3D-bioprinted GelMA/gelatin/amniotic membrane extract (AME) scaffold loaded with keratinocytes, fibroblasts, and endothelial cells for skin tissue engineering.

Gelatin-methacryloyl (GelMA) is a highly adaptable biomaterial extensively utilized in skin regeneration applications. However, it is frequently imperative to enhance its physical and biological qualities by including supplementary substances in its composition. The purpose of this study was to fabricate and characterize a bi-layered GelMA-gelatin scaffold using 3D bioprinting. The upper section of the scaffold was encompassed with keratinocytes to simulate the epidermis, while the lower section included fibroblasts and HUVEC cells to mimic the dermis. A further step involved the addition of amniotic membrane extract (AME) to the scaffold in order to promote angiogenesis. The incorporation of gelatin into GelMA was found to enhance its stability and mechanical qualities. While the Alamar blue test demonstrated that a high concentration of GelMA (20%) resulted in a decrease in cell viability, the live/dead cell staining revealed that incorporation of AME increased the quantity of viable HUVECs. Further, gelatin upregulated the expression of KRT10 in keratinocytes and VIM in fibroblasts. Additionally, the histological staining results demonstrated the formation of well-defined skin layers and the creation of extracellular matrix (ECM) in GelMA/gelatin hydrogels during a 14-day culture period. Our study showed that a 3D-bioprinted composite scaffold comprising GelMA, gelatin, and AME can be used to regenerate skin tissues.

Correction: ECM-based bioadhesive hydrogel for sutureless repair of deep anterior corneal defects.

Correction for 'ECM-based bioadhesive hydrogel for sutureless repair of deep anterior corneal defects' by Safieh Boroumand et al., Biomater. Sci., 2024, https://doi.org/10.1039/d4bm00129j.

ECM-based bioadhesive hydrogel for sutureless repair of deep anterior corneal defects.

Corneal transplantation is the gold standard treatment for corneal-related blindness; however, this strategy faces challenges such as limited donor cornea, graft rejection, suture-related complications, and the need for specialized equipment and advanced surgical skills. Development of tissue adhesives for corneal regeneration is of great clinical value. However, currently available corneal tissue sealants pose challenges, such as lack of safety, biocompatibility, and desired mechanical properties. To meet these requirements simultaneously, a bovine stromal corneal extracellular matrix (dCor) was used to design a bioadhesive photocurable hydrogel based on gelatin methacrylate (GelMA) and polyethylene glycol diacrylate (PEGDA) hydrogels (dCor/Gel-PEG). Integration of dCor into the dual networks of GelMA and PEGDA (Gel-PEG) led to a bioadhesive hydrogel for curing corneal defects, which could be crosslinked by Irgacure 2959 within 5 min ultraviolet irradiation. The viability of corneal stromal stem cells (CSSCs) was improved on the dCor/Gel-PEG hydrogel in comparison to the Gel-PEG hydrogel. The gene expression profile supported the keratocyte differentiation of CSSCs seeded on dCor/Gel-PEG via increased KERA and ALDH, with inhibited myofibroblast transdifferentiation via decreased α-SMA due to the presence of dCor. Interestingly, the dCor/Gel-PEG hydrogel exhibited favorable mechanical performance in terms of elasticity and bioadherence to the host corneal stroma. Ex vivo and in vivo examinations proved the feasibility of this hydrogel for the sutureless reconstruction of deep anterior corneal defects with promising histopathological results.

Preparation and characterization of 3D bioprinted gelatin methacrylate hydrogel incorporated with curcumin loaded chitosan nanoparticles for in vivo wound healing application.

This study developed a biomimetic composite bioink consisting of gelatin methacrylate (GelMA) /chitosan nanoparticles (CSNPs) for extrusion-based 3D bioprinting. Additionally, curcumin(Cur)-loaded nanoparticles were incorporated which increased the proliferation and antibacterial activity of biomimetic skin constructs. The hydrogel, curcumin-loaded NPs, and the biocomposite was characterized chemically and physically. The results indicated proper modified gelatin with tunable physical characteristics, e.g., swelling ratio and biodegradability up to 1200 % and 25 days, respectively. In addition, the characterized CSNPs showed good distribution with a size of 370 nm and a zeta potential of 41.1 mV. We investigated the mechanical and cytocompatibility properties of chitosan nanoparticles encapsulated in hydrogel for emulating an extracellular matrix suitable for skin tissue engineering. CSNPs entrapped in GelMA (15 % w/v) exhibited controlled drug release during 5 days, which was fitted into various kinetic models to study the mass transfer mechanism behavior. Also, the composite hydrogels were effective as a barrier against both gram-positive and gram-negative bacteria at a concentration of 50 µg/ml nanoparticles in GelMA 15 %. Furthermore, the biocomposite was applied on Wistar rats for wound healing. As a result, this study provides a GelMA-NP50-Cur3 scaffold that promotes cell proliferation and decreases microbial infections in wounds.

Synthesis and characterization of a novel, pH-responsive sustained release nanocarrier using polyethylene glycol, graphene oxide, and natural silk fibroin protein by a green nano emulsification method to enhance cancer treatment.

In this study, for the first time, by employing a simple and efficient double nano-emulsification method and using sweet almond oil as the organic phase, polyethylene glycol (PEG)/graphene oxide (GO)/silk fibroin (SF) hydrogel-nanocomposite was synthesized. The aim of the research was to fabricate a biocompatible targeted pH-sensitive sustained release carrier, improve the drug loading capacity and enhance the anticancer effect of doxorubicin (DOX) drug. The obtained values for the entrapment (%EE) and loading efficacy (%LE) were 87.75 ± 0.7 % and 46 ± 1 %, respectively, and these high values were due to the use of GO with a large specific surface area and the electrostatic interaction between the drug and SF. The Fourier transform infrared spectroscopy (FTIR) and X-ray diffraction (XRD) analyses confirmed the presence of all the components in the nanocomposite and the suitable interaction between them. Based on the results of dynamic light scattering analysis (DLS) and zeta potential analysis, the mean size of the carrier particles and its surface charge were 293.7 nm and -102.9 mV, respectively. The high negative charge was caused by the presence of hydroxyl groups in GO and SF and it caused proper stability of the nanocomposite. The spherical core-shell structure with its homogeneous surface was also observed in the field emission scanning electron microscopy (FE-SEM) image. The cumulative release percentage of the nanocarrier reached 95.75 after 96 h and it is higher in the acidic environment at all times. The results of fitting the release data to the kinetic models suggested that the mechanism of release was dissolution-controlled anomalous at pH 7.4 and diffusion-controlled anomalous at pH 5.4. The results of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay and flow cytometry showed an increase in toxicity on MCF-7 cells and improved apoptotic cell death compared to the free drug. Consequently, the findings of this research introduced and confirmed PEG/GO/SF nanocomposite as an attractive novel drug delivery system for pH-sensitive and sustained delivery of chemotherapeutic agents in biomedicine.

PVA-Based Nanofibers Containing Chitosan Modified with Graphene Oxide and Carbon Quantum Dot-Doped TiO2 Enhance Wound Healing in a Rat Model.

Electrospun nanofibrous constructs based on nanoparticles and biopolymers have recently been used in tissue engineering because of their similarity to the extracellular matrix in nature. In this study, electrospun chitosan-carbon quantum dot-titanium dioxide-graphene oxide (CS-CQD-TiO2-GO) nanofibrous mats were synthesized for use as wound dressings by the electrospinning method. To increase the biodegradation rate and water resistance, the fabricated nanofibrous mats were cross-linked. SEM images showed a uniform and coherent structure of CS-CQD-TiO2-GO nanocomposites and CS-CQD-TiO2-GO electrospun nanofibers mats. FTIR analysis, XRD pattern, SEM mapping, and EDS spectrum demonstrate the accuracy of the synthesis as well as the elemental and chemical structure of the nanofibrous mat. The water contact angle indicated that the nanofibrous mat had a hydrophilic property, which is essential for controlling wound exudates. The tensile strength and elongation tests showed that the nanofibrous mat has suitable mechanical properties for wound dressing, including significant flexibility and strength. Interestingly, antimicrobial testing illustrated that the fabricated nanofibrous mat had antibacterial activity against Gram-negative and Gram-positive bacteria. Appropriate cell viability and cytocompatibility of treated mouse fibroblast NIH3T3 cells with the nanofibrous mat were determined using an MTT assay. The animal study results confirmed the proper potential of the nanofibrous mat in wound dressing applications.