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In this study, new types of hybrid double-network (DN) hydrogels composed of polyvinyl alcohol (PVA), chitosan (CH), and sodium alginate (SA) are introduced, with the hypothesis that this combination and incorporating multi-walled carbon nanotubes (MWCNTs) and graphene nanoplatelets (GNPs) will enhance osteogenetic differentiation and the structural and mechanical properties of scaffolds for bone tissue engineering applications. Initially, the impact of varying mass ratios of the PVA/CH/SA mixture on mechanical properties, swelling ratio, and degradability was examined. Based on this investigation, a mass ratio of 4:6:6 was determined to be optimal. At this ratio, the hydrogel demonstrated a Young's modulus of 47.5 ± 5 kPa, a swelling ratio of 680 ± 6 % after 3 h, and a degradation rate of 46.5 ± 5 % after 40 days. In the next phase, following the determination of the optimal mass ratio, CNTs and GNPs were incorporated into the 4:6:6 composite resulting in a significant enhancement in the electrical conductivity and stiffness of the scaffolds. The introduction of CNTs led to a notable increase of 36 % in the viability of MG63 osteoblast cells. Additionally, the inhibition zone test revealed that GNPs and CNTs increased the diameter of the inhibition zone by 49.6 % and 52.6 %, respectively., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Articular cartilage is an avascular and almost acellular tissue with limited self-regenerating capabilities. Although injectable hydrogels have garnered a lot of attention as a promising treatment, a biocompatible hydrogel with adequate mechanical properties is yet to be created. In this study, an interpenetrating network hydrogel comprised of chitosan and silk fibroin was created through electrostatic and hydrophobic bonds, respectively. The polymeric network of the scaffold combined an effective microenvironment for cell activity with enhanced mechanical properties to address the current issues in cartilage scaffolds. Furthermore, microspheres (MS) were utilized for a controlled release of methylprednisolone acetate (MPA), around ~75 % after 35 days. The proposed scaffolds demonstrated great mechanical stability with ~0.047 MPa compressive moduli and ~145 kPa compressive strength. Moreover, the degradation rate of the samples (~45 % after 35 days) was optimized to match neo-cartilage formation. Furthermore, the use of natural biomaterials yielded good biocompatibility with ~76 % chondrocyte viability after 7 days. According to gross observation after 12 weeks the defect site of the treated groups was filled with minimally discernible boundary. These results were confirmed by histopathology assays were the treated groups showed higher chondrocyte count and collagen type II expression., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

In the present study, a hybrid microsphere/hydrogel system, consisting of polyvinyl alcohol (PVA)/sodium alginate (SA) hydrogel incorporating PCL microspheres is introduced as a skin scaffold to accelerate wound healing. The hydrogel substrate was developed using the freeze-thawing method, and the proportion of the involved polymers in its structure was optimized based on the in-vitro assessments. The bFGF-encapsulated PCL microspheres were also fabricated utilizing the double-emulsion solvent evaporation technique. The achieved freeze-dried hybrid system was then characterized by in-vitro and in-vivo experiments. The results obtained from the optimization of the hydrogel showed that increasing the concentration of SA resulted in a more porous structure, and higher swelling ability, elasticity and degradation rate, but decreased the maximum strength and elongation at break. The embedding of PCL microspheres into the optimized hydrogel structure provided sustained and burst-free release kinetics of bFGF. Besides, the addition of drug-loaded microspheres led to no significant change in the degradation mechanism of the hydrogel substrate; however, it reduced its mechanical strength. Furthermore, the MTT assay represented no cytotoxic effect for the hybrid system. The in-vivo studies on a burn-wound rat model, including the evaluation of the wound closure mechanism, and histological analyses indicated that the fabricated scaffold efficiently contributed to promoting cell-induced tissue regeneration and burn-wound healing.

This study presents a bilayer structure as a skin scaffold comprised of an electrospun sheet layer made of polycaprolactone and polyvinil alcohol and a porous hydrogel layer made of chitosan and gelatin. The hydrogel layer was fabricated by employing the freeze-gelation technique. The bilayer structure was achieved by pouring the hydrogel solution on the electrospun sheet at the bottom of a mold followed by the freeze-gelation technique to obtain a porous structure in the hydrogel. The hydrogel and hydrogel-electrospun samples were characterized by scanning electron microscopy, swelling, tensile strength, in vitro and in vivo analyses. From a mechanical strength standpoint, the combination of hydrogel and electrospun layers produced 110 and 133% increases in mean tensile strength and elastic modulus values, respectively compared to the single layer hydrogel sample. While the results of swelling and cell proliferation tests did not yield significant differences between the two groups, the bilayer scaffold performed better considering the results of the in vivo analysis. It was also seen that there was a good connection between the two layers in the bilayer scaffold, making the necessary manipulations and clinical handling convenient., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Native grafts such as internal mammary artery and saphenous vein are the main choice for coronary artery bypass graft. However, due to the limitations associated with their availability and rapid failure caused by hyperplasia, small diameter tissue-engineered vascular grafts (TEVGs) with sufficient post-implantation patency are urgently demanded as artificial alternatives. In our previous work, we innovatively fabricated a bilayer vascular graft providing appropriate structural and biological properties using electrospinning and freeze-drying methods. It was proved that the mechanical properties of the proposed graft enhanced in comparison with using either of methods individually. Here, we adopted the same methods and incorporated an anticoagulant internal layer (inner diameter 4 mm), comprised of co-electrospun fibers of silk fibroin (SF) and heparinized thermoplastic polyurethane (TPU), and an external highly porous hydrogel fabricated by freeze-drying method. The electrospun layer exhibited strong mechanical properties including superior elastic modulus (4.92 ± 0.11 MPa), suture retention force (6.73 ± 0.83 N), elongation at break (196 ± 4%), and comparable burst pressure (1140 ± 12 mmHg) while the external hydrogel provided SMCs viability. The heparin was released in a sustain manner over 40 days, and the cytocompatibility and blood compatibility of scaffold were approved using MTT assay and platelet adhesion test. Thus, the proposed graft has a potential to be used as an artificial blood vessel scaffold for later in-vivo transplantation. [ABSTRACT FROM AUTHOR]

Fabricating a biocompatible small-diameter vascular graft (< 6 mm) with mechanical properties similar to the natural vein and adding good anti-thrombogenic, endothelialization, and hyperplasia properties remains a challenge. To this end, we fabricated a heparinized bilayer graft to address this problem. The proposed bilayer sample consisted of a heparinized polycaprolactone (PCL), polyurethane (PU), and gelatin (G) co-electrospun inner layer and chitosan, gelatin, and silk fibroin freeze-dried hydrogel crosslinked with 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC) and N-hydroxysuccinimide (NHS) outer layer. The samples exhibited great ultimate stress, Young's module, and suture retention of 4.16 ± 0.25 MPa , 8.24 ± 2.59 MPa and 4.83 ± 0.31 N , respectively. The heparin release assay indicated a sustained release profile of around 70 % after 4 weeks, which can be attributed to the excellent control via emulsion. Furthermore, the heparinized samples demonstrated good anti-thrombogenic properties investigated in the platelet adhesion assay. For the outer layer, the hydrogel crosslinked with non-toxic materials was prepared through the freeze-drying method to achieve high porosity (64.63 %), suitable for smooth muscle cell activity. Moreover, inner and outer layers showed high cell viability toward endothelial (78.96 %) and smooth muscle cells (57.77 %), respectively. Overall, the proposed heparinized graft exhibited excellent potential for vascular graft regeneration. [Display omitted] [ABSTRACT FROM AUTHOR]

The replication of skin's dermal and epidermal morphology within a full-thickness wound using a bi-layer hydrogel to cater to their distinct needs is a compelling pursuit. Moreover, human placenta extract (HPE), containing a diverse array of bioactive agents, has proven to be effective in promoting the wound healing process and enhancing epidermal keratinocytes. This study presents a multifunctional bi-layer hydrogel incorporating HPE for accelerating full-thickness wound healing through sustained HPE release, inhibition of bacteria invasion, and promotion of cell proliferation. The upper layer of the scaffold, known as the dressing layer, is composed of carboxymethyl cellulose and sodium alginate, serving as a supportive layer for cell proliferation. The under layer, referred to as the regenerative layer, is composed of chitosan and gelatin, providing an extracellular matrix-like, porous, moist, and antibacterial environment for cell growth. The scaffold was optimized to replicate the morphology of the dermal and epidermal layers, with suitable fibroblast infiltration and a pore size of approximately 283 μm. Furthermore, the degradation rate of the samples matched the wound healing rate and persisted throughout this period. The sustained HPE release rate, facilitated by the degradation rate, was optimized to reach ~ 98 % after 28 days, covering the entire healing period. The samples demonstrated robust antibacterial capabilities, with bacterial inhibition zone diameters of 2.56 ± 0.10 cm and 2.63 ± 0.12 cm for S. aureus and E. coli , respectively. The biocompatibility of the samples remained at approximately 68.33 ± 4.5 % after 21 days of fibroblast cell culture. The in vivo experiment indicated that the HPE@Bilayer hydrogel promotes the formation of new blood vessels and fibroblasts during the early stages of healing, leading to the appropriate formation of granulation tissue and a wound contraction rate of (79.31 ± 3.1) %. Additionally, it resulted in the formation of a thick epidermal layer (keratinization) that effectively covered all the impaired areas, achieving a wound contraction rate of 95.83 ± 6.3 % at the late stage of wound healing. Furthermore, immunohistochemistry staining for CD31 and TGF-β revealed that the HPE@Bilayer group had 22 blood vessels/field and 34 % − 66 % immunoactive cells, respectively, after 14 days of healing. However, by day 21, angiogenesis and TGF-β expression had declined, demonstrating that the wounds had been successfully treated with minimal scarring. [ABSTRACT FROM AUTHOR]

[Display omitted] Injectable hydrogels are a promising treatment option for nervous system injuries due to the difficulty to replace lost cells and nervous factors but research on injectable conductive hydrogels is limited and these scaffolds have poor electromechanical properties. This study developed a chitosan/beta-glycerophosphate/salt hydrogel and added conductive aligned nanofibers (polycaprolactone/gelatin/single-wall carbon nanotube (SWCNT)) for the first time and inspired by natural nerve tissue to improve their biochemical and biophysical properties. The results showed that the degradation rate of hydrogels is proportional to the regrowth of axons and these hydrogels' mechanical (hydrogels without nanofibers or SWCNTs and hydrogels containing these additions have the same Young's modulus as the brain and spinal cord or peripheral nerves, respectively) and electrical properties, and the interconnective structure of the scaffolds have the ability to support cells. [ABSTRACT FROM AUTHOR]

Herein, a hybrid hydrogel/microsphere system is introduced for accelerated wound healing by sustained release of basic fibroblast growth factor (bFGF). The hydrogel is composed of a mixture of PVA, gelatin and chitosan. The double-emulsion-solvent-evaporation method was utilized to obtain microspheres composed of PCL, as the organic phase, and PVA, as the aqueous phase. Subsequently, various in-vitro and in-vivo assays were performed to characterize the system. BSA was used to optimize the release mechanism, and encapsulation efficiency in microspheres, where a combination of 3% (w/v) PCL and 1% (w/v) PVA was found to be the optimum microsphere sample. Incorporation of microspheres within the hydrogel substrate also led to a zero-order release kinetics. Results from SEM images, also represented an average porosity of 54%, and average mean pore size of 35 ± 7 μm for the hydrogel system, and the diameter of 5 ± 2 μm for the microspheres. Moreover, in vivo study including wound healing process, and histological analysis regarding re-epithelization, angiogenesis, inflammation, fibroblast genesis and collagen formation were performed using Hematoxyline-Eosin (H&E) staining, Periodic Acid–Schiff (PAS) staining and Masson’s Trichrome staining. In-vivo results represented that sustained delivery of bFGF promoted by biocompatibility of PVA/chitosan/gelatin hydrogel, significantly contribute to accelerated wound healing. [ABSTRACT FROM AUTHOR]

In this study, fabrication of a three-dimensional porous scaffold was performed using freeze gelation method. Recently, fabrication of scaffolds using polymer blends has become common for many tissue engineering applications due to their unique tunable properties. In this work, we fabricated alginate-gelatin porous hydrogels for wound healing application using a new method based on some modifications to the freeze-gelation method. Alginate and gelatin were mixed in three different ratios and the resulting solutions underwent freeze gelation to obtain 3D porous matrices. We analyzed the samples using different characterization tests. The scanning electron microscopy (SEM) results indicated that the freeze gelation method was successful in obtaining porous morphologies for all the fabricated alginate-gelatin samples as previously was seen in single-polymer fabrication using this method. The alginate to gelatin ratio affected swelling, biodegradation, cell culture and mechanical properties of the matrices. The scaffold with the lowest content of gelatin had the highest swelling ratio while biodegradation and cell proliferation and viability were increased with the gelatin content. Regarding the mechanical properties, as the gelatin content increased, the scaffold became more ductile and showed higher tensile strength. The in-vivo results also showed the biocompatibility of the blend scaffold and its positive role in wound healing process in rats. The low-cost procedure used in this study to fabricate the porous alginate-gelatin scaffolds can be adapted and modified to suit different tissue engineering applications. • A porous alginate-gelatin scaffold for wound healing was fabricated using freeze-gelation. • Varying gelatin concentrations were tested to optimize porosity, mechanical properties and biocompatibility. • The fabricated Alginate-Gelatin improved the healing of burn wounds significantly. • The low-cost method is capable of making porous matrices from polymer blends. [ABSTRACT FROM AUTHOR]