Development of polyvinyl alcohol nanofiber scaffolds loaded with flaxseed extract for bone regeneration: phytochemicals, cell proliferation, adhesion, and osteogenic gene expression.

Introduction: Bone tissue engineering seeks innovative materials that support cell growth and regeneration. Electrospun nanofibers, with their high surface area and tunable properties, serve as promising scaffolds. This study explores the incorporation of flaxseed extract, rich in polyphenolic compounds, into polyvinyl alcohol (PVA) nanofibers to improve their application in bone tissue engineering. Methods: High-performance liquid chromatography (HPLC) identified ten key compounds in flaxseed extract, including polyphenolic acids and flavonoids. PVA nanofibers were fabricated with 30 wt.% flaxseed extract (P70/E30) via electrospinning. We optimized characteristics like diameter, hydrophilicity, swelling behavior, and hydrolytic degradation. MG-63 osteoblast cultures were used to assess scaffold efficacy through cell adhesion, proliferation, viability (MTT assay), and differentiation. RT-qPCR measured expression of osteogenic genes RUNX2, COL1A1, and OCN. Results: Flaxseed extract increased nanofiber diameter from 252 nm (pure PVA) to 435 nm (P70/E30). P70/E30 nanofibers showed higher cell viability (102.6% vs. 74.5% for pure PVA), although adhesion decreased (151 vs. 206 cells/section). Notably, P70/E30 enhanced osteoblast differentiation, significantly upregulating RUNX2, COL1A1, and OCN genes. Discussion: Flaxseed extract incorporation into PVA nanofibers enhances bone tissue engineering by boosting osteoblast proliferation and differentiation, despite reduced adhesion. These properties suggest P70/E30's potential for regenerative medicine, emphasizing scaffold optimization for biomedical applications.

Reactive oxygen-scavenging polydopamine nanoparticle coated 3D nanofibrous scaffolds for improved osteogenesis: Toward an aging in vivo bone regeneration model.

Tissue engineered scaffolds aimed at the repair of critical-sized bone defects lack adequate consideration for our aging society. Establishing an effective aged in vitro model that translates to animals is a significant unmet challenge. The in vivo aged environment is complex and highly nuanced, making it difficult to model in the context of bone repair. In this work, 3D nanofibrous scaffolds generated by the thermally-induced self-agglomeration (TISA) technique were functionalized with polydopamine nanoparticles (PD NPs) as a tool to improve drug binding capacity and scavenge reactive oxygen species (ROS), an excessive build-up that dampens the healing process in aged tissues. PD NPs were reduced by ascorbic acid (rPD) to further improve hydrogen peroxide (H2O2) scavenging capabilities, where we hypothesized that these functionalized scaffolds could rescue ROS-affected osteoblastic differentiation in vitro and improve new bone formation in an aged mouse model. rPDs demonstrated improved H2O2 scavenging activity compared to neat PD NPs, although both NP groups rescued the alkaline phosphatase activity (ALP) of MC3T3-E1 cells in presence of H2O2. Additionally, BMP2-induced osteogenic differentiation, both ALP and mineralization, was significantly improved in the presence of PD or rPD NPs on TISA scaffolds. While in vitro data showed favorable results aimed at improving osteogenic differentiation by PD or rPD NPs, in vivo studies did not note similar improvements in ectopic bone formation an aged model, suggesting that further nuance in material design is required to effectively translate to improved in vivo results in aged animal models.

Polysaccharide base electrospun nanofibrous scaffolds for cartilage tissue engineering: Challenges and opportunities.

Polysaccharides, known as naturally abundant macromolecular materials which can be easily modified chemically, have always attracted scientists' interest due to their outstanding properties in tissue engineering. Moreover, their intrinsic similarity to cartilage ECM components, biocompatibility, and non-harsh processing conditions make polysaccharides an excellent option for cartilage tissue engineering. Imitating the natural ECM structure to form a fibrous scaffold at the nanometer scale in order to recreate the optimal environment for cartilage regeneration has always been attractive for researchers in the past few years. However, there are some challenges for polysaccharides electrospun nanofibers preparation, such as poor solubility (Alginate, cellulose, chitin), high viscosity (alginate, chitosan, and Hyaluronic acid), high surface tension, etc. Several methods are reported in the literature for facing polysaccharide electrospinning issues, such as using carrier polymers, modification of polysaccharides, and using different solvent systems. In this review, considering the importance of polysaccharide-based electrospun nanofibers in cartilage tissue engineering applications, the main achievements in the past few years, and challenges for their electrospinning process are discussed. After careful investigation of reported studies in the last few years, alginate, chitosan, hyaluronic acid, chondroitin sulfate, and cellulose were chosen as the main polysaccharide base electrospun nanofibers used for cartilage regeneration.

Generation of cardiomyocytes from stem cells cultured on nanofibrous scaffold: Experimental approach for attenuation of myocardial infarction.

The current study was constructed to fabricate polyamide based nanofibrous scaffolds (NS) and to define the most promising one for the generation of cardiomyocytes from adipose tissue derived mesenchymal stem cells (ADMSCs). This purpose was extended to assess the potentiality of the generated cardiomyocytes in relieving myocardial infarction (MI) in rats. Production and characterization of NSs were carried out. ADMSCs were cultured on NS and induced to differentiate into cardiomyocytes by specific growth factors. Molecular analysis for myocyte-specific enhancer factor 2 C (MEF2C) and alpha sarcomeric actin (α-SCA) expression was done to confirm the differentiation of ADMSCs into cardiomyocytes for further transplantation into MI induced rats. Implantation of cells in MI afflicted rats boosted heart rate, ST height and PR interval and lessened P duration, RR, QTc and QRS intervals. Also, this type of medication minified serum lactate dehydrogenase (LDH) and creatine kinase-MB (CK-MB) enzymes activity as well as serum and cardiac troponin T (Tn-T) levels and upraised serum and cardiac α-SCA and cardiac connexin 43 (CX 43) levels. Microscopic feature of cardiac tissue sections of rats in the treated groups revealed great renovation in the cardiac microarchitecture. Conclusively, this attempt gains insight into a realistic strategy for recovery of MI through systemic employment of in vitro generated cardiomyocytes.

Functionalized BP@(Zn+Ag)/EPLA Nanofibrous Scaffolds Fabricated by Cryogenic 3D Printing for Bone Tissue Engineering.

This study fabricates a functionalized scaffold by cryogenic three-dimensional (3D) printing using an aminated poly-L-lactic acid (EPLA) solution containing nanosilver/zinc-coated black phosphorus (BP@(Zn+Ag)) nanocomposites. The nanocomposites are prepared by a green method of in situ photodeposition of silver and zinc nanoparticles (AgNPs and ZnNPs) on BP nanosheets (BPNs) under visible light irradiation without any chemical reductant. Scanning electron microscope (SEM) and X-ray energy dispersive spectrometer (EDS) confirm the uniform distribution of BP@(Zn+Ag) nanoparticles in the EPLA nanofibrous matrix. The in vitro tests show that the fabricated BP@(Zn+Ag)/EPLA nanofibrous scaffold exhibits excellent antibacterial activity (over 96%) against E. coli and S. aureus, as well as enhanced cell viability and osteogenic activity to facilitate the growth and differentiation of osteoblasts. The in vivo rat calvarial defect model also demonstrates that the BP@(Zn+Ag)/EPLA nanofibrous scaffold promotes new bone tissue formation around the implant site. Therefore, the prepared multifunctional 3D printed BP@(Zn+Ag)/EPLA nanofibrous scaffold has great potential for bone tissue engineering (BTE) applications.

Incorporating silver nanoparticles into electrospun nanofibers of casein/polyvinyl alcohol to develop scaffolds for tissue engineering.

Developing novel antimicrobial wound dressings that have the potential to address the challenges associated with chronic wounds is highly imperative in providing effective infection control and wound healing support. Biocompatible electrospun nanofibers with their high porosity and surface area enabling efficient drug loading and delivery have been investigated in this regard as viable candidates for chronic wound care. Here, we design Casein/Polyvinyl alcohol (CAN/PVA) nanofibers reinforced with silver nanoparticles (Ag NPs) by the electrospinning technique to develop diabetic wound healing scaffolds. The prepared samples were characterized using spectroscopic and electron microscopic techniques. The biocompatibility of the polymer samples were assessed using 3 T3 fibroblast cell lines and the maximum cell viability was found to 95 % at a concentration of 50 µg/mL for the prepared nanofibers. Scratch assay tests were also performed to analyze the wound healing activity of the nanofibers wherein they demonstrated increased migration and proliferation of fibroblast 3 T3 cells. Moreover, these nanofibers also exhibit antibacterial efficiency against Gram-negative bacteria, Escherichia coli (E.coli). Therefore, the antimicrobial nature of the electrospun nanofibers coupled with their moisture absorption properties and wound healing ability render them as effective materials for wound dressing applications.

Fabrication and evaluation of the regenerative effect of a polycaprolactone/chitosan nanofibrous scaffold containing bentonite nanoparticles in a rat model of deep second-degree burn injury.

Objectives: In the present study, we evaluated the effect of a nanofibrous scaffold including polycaprolactone (PCL), chitosan (CHT), and bentonite nanoparticles (Ben-NPS) on wound healing in order to introduce a novel dressing for burn wounds. Materials and Methods: PCL, PCL/CHT, and PCL/CHT/Ben-NPS nanofibrous scaffolds were fabricated by the electrospinning technique. Their structural and physiochemical characteristics were investigated by Fourier-transform infrared spectroscopy (FTIR) analysis, scanning electron microscopy (SEM), tensile strength, water contact angle, as well as, swelling and degradation profiles test. The disc diffusion assay was carried out to investigate the antibacterial potential of the scaffolds. In addition, the cell viability and proliferation ability of human dermal fibroblasts (HDFs) on the scaffolds were assessed using MTT assay as well as SEM imaging. The wound-healing property of the nanofibrous scaffolds was evaluated by histopathological investigations during 3,7, and 14 days in a rat model of burn wounds. Results: SEM showed that all scaffolds had three-dimensional, beadles-integrated structures. Adding Ben-NPS into the PCL/CHT polymeric composite significantly enhanced the mechanical, swelling, and antibacterial properties. HDFs had the most cell viability and proliferation values on the PCL/CHT/Ben-NPS scaffold. Histopathological evaluation in the rat model revealed that dressing animal wounds with the PCL/CHT/Ben-NPS scaffold promotes wound healing. Conclusion: The PCL/CHT/Ben-NPS scaffold has promising regenerative properties for accelerating skin wound healing.

Ultrasound stimulated piezoelectric barium titanate and boron nitride nanotubes in nonconductive poly-ε-caprolactone nanofibrous scaffold for bone tissue engineering.

Nanomaterials can provide unique solutions for the problems experienced in tissue engineering by improving a scaffold's physico-bio-chemical properties. With its piezoelectric property, bone is an active tissue with easy adaptation and remodeling through complicated mechanisms of electromechanical operations. Although poly(ε-caprolactone) (PCL) is an excellent polymer for bone tissue engineering, it is lack of conductivity. In this study, piezoelectric barium titanates (BaTiO3) and boron nitride nanotubes (BNNTs) are used as ultrasound (US) stimulated piezoelectric components in PCL to mimic piezoelectric nature of bone tissue. Electric-responsive Human Osteoblast cells on the scaffolds were stimulated by applying low-frequency US during cell growth. Biocompatibility, cell adhesion, alkaline phosphatase activities and mineralization of osteoblast cells on piezo-composite scaffolds were investigated. BaTiO3or BNNTs as reinforcement agents improved physical and mechanical properties of PCL scaffolds.In vitrostudies show that the use of BaTiO3or BNNTs as additives in non-conductive scaffolds significantly induces and increases the osteogenic activities even without US stimulation. Although BaTiO3is one of the best piezoelectric materials, the improvement is more dramatic in the case of BNNTs with the increased mineralization, and excellent chemical and mechanical properties.

Characterization and in vitro bioactivity evaluation of polyvinyl alcohol incorporated electro spun chitosan/ fluor apatite nanofibrous scaffold for bone tissue engineering.

In this study, polyvinyl alcohol/chitosan/fluor apatite scaffolds with different concentrations of polyvinyl alcohol of 0.075 g ml-1 and 0.1 g ml-1, respectively named A and B fabricated by electrospinning method to use in tissue engineering. By examining the scaffolds by FE-SEM, an appetite layer formation which was on the scaffold surface was clearly observable. Increasing the concentration of polyvinyl alcohol from 0.075 g ml-1 to 0.1 g ml-1 in the nanofibrous scaffolds improved degradation characteristic with an optimized value of 26 ± 2 and 42 ± 1 % after 28 days, respectively. The mean diameter of fibers both scaffolds was 405 nm and 212 nm, respectively. Furthermore, the percentage of porosity in both scaffolds was calculated as 84% and 91%, separately. The level of hydrophilicity of the scaffolds was measured by the dynamic contact angle method. Moreover, the increase in the percentage of polyvinyl alcohol led to the decrease in the average contact angle in scaffold A and scaffold B from 90° to 70°, respectively. The results of bone marrow culture test with MG-63 (NCBI C555) cell on the surface of scaffolds demonstrated not cytotoxicity in the resulting scaffolds as well as a suitable substrate for the adhesion and growth of the cells. According to our findings, the electrospun fluorapatite-incorporated-chitosan/polyvinyl alcohol scaffold could provide a new nanocomposite for biomedical applications.

Electroconductive Nanofibrous Scaffolds Enable Neuronal Differentiation in Response to Electrical Stimulation without Exogenous Inducing Factors.

Among the various biochemical and biophysical inducers for neural regeneration, electrical stimulation (ES) has recently attracted considerable attention as an efficient means to induce neuronal differentiation in tissue engineering approaches. The aim of this in vitro study was to develop a nanofibrous scaffold that enables ES-mediated neuronal differentiation in the absence of exogenous soluble inducers. A nanofibrous scaffold composed of polycaprolactone (PCL), poly-L-lactic acid (PLLA), and single-walled nanotubes (SWNTs) was fabricated via electrospinning and its physicochemical properties were investigated. The cytocompatibility of the electrospun composite with the PC12 cell line and bone marrow-derived mesenchymal stem cells (BMSCs) was investigated. The results showed that the PCL/PLLA/SWNT nanofibrous scaffold did not exhibit cytotoxicity and supported cell attachment, spreading, and proliferation. ES was applied to cells cultured on the nanofibrous scaffolds at different intensities and the expression of the three neural markers (Nestin, Microtubule-associated protein 2, and ß tubulin-3) was evaluated using RT-qPCR analysis. The results showed that the highest expression of neural markers could be achieved at an electric field intensity of 200 mV/cm, suggesting that the scaffold in combination with ES can be an efficient tool to accelerate neural differentiation in the absence of exogenous soluble inducers. This has important implications for the regeneration of nerve injuries and may provide insights for further investigations of the mechanisms underlying ES-mediated neuronal commitment.

Multifunctional electrospun nanofibrous scaffold enriched with alendronate and hydroxyapatite for balancing osteogenic and osteoclast activity to promote bone regeneration.

Electrospun composite nanofiber scaffolds are well known for their bone and tissue regeneration applications. This research is focused on the development of PVP and PVA nanofiber composite scaffolds enriched with hydroxyapatite (HA) nanoparticles and alendronate (ALN) using the electrospinning technique. The developed nanofiber scaffolds were investigated for their physicochemical as well as bone regeneration potential. The results obtained from particle size, zeta potential, SEM and EDX analysis of HA nanoparticles confirmed their successful fabrication. Further, SEM analysis verified nanofiber's diameters within 200-250 nm, while EDX analysis confirmed the successful incorporation of HA and ALN into the scaffolds. XRD and TGA analysis revealed the amorphous and thermally stable nature of the nanofiber composite scaffolds. Contact angle, FTIR analysis, Swelling and biodegradability studies revealed the hydrophilicity, chemical compatibility, suitable water uptake capacity and increased in-vitro degradation making it appropriate for tissue regeneration. The addition of HA into nanofiber scaffolds enhanced the physiochemical properties. Additionally, hemolysis cell viability, cell adhesion and proliferation by SEM as well as confocal microscopy and live/dead assay results demonstrated the non-toxic and biocompatibility behavior of nanofiber scaffolds. Alkaline phosphatase (ALP) and tartrate-resistant acid phosphatase (TRAP) assays demonstrated osteoblast promotion and osteoclast inhibition, respectively. These findings suggest that developed HA and ALN-loaded PVP/PVA-ALN-HA nanofiber composite scaffolds hold significant promise for bone regeneration applications.

Eradication of Pseudomonas aeruginosa biofilm using quercetin-mediated copper oxide nanoparticles incorporated in the electrospun polycaprolactone nanofibrous scaffold.

Pseudomonas aeruginosa is an opportunistic bacterial pathogen that form biofilms in chronic wounds and is difficult to treat with standard treatment methods. In the present study, flavonoid quercetin-mediated CuONPs (Que-CuONPs) were successfully synthesized and incorporated in the electrospun polycaprolactone (Que-CuONPs-PCL) nanofibrous membrane to eradicate the burn wound infection causing P. aeruginosa biofilm. The fabricated scaffold Que-CuONPs-PCL was characterized using HR-SEM, EDX, XRD, and FTIR. The synthesized Que-CuONPs appeared as spherical in shape with the average size of 36 nm. The crystallite size of the synthesized CuONPs was calculated as 23 nm. Antibacterial activity results shows that the ZOI and MIC of Que-CuONPs against P. aeruginosa was found to be 20 mm and 5 µg/mL, respectively. Antibiofilm assay results indicate the pre-formed P. aeruginosa biofilm was completely eradicated by Que-CuONPs at 8-MIC. The Que-CuONPs-PCL nanofibrous scaffolds exhibits less cytotoxic effects on mouse fibroblast (L929) cells. Finally, this study highlights the fabricated Que-CuONPs-PCL nanofibrous scaffolds exhibits an excellent antibiofilm effect against P. aeruginosa biofilm with a great biocompatibility.

Fabrication and Characterization of Zn Particle Incorporated Fibrous Scaffolds for Potential Application in Tissue Healing and Regeneration.

Zinc (Zn) metal and its alloys have received a lot of interest in biomedical applications due to their biodegradability, biocompatibility, antimicrobial activity, and ability to stimulate tissue regeneration. Bulk Zn has been successfully utilized in a variety of implant applications, most notably as bioabsorbable cardiac stents and orthopedic fixation devices, where it provides adequate mechanical properties while also releasing helpful Zn ions (Zn2+) during degradation. Such beneficial ions are dose-dependent and, when released in excess, can induce cellular toxicity. In this study, we hypothesize that embedding Zn metal particles into a polymer nanofibrous scaffold will enable control of the degradation and time release of the Zn2+. We designed and fabricated two polymer scaffolds, polycaprolactone (PCL) and polycaprolactone-chitosan (PCL-CH). Each scaffold had an increasing amount of Zn. Several physicochemical properties such as fiber morphology, crystallinity, mechanical strength, hydrophilicity, degradation and release of Zn2+, thermal properties, chemical compositions, and so forth were characterized and compared with the PCL fibrous scaffold. The biological properties of the scaffolds were evaluated in vitro utilizing direct and indirect cytotoxicity assays and cell viability. All the data show that the addition of Zn changed various physical properties of the PCL and PCL-CH scaffolds except their chemical structure. Further investigation reveals that the PCL-CH scaffolds degrade the Zn particles relatively faster than the PCL because the presence of the hydrophilic CH influences the faster release of Zn2+ in cell culture conditions as compared to the PCL fibrous scaffold. The combined advantages of CH and Zn in the PCL scaffold enriched 3T3 fibroblast cells' survival and proliferation except the ones with the higher concentration of Zn particles. These new composite scaffolds are promising and can be further considered for tissue healing and regeneration applications.

Radiographic evaluation of alveolar ridge preservation using a chitosan/polyvinyl alcohol nanofibrous matrix: A randomized clinical study.

The objective of this randomized clinical trial (RCT) was to assess the effectiveness of electrospun chitosan/polyvinyl alcohol (CS/PVA) nanofibrous scaffolds in preserving the alveolar ridge and enhancing bone remodeling following tooth extraction when compared to a control group. In this split RCT, 24 human alveolar sockets were randomly assigned to two groups, with 12 sockets receiving CS/PVA nanofibrous scaffold grafts (test group) and 12 left to heal by secondary intention as the control group. Cone-beam computed tomography (CBCT) was performed at two different time points: immediately after extraction (T0) and 4 months post-extraction (T4). After 4 months, linear vertical and horizontal radiographic changes and bone density of extraction sockets were assessed in both the test and control groups. The RCT included 12 patients (4 male and 8 female) with a mean age of 24 ± 3.37 years. The test group had a significantly lower mean vertical resorption vs the control group, with a mean difference of 1.1 mm (P < 0.05). Similarly, the control group's mean horizontal bone resorption was -2.01 ± 1.04 mm, while the test group had a significantly lower mean of -0.69 ± 0.41 mm, resulting in a mean difference of 1.35 mm (P < 0.05). Furthermore, the study group exhibited a significant increase in bone density (722.03 ± 131.17 HU) after 4 months compared to the control group (448.73 ± 93.23 HU). In conclusion, we demonstrated within the limitations of this study that CS/PVA nanofibrous scaffold significantly limited alveolar bone resorption horizontally and vertically and enhanced bone density in alveolar sockets after 4 months when compared to results in the control group (TCTR20230526005).

Electrospun Scaffolds as Antimicrobial Herbal Extract Delivery Vehicles for Wound Healing.

Herbal extracts have been used in traditional remedies since the earliest myths. They have excellent antimicrobial, anti-inflammatory, and antioxidant activities owing to various bioactive components in their structure. However, due to their inability to reach a target and low biostability, their use with a delivery vehicle has come into prominence. For this purpose, electrospun nanofibrous scaffolds have been widely preferred for the delivery and release of antimicrobial herbal extracts due to the flexibility and operational versatility of the electrospinning technique. Herein, we briefly reviewed the electrospun nanofibrous scaffolds as delivery systems for herbal extracts with a particular focus on the preclinical studies for wound-healing applications that have been published in the last five years. We also discussed the indirect effects of herbal extracts on wound healing by altering the characteristics of electrospun mats.

Preparation, characterization, and bioactivity of reinforced monetite with chitosan-gelatin electrospun composite scaffold for bone tissue engineering.

In this study, chitosan-gelatin-monetite (CGM)-based electrospun scaffolds have been developed that closely mimicked the microstructure and chemical composition of the extracellular matrix of natural bone. CGM-based nanofibrous composite scaffolds were prepared with the help of the electrospinning technique, post-cross-linked using ethyl(dimethylaminopropyl)carbodiimide and N-hydroxysuccinimide solution to improve their stability in an aqueous environment. The prepared chitosan/gelatin (CG) scaffold showed an average fiber diameter of 308 ± 17 nm, whereas 5 and 7 wt% monetite containing CGM5and CGM7scaffolds, exhibited an average fiber diameter of 287 ± 13 and 265 ± 9 nm, respectively, revealing the fine distribution of monetite particles on the fibrous surface. The distribution of monetite nanoparticles onto the CG nanofibrous surface was confirmed using x-ray diffraction, Fourier transform infrared, and EDAX. Moreover, the addition of 7 wt% monetite into the CG electrospun matrix increased their ultimate tensile strength from 7.62 ± 0.13 MPa in the CG scaffold to 14.34 ± 0.39 MPa in the CGM7scaffold. Simulated body fluid study and staining with alizarin red S (ARS) confirmed the higher mineralization ability of monetite-containing scaffolds compared to that revealed by the CG scaffold. The monetite incorporation into the CG matrix improved its osteogenic properties, including pre-osteoblast MG-63 cell adhesion, proliferation, and differentiation, when seeded with the cells. A higher degree of cellular adhesion, spreading, and migration was observed on the monetite-incorporated CG scaffold than that on the CG scaffold. From 3-(4, 5-dimethylthiazol-2-yl-2, 5-diphenyltetrazolium bromide) MTT assay, alkaline phosphatase activity, ARS staining, and immunocytochemistry study, the cultured cells discovered a more conducive microenvironment to proliferate and subsequently differentiate into osteoblast lineage in contact with CGM7nanofibers rather than that in CGM0and CGM5.In-vitroresults indicated that electrospun CGM-based composite scaffolds could be used as a potential candidate to repair and regenerate new bone tissues.

Overview of Electrospinning for Tissue Engineering Applications.

Tissue engineering (TE) is an emerging field of study that incorporates the principles of biology, medicine, and engineering for designing biological substitutes to maintain, restore, or improve tissue functions with the goal of avoiding organ transplantation. Amongst the various scaffolding techniques, electrospinning is one of the most widely used techniques to synthesise a nanofibrous scaffold. Electrospinning as a potential tissue engineering scaffolding technique has attracted a great deal of interest and has been widely discussed in many studies. The high surface-to-volume ratio of nanofibres, coupled with their ability to fabricate scaffolds that may mimic extracellular matrices, facilitates cell migration, proliferation, adhesion, and differentiation. These are all very desirable properties for TE applications. However, despite its widespread use and distinct advantages, electrospun scaffolds suffer from two major practical limitations: poor cell penetration and poor load-bearing applications. Furthermore, electrospun scaffolds have low mechanical strength. Several solutions have been offered by various research groups to overcome these limitations. This review provides an overview of the electrospinning techniques used to synthesise nanofibres for TE applications. In addition, we describe current research on nanofibre fabrication and characterisation, including the main limitations of electrospinning and some possible solutions to overcome these limitations.

Topically Applied Biopolymer-Based Tri-Layered Hierarchically Structured Nanofibrous Scaffold with a Self-Pumping Effect for Accelerated Full-Thickness Wound Healing in a Rat Model.

Wound healing has grown to be a significant problem at a global scale. The lack of multifunctionality in most wound dressing-based biopolymers prevents them from meeting all clinical requirements. Therefore, a multifunctional biopolymer-based tri-layered hierarchically nanofibrous scaffold in wound dressing can contribute to skin regeneration. In this study, a multifunctional antibacterial biopolymer-based tri-layered hierarchically nanofibrous scaffold comprising three layers was constructed. The bottom and the top layers contain hydrophilic silk fibroin (SF) and fish skin collagen (COL), respectively, for accelerated healing, interspersed with a middle layer of hydrophobic poly-3-hydroxybutyrate (PHB) containing amoxicillin (AMX) as an antibacterial drug. The advantageous physicochemical properties of the nanofibrous scaffold were estimated by SEM, FTIR, fluid uptake, contact angle, porosity, and mechanical properties. Moreover, the in vitro cytotoxicity and cell healing were assessed by MTT assay and the cell scratching method, respectively, and revealed excellent biocompatibility. The nanofibrous scaffold exhibited significant antimicrobial activity against multiple pathogenic bacteria. Furthermore, the in vivo wound healing and histological studies demonstrated complete wound healing in wounded rats on day 14, along with an increase in the expression level of the transforming growth factor-ß1 (TGF-ß1) and a decrease in the expression level of interleukin-6 (IL-6). The results revealed that the fabricated nanofibrous scaffold is a potent wound dressing scaffold, and significantly accelerates full-thickness wound healing in a rat model.

Sustained release of basic fibroblast growth factor in micro/nanofibrous scaffolds promotes annulus fibrosus regeneration.

Tissue engineering has promising applications in the treatment of intervertebral disc degeneration (IDD). The annulus fibrosus (AF) is critical for maintaining the physiological function of the intervertebral disc (IVD), but the lack of vessels and nutrition in AF makes it difficult to repair. In this study, we used hyaluronan (HA) micro-sol electrospinning and collagen type I (Col-I) self-assembly techniques to fabricate layered biomimetic micro/nanofibrous scaffolds, which released basic fibroblast growth factor (bFGF) to promote AF repair and regeneration after discectomy and endoscopic transforaminal discectomy. The bFGF enveloped in the core of the poly-L-lactic-acid (PLLA) core-shell structure was released in a sustained manner and promoted the adhesion and proliferation of AF cells (AFCs). Col-I could self-assemble on the shell of the PLLA core-shell scaffold to mimic the extracellular matrix (ECM) microenvironment, providing structural and biochemical cues for the regeneration of AF tissue. The in vivo studies showed that the micro/nanofibrous scaffolds promoted the repair of AF defects by simulating the microstructure of native AF tissue and inducing endogenous regeneration mechanism. Taken together, the biomimetic micro/nanofibrous scaffolds have clinical potential for the treatment of AF defects caused by IDD. STATEMENT OF SIGNIFICANCE: The annulus fibrosus (AF) is essential for the intervertebral disc (IVD) physiological function, yet it lacks vascularity and nutrition, making repair difficult. Micro-sol electrospinning technology and collagen type I (Col-I) self-assembly technique were combined in this study to create a layered biomimetic micro/nanofibrous scaffold that releases basic fibroblast growth factor (bFGF) to promote AF repair and regeneration. Col-I could mimic the extracellular matrix (ECM) microenvironment, in vivo, offering structural and biochemical cues for AF tissue regeneration. This research indicates that micro/nanofibrous scaffolds have clinical potential for treating AF deficits induced by IDD.

Recent Advances in Tissue-Engineered Cardiac Scaffolds-The Progress and Gap in Mimicking Native Myocardium Mechanical Behaviors.

Heart failure is the leading cause of death in the US and worldwide. Despite modern therapy, challenges remain to rescue the damaged organ that contains cells with a very low proliferation rate after birth. Developments in tissue engineering and regeneration offer new tools to investigate the pathology of cardiac diseases and develop therapeutic strategies for heart failure patients. Tissue -engineered cardiac scaffolds should be designed to provide structural, biochemical, mechanical, and/or electrical properties similar to native myocardium tissues. This review primarily focuses on the mechanical behaviors of cardiac scaffolds and their significance in cardiac research. Specifically, we summarize the recent development of synthetic (including hydrogel) scaffolds that have achieved various types of mechanical behavior-nonlinear elasticity, anisotropy, and viscoelasticity-all of which are characteristic of the myocardium and heart valves. For each type of mechanical behavior, we review the current fabrication methods to enable the biomimetic mechanical behavior, the advantages and limitations of the existing scaffolds, and how the mechanical environment affects biological responses and/or treatment outcomes for cardiac diseases. Lastly, we discuss the remaining challenges in this field and suggestions for future directions to improve our understanding of mechanical control over cardiac function and inspire better regenerative therapies for myocardial restoration.