Graphene oxide-encapsulated baghdadite nanocomposite improved physical, mechanical, and biological properties of a vancomycin-loaded PMMA bone cement.

Polymethyl methacrylate (PMMA) bone cement is commonly used in orthopedic surgeries to fill the bone defects or fix the prostheses. These cements are usually containing amounts of a nonbioactive radiopacifying agent such as barium sulfate and zirconium dioxide, which does not have a good interface compatibility with PMMA, and the clumps formed from these materials can scratch metal counterfaces. In this work, graphene oxide encapsulated baghdadite (GOBgh) nanoparticles were applied as radiopacifying and bioactive agent in a PMMA bone cement containing 2 wt.% of vancomycin (VAN). The addition of 20 wt.% of GOBgh (GOBgh20) nanoparticles to PMMA powder caused a 33.6% increase in compressive strength and a 70.9% increase in elastic modulus compared to the Simplex® P bone cement, and also enhanced the setting properties, radiopacity, antibacterial activity, and the apatite formation in simulated body fluid. In vitro cell assessments confirmed the increase in adhesion and proliferation of MG-63 cells as well as the osteogenic differentiation of human adipose-derived mesenchymal stem cells on the surface of PMMA-GOBgh20 cement. The chorioallantoic membrane assay revealed the excellent angiogenesis activity of nanocomposite cement samples. In vivo experiments on a rat model also demonstrated the mineralization and bone integration of PMMA-GOBgh20 cement within four weeks. Based on the promising results obtained, PMMA-GOBgh20 bone cement is suggested as an optimal sample for use in orthopedic surgeries.

Core-shell nanofibers containing L-arginine stimulates angiogenesis and full thickness dermal wound repair.

Despite the advances in medicine, wound healing is still challenging and piques the interest of biomedical engineers to design effective wound dressings using natural and artificial polymers. In present study, coaxial electrospinning was employed to fabricate core-shell nanofiber-based wound dressing, with core composed of polyacrylamide (PAAm) and shell comprising 0.5 % solution of L-Arginine (L-Arg) in aloe vera and keratin (AloKr). Aloe vera and keratin were added as natural polymers to promote angiogenesis, reduce inflammation, and provide antibacterial activity, whereas PAAm in core was used to improve the tensile properties of the wound dressing. Moreover, L-Arg was incorporated in shell to promote angiogenesis and collagen synthesis. The fiber diameter of PAAm/(AloKr/L-Arg) core-shell fibers was (93.33 ± 35.11 nm) with finer and straighter fibers and higher water holding capacity due to increased surface area to volume ratio. In terms of tensile properties, the PAAm/(AloKr/L-Arg) core-shell nanofibers with tensile strength and elastic modulus of 2.84 ± 0.27 MPa and 62.15 ± 5.32 MPa, respectively, showed the best mechanical performance compared to other nanofibers tested. Furthermore, PAAm/(AloKr/L-Arg) exhibited the highest L-Arg release (87.62 ± 3.02 %) and viability of L929 cells in vitro compared to other groups. In addition, the highest rate of in vivo full thickness wound healing was observed in PAAm/(AloKr/L-Arg) group compared to other groups. It significantly enhanced the angiogenesis, neovascularization, and cell proliferation. The prepared PAAm/(AloKr/L-Arg) core-shell nanofibrous dressing could be promising for full-thickness wound healing.

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.

Coaxial electrospun angiogenic nanofiber wound dressing containing advanced platelet rich-fibrin.

Advanced platelet-rich fibrin (A-PRF) provides long-term release of growth factors that potentially accelerate wound healing. In this study, core-shell nanofibrous structure of polyvinyl alcohol (PVA) core and gelatin (Gel) shell containing A-PRF is fabricated through coaxial electrospinning method. PVA/(Gel/A-PRF) core-shell nanofibers had the highest porosity, specific surface area and hydrophilicity among all the studied nanofibers. PVA/(Gel/A-PRF) core-shell nanofibers with a tensile stress of 7.43 ± 0.38 MPa and an elastic modulus of 102.05 ± 9.36 MPa had higher mechanical properties than PVA/Gel/A-PRF and PVA/Gel blend nanofibers. PVA/(Gel/A-PRF) nanofibers had a 47.41 ± 1.97 % degradability over 7 days of immersion in PBS. The release of VEGF and PDGF-AB growth factors from PVA/(Gel/A-PRF) core-shell nanofibers and PVA/Gel/A-PRF blend nanofibers were evaluated. It was shown that L929 cell proliferation and adhesion on PVA/(Gel/A-PRF) core-shell nanofibers were significantly higher than other samples. Also, chicken chorioallantoic membrane (CAM) assay revealed that the highest angiogenic potential among the studied samples related to PVA/(Gel/A-PRF) sample. In vivo studies on a rat model showed wound closure for PVA/(Gel/A-PRF) group was 97.83 ± 2.03 % after 11 days. Histopathological and immunohistochemical examinations approved the acceleration of wound healing by PVA/(Gel/A-PRF) core-shell nanofiber dressing. The results strongly recommend the use of PVA/(Gel/A-PRF) core-shell nanofiber dressing for the repair of full-thickness wounds.

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.

Platelet rich fibrin containing nanofibrous dressing for wound healing application: Fabrication, characterization and biological evaluations.

Recently, nanofibrous structures have shown great potential for a wide range of medical applications. The aim of the current study was to evaluate the wound healing process using Polycaprolactone/Keratin/Platelet-rich fibrin (PCL/Kr/PRF) fibrous scaffold fabricated through electrospinning process. A range of techniques were utilized to fully characterize the chemical, physical and biological properties of the resultant structure. Results revealed that by the addition of only 0.5%w/v PRF to PCL/Kr (PCL/Kr/0.5PRF) sample, the fibers diameter decreased from 193.93 ± 64.80 nm to 65.98 ± 14.03 nm, and the stress at break demonstrated a 18.27% increase in comparison to the PCL sample (from 2.90 ± 0.80 MPa to 3.43 ± 0.90 MPa). The PCL/Kr/0.5PRF scaffold showed more antibacterial activity against gram-positive and gram-negative bacteria than PCL/Kr sample. Based on enzyme-linked immunosorbent assays, the PCL/Kr/0.5PRF sample revealed an independent release of VEGF and PDGF for 7 days. Cell viability studies demonstrated non-cytotoxic nature of PRF-containing dressings. Also, chorioallantoic membrane (CAM) assay was performed to evaluate the angiogenic potential of the wound dressings. The in vivo assessments also showed that PCL/Kr/0.5PRF accelerated the wound healing process in terms of collagen deposition and the formation of skin appendages which was comparable to the normal skin. Overall, the data presented in this study greatly suggest that the PCL/Kr/0.5PRF wound dressing could be a suitable candidate for wound healing and skin regeneration.