Composite Nanofibrous Scaffolds Research Articles

Tri-Layered Doxycycline-, Collagen- and Bupivacaine-Loaded Poly(lactic-co-glycolic acid) Nanofibrous Scaffolds for Tendon Rupture Repair.

Achilles tendon rupture is a severe injury, and its optimal therapy remains controversial. Tissue engineering scaffolds play a significant role in tendon healing and tissue regeneration. In this study, we developed tri-layered doxycycline/collagen/bupivacaine (DCB)-composite nanofibrous scaffolds to repair injured Achilles tendons. Doxycycline, collagen, and bupivacaine were integrated into poly(lactic-co-glycolic acid) (PLGA) nanofibrous membranes, layer by layer, using an electrospinning technique as healing promoters, a 3D scaffold, and painkillers, respectively. After spinning, the properties of the nanofibrous scaffolds were characterized. In vitro drug discharge behavior was also evaluated. Furthermore, the effectiveness of the DCB–PLGA-composite nanofibers in repairing ruptured Achilles tendons was investigated in an animal tendon model with histological analyses. The experimental results show that, compared to the pristine PLGA nanofibers, the biomolecule-loaded nanofibers exhibited smaller fiber size distribution and an enhanced hydrophilicity. The DCB-composite nanofibers provided a sustained release of doxycycline and bupivacaine for over 28 days in vivo. Additionally, Achilles tendons repaired using DCB-composite nanofibers exhibited a significantly higher maximum load-to-failure than normal tendons, suggesting that the biomolecule-incorporated nanofibers are promising scaffolds for repairing Achilles tendons.

Design and development of biomimetic electrospun sulphonated polyether ether ketone nanofibrous scaffold for bone tissue regeneration applications: in vitro and in vivo study

Bone defect restoration remains challenging in orthopedic medical practices. In this study an attempt is carried out to probe the use of new biomimetic SPEEK (sulfonated polyether ether ketone) based nanofibrous scaffold to deliver amine functionalized hydroxyapatite nanoparticles loaded resveratrol for its potent functionality in osteogenic differentiation. SPEEK polymer with reactive functional group SO3H was synthesized through process of sulphonation reaction. Amine functionalized nanoparticles with protonated amino groups revamp the molecular interaction by the formation of hydrogen bonds that in turn intensify the bioactivity of the nanofibrous scaffold. Osteoconductive functionalized nanohydroxyapatite enhances the cell proliferation and osteogenicity with improved cell attachment and spreading. The results of FT-IR, XRD, Carbon-Silica NMR and EDX analysis confirmed the amine functionalization of the hydroxyapatite nanoparticles. Surface morphological analysis of the fabricated nanofibers through SEM and AFM analysis shows vastly interconnected porous structure that mimics the bone extracellular matrix, which enhances the cell compatibility. Cell adhesion and live dead assay of the nanoscaffolds express less cytotoxicity. Mineralization and alkaline phosphatase assay establish the osteogenic differentiation of the nanofibrous scaffold. The in vitro biocompatibility studies reveal that the fabricated scaffold was osteo-compatible with MG63 cell lines. Hemocompatibility study further proved that the designed biomimetic nanofibrous scaffold was highly suitable for bone tissue engineering. The results of in vivo analysis in zebrafish model for the fabricated nanofibers demonstrated significant increase in the caudal fin regeneration indicating mineralization of osteoblast. Thus, the commending results obtained instigate the potentiality of the composite nanofibrous scaffold as an effective biomimetic substrate for bone tissue regeneration.

Fabrication and In Vitro Evaluation of A Chondroitin Sulphate-Polycaprolactone Composite Nanofibrous Scaffold for Potential Use in Dermal Tissue Engineering.

Objective Poly(ε-caprolactone) (PCL) has considerable mechanical and biological properties that make it a good candidate for tissue engineering applications. PCL alongside proteins and polysaccharides, like gelatin (GEL) and chondroitin sulphate (CS), can be used to fabricate composite scaffolds that provide mechanical and biological requirements for skin tissue engineering scaffolds. The aim of this study was fabricating novel composite nanofibrous scaffold containing various ratios of GEL/CS and PCL using co-electrospinning process. Materials and Methods In this experimental study, PCL mixed with a GEL/CS blend has limitations in miscibility and the lack of a common solvent. Here, we electrospun PCL and GEL/CS coincide separately on the same drum by using different nozzles to create composite nanofibrous scaffolds with different ratios (2:1, 1:1 and 1:2) of GEL to CS- PCL, and we mixed them at the micro/nanoscale. Morphology, porosity, phosphate-buffered saline (PBS) absorption, chemical structure, mechanical property and in vitro bioactivity of the prepared composite scaffolds were analysed. Results Scanning electron microscopy (SEM) images showed beadless nanofibres at all ratios of GEL to CS-PCL. The composite scaffolds (2:1, 1:1 and 1:2) had increased porosity compared to the PCL nanofibrous scaffolds, in addition to a significant increase in PBS absorption. The mechanical properties of the composite scaffolds were investigated under different conditions. The results demonstrated that all of the composite specimens had better strength when compared with the GEL/CS nanofibres. The increase in PCL ratio led to an increase in tensile strength of the nanofibres. Human dermal fibroblasts (HDF) were cultured on the fabricated composite scaffolds and evaluated by 3-(4,5-dimethylthiazol- 2-yl)-5-(3 carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) analysis and SEM. The results showed the bioactivity of these nanofibres and the potential for these scaffolds to be used for skin tissue engineering applications. ConclusionThe fabricated co-electrospun composite scaffolds had higher porosity and PBS absorption in comparison with the PCL nanofibrous scaffolds, in addition to significant improvements in mechanical properties under wet and dry conditions compared to the GEL/CS scaffold.

Poly (vinyl alcohol)/Silk Fibroin/Ag NPs composite nanofibers for bone tissue engineering.

In this work, electrospinning was used for the preparation of composite nanofibrous scaffold, of polyvinyl alcohol (PVA), silk fibroin (SF) extract of Bombyx mori cocoons and silver nanoparticles (Ag NPs), as a substrate for bone tissue engineering. The PVA pristine was prepared at a concentration of 10% wt. The composite nanofibers scaffolds of PVA was prepared with silk fibroin and silver nanoparticles, in relation of PVA: SF (90:10) (v/v) respectively. The formation and presence of AgNPs was confirmed by ultraviolet-visible spectroscopy (Uv-vis). The diameter distribution of the nanofibers was narrow by SEM using Image J software. The chemical composition was determined by FTIR spectra. The wettability was determined using water contact angle. The results showed the average nanofiber diameter of PVA10 pristine was 108.18 nm and to PVA10/SF/Ag NPs was 106.62 nm, no significant changes were noted in the mean diameter, but there were changes in its morphology. The average nanofiber diameter increase with the concentration of PVA at PVA15/SF/Ag NPs was 189.12 nm to PVA18/SF/Ag NPs was 224,23 nm. FTIR spectra indicated characteristic absorption peaks related to the chemical structure of PVA, fibroin and Ag NPs, it demonstrated good interactions between them, caused by strong intermolecular hydrogen bonds. The contact angle of the scaffolds PVA 10%wt decrease with the incorporation of fibroin and show hydrophilic characteristics. The achievements indicate the potential of the nanofibers of PVA15/SF/Ag NPs as a possible substitute for bone tissue engineering.Clinical Relevance-This establishes a possible substrate of PVA/SF/Ag NPs that exhibit desired properties such as porosity and high surface area to volume ratio for bone tissue engineering.

In vivo performance of electrospun tubular hyaluronic acid/collagen nanofibrous scaffolds for vascular reconstruction in the rabbit model

One of the main challenges of tissue-engineered vascular prostheses is restenosis due to intimal hyperplasia. The aim of this study is to develop a material for scaffolds able to support cell growth while tolerating physiological conditions and maintaining the patency of carotid artery model. Tubular hyaluronic acid (HA)-functionalized collagen nanofibrous composite scaffolds were prepared by sequential electrospinning method. The tubular composite scaffold has well-controlled biophysical and biochemical signals, providing a good matrix for the adhesion and proliferation of vascular endothelial cells (ECs), but resisting to platelets adhesion when exposed to blood. Carotid artery replacement experiment from 6-week rabbits showed that the HA/collagen nanofibrous composite scaffold grafts with endothelialization on the luminal surface could maintain vascular patency. At retrieval, the composite scaffold maintained good structural integrity and had comparable mechanical strength as the native artery. This study indicating that electrospun scaffolds combined with cells may become an alternative to prosthetic grafts for vascular reconstruction.Graphical

Efficacy of biocompatible trilayers nanofibrous scaffold with/without allogeneic adipose-derived stem cells on class II furcation defects of dogs' model.

This study aimed to evaluate the regenerative capacity of a newly-developed polycaprolactone (PCL)-based nanofibrous composite scaffold either alone or in combination with adipose-derived mesenchymal stem cells (ADSCs) as a treatment modality for class II furcation defects. After ADSCs isolation and scaffold characterization, the mandibular premolars of adult male mongrel dogs were selected and randomly assigned into three equal groups. In group I, class II furcation defects were surgically induced to the inter-radicular bone. While class II furcation defects of group II were induced as in group I. In addition, the defects were filled with the prefabricated scaffold. Moreover, class II furcation defects of group III were induced as in group II and instead the defects were filled with the prefabricated scaffold seeded with ADSCs. The dogs were sacrificed at 30days or at 60days. Periodontal wound healing/regeneration was evaluated by radiological examination using cone beam computed tomography and histologically using ordinary, histochemical, and immunohistochemical staining. In the two examination periods, group II defects compared to group I, and group III compared to the other groups showed a decrease in defect dimensions radiographically. Histologically, histochemically, and immunohistochemically, they significantly demonstrated better periodontal wound healing/regeneration, predominant collagen type I of newly formed bone and periodontal ligament with a significant increase in the immunoreactivity of vascular endothelial growth factor and osteopontin. The newly fabricated nanofibrous scaffold has enhanced periodontal wound healing/regeneration of class II furcation defects with further enhancement achieved when ADSCs seeded onto the scaffold before implantation. The implementation of our newly-developed PCL-based nanofibrous composite scaffolds in class II furcation defect either alone or in conjunction with ADSCs can be considered as a suitable treatment modality to allow periodontal tissues regeneration.

The Construction of Multi-Incorporated Polylactic Composite Nanofibrous Scaffold for the Potential Applications in Bone Tissue Regeneration.

To improve the bone regeneration ability of pure polymer, varieties of bioactive components were incorporated to a biomolecular scaffold with different structures. In this study, polysilsesquioxane (POSS), pearl powder and dexamethasone loaded porous carbon nanofibers (DEX@PCNFs) were incorporated into polylactic (PLA) nanofibrous scaffold via electrospinning for the application of bone tissue regeneration. The morphology observation showed that the nanofibers were well formed through electrospinning process. The mineralization test of incubation in simulated body fluid (SBF) revealed that POSS incorporated scaffold obtained faster hydroxyapatite depositing ability than pristine PLA nanofibers. Importantly, benefitting from the bioactive components of pearl powder like bone morphogenetic protein (BMP), bone mesenchymal stem cells (BMSCs) cultured on the composite scaffold presented higher proliferation rate. In addition, by further incorporating with DEX@PCNFs, the alkaline phosphatase (ALP) level and calcium deposition were a little higher based on pearl powder. Consequently, the novel POSS, pearl powder and DEX@PCNFs multi-incorporated PLA nanofibrous scaffold can provide better ability to enhance the biocompatibility and accelerate osteogenic differentiation of BMSCs, which has potential applications in bone tissue regeneration.

Biomimetic Polydopamine-Modified Silk Fibroin/Curcumin Nanofibrous Scaffolds for Chemo-photothermal Therapy of Bone Tumor.

The simultaneous therapy of tumor recurrence and bone defects resulting from surgical resection of osteosarcoma is still a challenge in the clinic. Combination therapy based on a localized drug-delivery system shows great promise in the treatment of osteosarcoma. Herein, bifunctional polydopamine (PDA)-modified curcumin (CM)-loaded silk fibroin (SF) composite (SF/CM-PDA) nanofibrous scaffolds, which combined photothermal therapy with chemotherapy to synergistically enhance osteosarcoma therapy, were prepared by PDA coating of the SF/CM nanofibrous scaffolds fabricated by supercritical carbon dioxide (SC-CO2) technology. The PDA coating improved hydrophilicity and mechanical strength of the SF/CM scaffolds. The SF/CM-PDA scaffolds present good photothermal conversion capacity and excellent photostability. The low pH and near-infrared (NIR) irradiation could effectively accelerate release of CM in the SF/CM-PDA scaffolds. The in vitro anticancer results indicated that the biocompatible SF/CM-PDA scaffolds had a long-term, stable, and superior anticancer effect compared to pure CM. Furthermore, the SF/CM-PDA scaffolds significantly increased the growth inhibition of osteosarcoma MG-63 cells under NIR irradiation (808 nm and 1.3 W/cm2). Besides, the SF/CM-PDA scaffolds could enhance osteoblast MC3T3-E1 cell proliferation in vitro when the mass ratio of CM was 0.05–0.5%. This work has therefore demonstrated that the bifunctional SF/CM-PDA scaffolds provide a competitive strategy for local osteosarcoma therapy and bone regeneration.

Metal-phenolic networks as a novel filler to advance multi-functional immunomodulatory biocomposites

Here, we exploited the potential applications of metal-phenolic networks (MPNs) as a novel type of filler for next-generation multi-functional immunomodulatory biocomposites. Tannic acid (TA) and Mg2+ were selected as the model phenolic ligand and metal ion, respectively, and used to assemble MPN particles, and a TA-Mg/polycaprolactone (PCL) composite nanofibrous scaffold was then prepared by blending electrospinning. Measurements of the resultant composite scaffold verified strong hydrogen-bonding interactions between TA motifs and PCL chains and the good dispersity of MPN particles throughout the substrate. Due to the pH-responsive disassembly kinetics of MPN complexes, both TA and Mg2+ displayed pH-responsive sustained release behaviour, thus eliciting significant biological effects. Specifically, TA and Mg2+ synergistically generated an anti-inflammatory micro-environment, which was beneficial for osteogenesis, and Mg2+ directly stimulated the osteogenic differentiation of stem cells. Consequently, the composite membrane significantly enhanced in vivo osteogenic performance when used as a barrier membrane to guide bone tissue regeneration. One unique advantage of this filler is that it combines the functions of both metal ions and phenolic ligands. By selecting different phenolic ligands and metal ions, a series of novel MPN-based fillers with unique functions could be easily obtained, suggesting that this system has a wide range of potential applications for next-generation multi-functional biocomposites.

Controlled release of resveratrol from a composite nanofibrous scaffold: Effect of resveratrol on antioxidant activity and osteogenic differentiation

Biocompatibility, mechanical strength, and osteogenesis properties of three-dimensional scaffolds are critical for bone tissue engineering. In addition, reactive oxygen species accumulate around bone defects and limit the activities of surrounding cells and bone formation. Therefore, the presence of an antioxidant in a bone tissue scaffold is also essential to address this issue. This study aimed to evaluate a composite nanofibrous scaffold similar to the natural extracellular matrix with antioxidant and osteogenic properties. To this end, polylactic acid (PLA)/organophilic montmorillonite (OMMT)/resveratrol (RSV) nanofibers were fabricated using the electrospinning method and characterized. RSV was used as an antioxidant, which promotes osteogenic differentiation, and OMMT was used as a mineral phase to increase the mechanical strength and control the release of RSV. The scaffolds' antioxidant activity was measured using DPPH assay and found 83.75% for PLA/OMMT/RSV nanofibers. The mechanical strength was increased by adding OMMT to the neat PLA. The biocompatibility of the scaffolds was investigated using an MTT assay, and the results did not show any toxic effects on human adipose mesenchymal stem cells (hASCs). Moreover, the Live/Dead assay indicated the appropriate distribution of live cells after 5 days. Cell culture results displayed that hASCs could adhere and spread on the surface of composite nanofibers. Meanwhile, the level of alkaline phosphatase, osteocalcin, and osteopontin was increased for hASCs cultured on the PLA/OMMT/RSV nanofibrous scaffold. Therefore, this study concludes that the RSV-loaded composite nanofibers with antioxidant and osteogenesis properties and appropriate mechanical strength can be introduced for bone tissue regeneration applications.

Polyacrylonitrile/Carbon Black nanoparticle/Nano-Hydroxyapatite (PAN/nCB/HA) composite nanofibrous matrix as a potential biomaterial scaffold for bone regenerative applications

The chemical resemblance of HA to natural bone has led to a widespread research approach to use synthetic HA as a bone substitute and replacement in biomedical application. Nanofibrous composites comprised of bioactive HA has been considered as a promising material for bone regeneration. However, the inadequate mechanical performance by HA agglomeration on nanofiber polymer matrix during electrospinning is a demanding challenge. In this study, we fabricated composite nanofibrous scaffold from the blends of PAN, nCB, and HA via electrospinning to observe the effect of nCB on the membrane properties. All the prepared samples were characterized by SEM-EDX, TEM, FTIR, XRD, TGA, water contact angle, swelling, and tensile strength test. Mineralized samples were also characterized by SEM-EDX, FTIR, XRD, and XPS. Incorporation of nCB reduced the average diameter of nanofibers without any significant changes in surface morphology in PAN/nCB scaffold. EDX spectra demonstrated an incremental increase in HA components with an increase in the amount of HA loading. TEM micrographs revealed dispersed nCB on the nanofibrous structure. Significant improvement in mechanical performance was observed in PAN/nCB/HA compared to PAN/HA scaffolds. Although an increase in the amount of HA in PAN/nCB/HA caused a reduction in the tensile strength and Young's modulus, the values were still greater than those without nCB. PAN/nCB/HA composite scaffold showed excellent mineralization of HA (Ca/P = 1.68) with platelet-like clustered protrusions (typical HA morphology) after incubation in SBF. MC3T3-E1 osteoblast cells showed excellent proliferation and adhesion on our prepared membranes. Our findings have demonstrated that nCB can strengthen the HA-based polymeric nanofibers and such biocompatible composites have strong potential to be used as bone and other hard tissue restoring materials.

Preparation and characterization of polyurethane/chitosan/CNT nanofibrous scaffold for cardiac tissue engineering

Myocardial infarction of cardiomyocytes is a leading cause of heart failure (HF) worldwide. Since heart has very limited regeneration capacity, cardiac tissue engineering (TE) to produce a bioactive scaffold is considered. In this study, a series of polyurethane solutions (5–7%wt) in aqueous acetic acid were prepared using electrospinning. A variety of Polyurethane (PU)/Chitosan (Cs)/carbon nanotubes (CNT) composite nanofibrous scaffolds with random and aligned orientation were fabricated to structurally mimic the extracellular matrix (ECM). Electrospun nanofibers were then characterized using field emission scanning electron microscopy (FESEM), transmission electron microscopy (TEM), X-ray diffraction (XRD), water contact angle, degradation studies, tensile tests, electrical resistance measurement and cell viability assay. The biocompatibility of electrospun random and aligned nanofibrous scaffolds with H9C2 Cells was confirmed. The results revealed that fabricated PU/Cs/CNT composite nanofibrous scaffolds were electro-conductive and aligned nanofibers could be considered as promising scaffolds with nano-scale features for regeneration of infarcted myocardium.

Different osteoconductivity of PLLA/PHB composite nanofibers prepared by one‐ and two‐nozzle electrospinning

AbstractElectrospinning is a method that has a high potential for use in tissue engineering due to its simplicity, cheapness, versatility, and high applicability for preparing of composite nanofibrous scaffolds. In this study, nanofibrous scaffolds were made of poly‐l‐lactic acid (PLLA) and Polyhydroxybutyrate (PHB) polymers by electrospinning single‐nozzle (combined polymers: C‐PLLA/PHB) and two‐nozzle (separated polymers: S‐PLLA/PHB). Constructed scaffolds were characterized using SEM, in vitro degradation, cell attachment, protein adsorption, and nontoxicity assays. Then, scaffolds osteoconductive capacity was investigated by culturing adipose‐derived stem cells (ADSCs) and by evaluating common osteogenic markers. Obtained results displayed that fibers diameter, scaffold degradation, and biocompatibility of S‐PLLA/PHB nanofibrous scaffold were increased compared to the C‐PLLA/PHB nanofibers. In addition, significantly increased alkaline phosphatase (ALP) activity, calcium content, and osteogenic‐related gene expression were also observed in the ADSCs cultured on S‐PLLA/PHB nanofibrous scaffold compared to the cultured cells on C‐PLLA/PHB nanofibrous scaffold. Overall, this study shows that using two‐nozzle electrospinning to constructing PLLA/PHB nanofibrous scaffold can improve its osteoconductive capacity, and also its combination with ADSCs can be a promising candidate to use in bone tissue engineering.

Nanofibrous ε-polycaprolactone scaffolds containing Ag-doped magnetite nanoparticles: Physicochemical characterization and biological testing for wound dressing applications in vitro and in vivo

Skin wounds can lead to numerous complications with dangerous health consequences. In this work, magnetite nanoparticles were doped with different concentrations of antimicrobial silver (Ag) ions and incorporated into the electrospun nanofibrous ε-polycaprolactone (PCL) scaffolds. Nanoparticles and scaffolds with various Ag contents were characterized using a range of physicochemical techniques. Ag entered magnetite as cations and preferentially positioned at tetrahedral sites, introducing lattice distortions and topographic irregularities. Amorphization of the structure due to accommodation of Ag expanded the lattice in the bulk and contracted it on the surface, where broadened distribution of Fe–O coordinations was detected. Promoting spin canting and diminishing the double exchange interaction through altered distribution of ferric and ferrous ions, Ag softened the magnetism of magnetite. By making the nanoparticle structure more defective, Ag modified the interface with the polymer and promoted the protrusion of the nanoparticles from the surface of the polymeric nanofibers, thus increasing their roughness and hydrophilicity, with positive repercussions on cell adhesion and growth. Both the viability of human melanocytes and the antibacterial activity against E. coli and S. aureus increased with the concentration of Ag in the magnetite phase of the scaffolds. Skin wound healing rate in rats also increased in direct proportion with the concentration of Ag in the magnetite phase, and no abnormalities in the dermal and epidermal tissues were visible on day 10 in the treatment group. These results imply an excellent potential of these composite nanofibrous scaffolds for use as wound dressings and in other reconstructive skin therapies.

Paclitaxel-loaded lignin particle encapsulated into electrospun PVA/PVP composite nanofiber for effective cervical cancer cell inhibition

Electrospun composite nanofibrous scaffolds have been regarded as a potential carrier for local drug delivery to prevent tumor recurrence. Herein, a model drug (paclitaxel) was creatively loaded into lignin nanoparticles (PLNPs) and then encapsulated into the polymer of poly (vinyl alcohol)/polyvinyl pyrrolidone which has been fabricated into a composite nanofibrous membrane (PVA/PVP-PLNPs) for use as a drug carrier using the electrospinning technique. The fabricated PVA/PVP-PLNPs membranes exhibited good particle distribution, mechanical properties, thermal stability and biocompatibility. In vitro experiments showed that combining lignin nanoparticles by electrospinning not only improved the drug release profile, but also enhanced the hydrophilicity of nanofibrous membranes which was beneficial to cell adhesion and proliferation. Cellular experiments demonstrated that PVA/PVP-2%PLNPs membrane showed good cell inhibition ability, and the cell survival rate was only 21% at day 7. It indicates that the as-prepared PVA/PVP-PLNPs composite nanofibers are promising candidates for local anticancer therapy.

Preparation and characterization of aspirin-loaded polylactic acid/graphene oxide biomimetic nanofibrous scaffolds

The combination of biomimetic scaffolds and nano drug delivery has been proposed to be an effective solution to the inherent limitations of the former in regulating cell behavior and bone tissue regeneration. Herein, a series of three-dimensional (3D) aspirin-loaded polylactic acid/graphene oxide (PLA/GO) porous biomimetic nanofibrous composite scaffolds (PBNCSs) was successfully prepared by phase separation. Results showed that the PLA/GO scaffolds have a biomimetic nanofibrous porous structure and a thin GO film covering the PLA nanofibers, which endows the latter with significantly improved hydrophilicity. Close interactions were noted in the GO–PLA interface. GO reduced the mechanical properties of the composite scaffolds but increased their thermal stability. The water absorption rate increased from 12.5% to 206.81% as the GO content increased from 0 to 5%. Addition of GO improved the deposition rate and amount of hydroxyapatite on the scaffolds. Overall, the PLA/GO PBNCSs demonstrated good cytocompatibility and sustained-release performance.

Accelerated diabetic wound healing by topical application of combination oral antidiabetic agents-loaded nanofibrous scaffolds: An in vitro and in vivo evaluation study

The combination of oral antidiabetic drugs, pioglitazone, metformin, and glibenclamide, which also exhibit the strongest anti-inflammatory action among oral antidiabetic drugs, were loaded into chitosan/gelatin/polycaprolactone (PCL) by electrospinning and polyvinyl pyrrolidone (PVP)/PCL composite nanofibrous scaffolds by pressurized gyration to compare the diabetic wound healing effect. The combination therapies significantly accelerated diabetic wound healing in type-1 diabetic rats and organized densely packed collagen fibers in the dermis, it also showed better regeneration of the dermis and epidermis than single drug-loaded scaffolds with less inflammatory cell infiltration and edema. The formation of the hair follicles started in 14 days only in the combination therapy and lower proinflammatory cytokine levels were observed compared to single drug-loaded treatment groups. The combination therapy increased the wettability and hydrophilicity of scaffolds, demonstrated sustained drug release over 14 days, has high tensile strength and suitable cytocompatibility on L929 (mouse fibroblast) cell and created a suitable area for the proliferation of fibroblast cells. Consequently, the application of metformin and pioglitazone-loaded chitosan/gelatin/PCL nanofibrous scaffolds to a diabetic wound area offer high bioavailability, fewer systemic side effects, and reduced frequency of dosage and amount of drug.

Acceleration of osteogenic differentiation by sustained release of BMP2 in PLLA/graphene oxide nanofibrous scaffold

After about three decades of experience, tissue engineering has become one of the most important approaches in reconstructive medical research to treat non‐self‐healing bone injuries and lesions. Herein, nanofibrous composite scaffolds fabricated by electrospinning, which containing of poly(L‐lactic acid) (PLLA), graphene oxide (GO), and bone morphogenetic protein 2 (BMP2) for bone tissue engineering applications. After structural evaluations, adipose tissue derived mesenchymal stem cells (AT‐MSCs) were applied to monitor scaffold's biological behavior and osteoinductivity properties. All fabricated scaffolds had nanofibrous structure with interconnected pores, bead free, and well mechanical properties. But the best biological behavior including cell attachment, protein adsorption, and support cells proliferation was detected by PLLA‐GO‐BMP2 nanofibrous scaffold compared to the PLLA and PLLA‐GO. Moreover, detected ALP activity, calcium content and expression level of bone‐related gene markers in AT‐MSCs grown on PLLA‐GO‐BMP2 nanofibrous scaffold was also significantly promoted in compression with the cells grown on other scaffolds. In fact, the simultaneous presence of two factors, GO and BMP2, in the PLLA nanofibrous scaffold structure has a synergistic effect and therefore has a promising potential for tissue engineering applications in the repair of bone lesions.

Preparation and characterization of a novel polylactic acid/hydroxyapatite composite scaffold with biomimetic micro-nanofibrous porous structure.

Combining synthetic polymer scaffolds with inorganic bioactive factors is widely used to promote the bioactivity and bone conductivity of bone tissue. However, except for the chemical composition of scaffold, the biomimetic structure also plays an important role in its application. In this study, we report the fabrication of polylactic acid/hydroxyapatite (PLA/HA) composite nanofibrous scaffolds via phase separation method to mimic the native extracellular matrix (ECM). The SEM analysis showed that the addition of HA dramatically impacted the morphology of the PLA matrix, which changed from 3D nanofibrous network structure to a disorderly micro-nanofibrous porous structure. At the same time, HA particles could be evenly dispersed at the end of the fiber. The FTIR and XRD demonstrated that there was not any chemical interaction between PLA and HA. Thermal analyses showed that HA could decrease the crystallization of PLA, but improve the thermal decomposition temperature of the composite scaffold. Moreover, water contact angle analysis of the PLA/HA composite scaffold demonstrated that the hydrophilicity increased with the addition of HA. Furthermore, apatite-formation ability tests confirmed that HA could not only more and faster induced the deposition of weak hydroxyapatite but also induced specific morphology of HA.

Chondroinductive impact of polyethersulfone/benzyl hyaluronate nanofibrous scaffold on human mesenchymal stem cells

Over the years, considerable improvements have been made for the repair of cartilage lesions in the field of cartilage tissue engineering. Constructing scaffolds with close similarity to niches regarding biochemical composition and mechanical characteristics with the best efficiency is a great challenge for scientists and researchers in this field. On the other hand, natural polymers such as hyaluronic acid are difficult to be used in scaffolds construction due to some problems arising from their physicochemical properties such as poor mechanical strength. In this study, to overcome this problem a new nanofibrous composite scaffold was constructed using one of the derivatives of hyaluronic acid, benzyl hyaluronate (BH), in combination with Polyethersulfone (PES) and its chondroinductivity potential was measured using human adipose derived mesenchymal stem cells (hADSCs). Scanning electron microscopy (SEM) and tensile tests were performed to evaluate the characteristics of the composite scaffolds. Common chondrogenic markers (SOX9, Col II and Aggrecan) were assessed by Real‐time PCR. Alcian blue staining was performed as well to test possible glycosaminoglycans (GAGs) production. Expressions of mentioned genes and positive staining of GAGs even in those BH/PES groups which were not treated with chondrogenic differentiation medium confirmed the chondro‐inductive potential of composite PES/BH scaffolds. Although BH has an accepted effect on induction of cartilage, incorporating BH with another polymer such as PES and enhancing the mechanical properties, and thus easier handling of the scaffold can be an effective step in making niche‐like scaffolds.