotubes for acceleration of full-thickness wound healing.

To more closely resemble the structure of natural skin, multi-layered wound dressings have been developed. Herein, a tri-layer wound dressing was prepared containing a polyacrylamide (PAAm)-Aloe vera (Alo) sponge that had been incorporated with insulin-like growth factor-1 (IGF1) to provide a porous absorbent layer, which was able to promote angiogenesis. Alo nanofibers with multi-walled carbon nanotubes (MWCNT) were electrospun into the bottom layer to increase cell behavior, and a small film of stearic acid was put as a top layer to avoid germy penetration. In comparison to bilayer dressing, the tensile strength increased by 17.0 % (from 0.200 ± 0.010 MPa to 0.234 ± 0.022 MPa) and the elastic modulus by 45.6 % (from 0.217 ± 0.003 MPa to 0.316 ± 0.012 MPa) in the presence of Alo nanofibers containing 0.5 wt% of MWCNT at the bottom layer of Trilayer0.5 dressing. The release profile of IGF1, the antibacterial activity and the degradability of different wound dressings were investigated. Trilayer0.5 indicated the highest cell viability, cell adhesion and angiogenic potential among the prepared dressing materials. In-vivo rat model revealed that the Trilayer0.5 dressing treated group had the highest rate of wound closure and wound healing within 10 days compared to other groups.

A 3D printed polylactic acid-Baghdadite nanocomposite scaffold coated with microporous chitosan-VEGF for bone regeneration applications.

Three-dimensional (3D) printing technology has become an advanced approach for fabricating patient-specific scaffolds with complex geometric shapes to replace damaged or diseased tissue. Herein, polylactic acid (PLA)-Baghdadite (Bgh) scaffold were made through the fused deposition modeling (FDM) 3D printing method and subjected to alkaline treatment. Following fabrication, the scaffolds were coated with either chitosan (Cs)-vascular endothelial growth factor (VEGF) or lyophilized Cs-VEGF known as PLA-Bgh/Cs-VEGF and PLA-Bgh/L.(Cs-VEGF), respectively. Based on the results, it was found that the coated scaffolds had higher porosity, compressive strength and elastic modulus than PLA and PLA-Bgh samples. Also, the osteogenic differentiation potential of scaffolds following culture with rat bone marrow-derived mesenchymal stem cells (rMSCs) was evaluated through crystal violet and Alizarin-red staining, alkaline phosphatase (ALP) activity and calcium content assays, osteocalcin measurements, and gene expression analysis. The release of VEGF from the coated scaffolds was assessed and also the angiogenic potential of scaffolds was evaluated. The sum of results presented in the current study strongly suggests that the PLA-Bgh/L.(Cs-VEGF) scaffold can be a proper candidate for bone healing applications.

PDGF and VEGF-releasing bi-layer wound dressing made of sodium tripolyphosphate crosslinked gelatin-sponge layer and a carrageenan nanofiber layer.

The use of dressings is one of the most common methods for wound treatment. Since most single-layer dressings cannot mimic the hierarchical structure of the skin well, multi-layer dressings have been considered. In this study, a bilayer dressing was fabricated using a gelatin sponge layer cross-linked with sodium tripolyphosphate (Gel-STPP) and a layer of carrageenan nanofibers containing platelet-rich fibrin (Carr-PRF). Chemical interactions between the two layers were characterized by FTIR, and the microstructure was visualized by SEM. It was found that the presence of Carr-PRF nanofiber layer increased tensile strength by 12.96 % (from 0.216 ± 0.015 to 0.268 ± 0.036 MPa) and elastic modulus by 56.70 % (from 0.388 ± 0.072 to 0.608 ± 0.029 MPa) compared to Gel-STPP sponge. Gel-STPP/Carr-PRF wound dressing had a 45.76 ± 4.18 % degradability after 7 days of immersion in phosphate buffered saline (PBS). PRF-containing bilayer wound dressing was able to sustainably release growth factors over 7 days. The Carr-PRF nanofiber layer coated on Gel-STPP sponge was an ideal environment for adhesion and proliferation of L929 cells. Gel-STPP/Carr-PRF bilayer dressing outperformed the other tested samples in terms of angiogenic potential. Average wound closure was 94.21 ± 2.06 % in Gel-STPP/Carr-PRF dressing treated rats after 14 days, and based on the histopathological and immunohistochemical examinations, the Gel-STPP/Carr-PRF dressing group augmented full-thickness wound healing, keratin layer and skin appendages formation after 14 days.

Dual drug delivery system based on layered double hydroxides/carboxymethyl cellulose-poly ethylene oxide bionanocomposite electrospun fibrous mats: Fabrication, characterization, in-vitro and in-vivo studies.

The main goal of the present project was to design and develop ibuprofen (IBU) and layered double hydroxides-vancomycin (LDH-VAN) nanohybrid loaded bionanocomposite fibrous mats to increase the wound healing rate. Thus, first, LDH-VAN nanohybrid particles was synthesized by in-situ incorporation of VAN into the Mg-Al-LDH interlayers during the co-precipitation of hydroxides. Then, LDH-VAN/IBU/CMC-PEO bionanocomposite fibrous mats were fabricated by electrospinning technique. Test samples were examined XRD, SEM, TEM, TGA, and FTIR. In vitro drug release test was performed in the phosphate buffer solution (pH = 7.4) to prove the efficiency of the fabricated bionanocomposite fibrous mats as a sustained-release carrier for both VAN and IBU. All the fabricated bionanocomposite fibrous mats did not displayed any significant cytotoxicity on NIH/3 T3 fibroblast cells. The wound area in the rats treated with LDH-VAN/IBU/CMC-PEO bionanocomposite fibrous mats was less than other treatment groups. Based on histological analysis, the LDH-VAN/IBU/CMC-PEO bionanocomposite fibrous mats possess a faster wound healing than other nanofibrous mats. Data obtained from the present project indicated that LDH-VAN/IBU/CMC-PEO bionanocomposite fibrous mats could accelerate the wound healing process.

Comparison of physical, mechanical and biological effects of leucocyte-PRF and advanced-PRF on polyacrylamide nanofiber wound dressings: In vitro and in vivo evaluations.

Platelet-rich fibrin (PRF) is extracted from the blood without biochemical interference and, also, with the ability of a long-term release of growth factors that can stimulate tissue repair and regerenation. Here, leucocyte- and platelet-rich fibrin (L-PRF) and advanced platelet-rich fibrin (A-PRF) were extracted and utilized for the creation of nanofibers containing polyacrylamide (PAAm), PAAm / L-PRF and PAAm / A-PRP through electrospinning processing technique. The effect of the type of PRF on the physical, mechanical and biological properties of the resultant nanofiberous wound dressings are thoroughly evaluated. The results presented in the current study reveals that the fiber diameter is grealtly reduced through the utilization of L-PRF. In addition, mechanical property is also positively affected by L-PRF and the degradation rate is found to be higher compared to A-PRF group. The L929 cells proliferation and adhesion, angiogenesis potential and wound healing ability was significantly higher in PAAm/A-PRF nanofibers compared to pure PAAm and PAAm/L-PRF nanofibers owed to the release of vascular endothelial growth factor (VEGF) and platelet derived growth factor (PDGF). Overall, the utilization of L-PRF or A-PRF can improve the physical, mechanical and biological behavior of nanofiber making them an ideal candidate for wound dressings, with the emphasis on the skin tissue repair and regeneration applications.

Preparation of a biomimetic bi-layer chitosan wound dressing composed of A-PRF/sponge layer and L-arginine/nanofiber.

To better mimic the structure of skin tissue, the use of a multi-layered wound dressing has been proposed. In the present study, a sponge-nanofibrous bi-layer dressing is designed. For this purpose, a chitosan/polyethylene glycol (CsPEG) sponge with advanced platelet-rich fibrin (A-PRF) was prepared as the upper layer of wound dressing, and a Cs/L-arginine electrospun nanofiber layer as the bottom layer. After physical, chemical and mechanical evaluations, the release of platelet-derived growth factor-AB (PDGF-AB), vascular endothelial growth factor (VEGF) and L-arginine were investigated. The antibacterial activity, cell viability and attachment of Bi-layer1.5 dressing (CsPEG/1.5A-PRF sponge coated with Cs/0.5 L-arginine nanofibers) were significantly higher than other dressings. Also, Bi-layer1.5 dressing increased the angiogenic potential and accelerated the wound healing, compared to other samples. Given the promising obtained results, the use of Bi-layer1.5 wound dressing with the ability to release growth factors and L-arginine is highly recommended to treat full-thickness wounds.

Emerging treatment strategies in wound care.

Wound healing is a complex process in tissue regeneration through which the body responds to the dissipated cells as a result of any kind of severe injury. Diabetic and non-healing wounds are considered an unmet clinical need. Currently, different strategic approaches are widely used in the treatment of acute and chronic wounds which include, but are not limited to, tissue transplantation, cell therapy and wound dressings, and the use of an instrument. A large number of literatures have been published on this topic; however, the most effective clinical treatment remains a challenge. The wound dressing involves the use of a scaffold, usually using biomaterials for the delivery of medication, autologous stem cells, or growth factors from the blood. Antibacterial and anti-inflammatory drugs are also used to stop the infection as well as accelerate wound healing. With an increase in the ageing population leading to diabetes and associated cutaneous wounds, there is a great need to improve the current treatment strategies. This research critically reviews the current advancement in the therapeutic and clinical approaches for wound healing and tissue regeneration. The results of recent clinical trials suggest that the use of modern dressings and skin substitutes is the easiest, most accessible, and most cost-effective way to treat chronic wounds with advances in materials science such as graphene as 3D scaffold and biomolecules hold significant promise. The annual market value for successful wound treatment exceeds over $50 billion US dollars, and this will encourage industries as well as academics to investigate the application of emerging smart materials for modern dressings and skin substitutes for wound therapy.

Fabrication and evaluation of Cs/PVP sponge containing platelet-rich fibrin as a wound healing accelerator: An in vitro and in vivo study.

Despite significant advances in surgery and postoperative care, there are still challenges in the treatment of wounds. In the current study, a freeze-dried chitosan (Cs)/polyvinylpyrrolidone (PVP) sponges containing platelet-rich fibrin (PRF at 1, 1.5 and 2% w/v) for wound dressing application is fabricated and fully characterized. Addition of 1% w/v of PRF to Cs/PVP (CS/PVP/1PRF) sample significantly increased the tensile strength (from 0.147 ± 0.005 to 0.242 ± 0.001 MPa), elastic modulus (from 0.414 ± 0.014 to 0.611 ± 0.022 MPa) and strain at break (from 53.4 ± 0.9 to 61.83 ± 1.17%) compared to Cs sample, and was hence selected as the optimal sample. The antibacterial activity of Cs/PVP/1PRF sponge wound dressing against E. coli and S. aureus was confirmed to be effective. Enzyme-linked immunosorbent assays revealed that the release of both VEGF and PDGF-AB from PRF powder, as well as PDGF-AB from Cs/PVP/1PRF sample was time-independent, but the release of VEGF from Cs/PVP/1PRF sample increased significantly with time. According to MTT and CAM assays, the Cs/PVP/1PRF sample significantly increased proliferation and angiogenic potential, respectively. Furthermore, in vivo studies demonstrated a 97.16 ± 1.55% wound closure for Cs/PVP/1PRF group after 14 days.

Development of a T Cell-targeted siRNA Delivery System Against HIV-1 Using Modified Superparamagnetic Iron Oxide Nanoparticles: An In Vitro Study.

In spite of the promising properties of small interfering RNAs (siRNAs) in the treatment of infectious diseases, safe and efficient siRNA delivery to target cells is still a challenge. In this research, an effective siRNA delivery approach (against HIV-1) has been reported using targeted modified superparamagnetic iron oxide nanoparticles (SPIONs). Trimethyl chitosan-coated SPION (TMC-SPION) containing siRNA was synthesized and chemically conjugated to a CD4-specific monoclonal antibody (as a targeting moiety). The prepared nanoparticles exhibited a high siRNA loading efficiency with a diameter of about 85 nm and a zeta potential of +28 mV. The results of the cell viability assay revealed the low cytotoxicity of the optimized nanoparticles. The cellular delivery of the targeted nanoparticles (into T cells) and the gene silencing efficiency of the nanoparticles (containing anti-nef siRNA) were dramatically improved compared to those of nontargeted nanoparticles. In conclusion, this study offers a promising targeted delivery platform to induce gene silencing in target cells. Our approach may find potential use in the design of effective vehicles for many therapeutic applications, particularly for HIV treatment.

Polymethyl Methacrylate-Based Bone Cements Containing Carbon Nanotubes and Graphene Oxide: An Overview of Physical, Mechanical, and Biological Properties.

Every year, millions of people in the world get bone diseases and need orthopedic surgery as one of the most important treatments. Owing to their superior properties, such as acceptable biocompatibility and providing great primary bone fixation with the implant, polymethyl methacrylate (PMMA)-based bone cements (BCs) are among the essential materials as fixation implants in different orthopedic and trauma surgeries. On the other hand, these BCs have some disadvantages, including Lack of bone formation and bioactivity, and low mechanical properties, which can lead to bone cement (BC) failure. Hence, plenty of studies have been concentrating on eliminating BC failures by using different kinds of ceramics and polymers for reinforcement and also by producing composite materials. This review article aims to evaluate mechanical properties, self-setting characteristics, biocompatibility, and bioactivity of the PMMA-based BCs composites containing carbon nanotubes (CNTs), graphene oxide (GO), and carbon-based compounds. In the present study, we compared the effects of CNTs and GO as reinforcement agents in the PMMA-based BCs. Upcoming study on the PMMA-based BCs should concentrate on trialing combinations of these carbon-based reinforcing agents as this might improve beneficial characteristics.

Incorporation of chitosan/graphene oxide nanocomposite in to the PMMA bone cement: Physical, mechanical and biological evaluation.

One of the most popular types of bone cements is polymethylmethacrylate (PMMA). The properties of this bone cement have attracted many researchers effort to modify its properties. In this study, after preparation of chitosan (Cs) powder and Cs/graphene oxide (GO) nanocomposite powder, they were added homogeneously to the PMMA bone cement with different percentages. The results showed that the addition of 25 wt% of Cs/GO nanocomposite powder to the PMMA bone cement cause to increase the compressive strength by 16.2%, the compressive modulus by 69.1% and the bending strength by 24.0%. The obtained results showed that by adding Cs/GO nanocomposite powder to the PMMA bone cement, setting time and injectability were increased, maximum temperature was decreased and apatite-like deposition was increased after 4 weeks of incubation in SBF solution. The results of MG-63 cell culture confirmed the improvement of cell viability, growth and cell adhesion for 25 wt% PMMA-Cs/GO composite bone cement. Therefore, it can be concluded that 25 wt% PMMA-Cs/GO composite bone cement with improved mechanical, physical and biological properties can be a good replacement for common commercial bone cements in orthopedic applications.