Effective wound healing on diabetic mice by adhesive antibacterial GNPs-lysine composited hydrogel.

Current trends in wound care research focus on creating dressings for diverse wound types, aiming to effectively control the wound healing process. We proposed a wound dressing composed of oxidized hyaluronic acid and amine gelatin with embedded lysine-modified gelatin nanoparticles (HGel-GNPs-lysine). This dressing improves mechanical properties and reduces degradation rates. The storage modulus for HGel-GNPs-lysine was 3,800 Pa, exceeding that of HGel (1,750 Pa). The positively charged surface of GNPs-lysine effectively eliminated Escherichia coli and Staphylococcus aureus. In a diabetic mice model (C57BL/6), HGel-GNPs-lysine immobilized with basic-fibroblast growth factor promoted granulation tissue thickness and collagen density. Gene expression analysis indicated that HGel-GNPs-lysine reduced inflammation and enhanced angiogenesis. This study highlights that HGel-GNPs-lysine could offer alternative treatment strategies for regulating the inflammatory response at the injury site in wound dressing applications.

Thiol-yne click crosslink hyaluronic acid/chitosan hydrogel for three-dimensional in vitro follicle development.

There is a great deal of potential for in vitro follicle growth to provide an alternative approach to fertility preservation. This strategy reduces the possibility of cancer cells re-exposure after transplantation, and it does not require hormone stimulation. Adopting a three-dimensional (3D) culture method helps preserve the architecture of the follicle and promotes the maturity of oocytes. In order to maintain follicle morphology, enhance the quality of mature oocytes, and facilitate meiotic spindle assembly, the current work aimed to develop the 3D in vitro preantral mouse follicle culture method. Thiolated chitosan-co-thiolated hyaluronic (CSHS) hydrogel was designed to evaluate the effects of biomaterials on ovarian follicle development. Isolated follicles from mouse ovaries were randomly divided into alginate (Alg) as a 3D control, thiolated hyaluronic acid (HASH), and CSHS groups. Single follicle was encapsulated in each hydrogel, and performed for 10 days and subsequently ovulated to retrieve mature oocytes on day 11. CSHS hydrogel promoted follicle survival and oocyte viability with maintained spherical morphology of follicle. Matured oocytes with normal appearance of meiotic spindle and chromosome alignment were higher in the CSHS group compared with those in the Alg and HASH groups. Furthermore, CSHS increased expression level of folliculogenesis genes (TGFß-1, GDF-9) and endocrine-related genes (LHCGR, and FSHR). With various experimental setups and clinical applications, this platform could be applied as an alternative method to in vitro follicle culture with different experimental designs and clinical applications in the long-term period.

Three-Dimensional Culture for In Vitro Folliculogenesis in the Aspect of Methods and Materials.

In vitro ovarian follicle culture is a reproduction technique used to obtain fertilizable oocytes, for overcoming fertility issues due to premature ovarian failure. This requires the establishment of an in vitro culture model that is capable of better simulating the in vivo ovarian growth environment. Two-dimensional (2D) culture systems have been successfully set up in rodent models. However, they are not suitable for larger animal models as the follicles of larger animals cultured in 2D culture systems often lose their shape due to dysfunction in the gap junctions. Three-dimensional (3D) culture systems are more suitable for maintaining follicle architecture, and therefore are proposed for the successful in vitro culturing of follicles in various animal models. The role of different methods, scaffolds, and suspension cultures in supporting follicle development has been studied to provide direction for improving in vitro follicle culture technologies. The three major strategies for in vitro 3D follicle cultures are discussed in this article. First, the in vitro culture systems, such as microfluidics, hanging drop, hydrogels, and 3D-printing, are reviewed. We have focused on the 3D hydrogel system as it uses different materials for supporting follicular growth and oocyte maturation in several animal models and in humans. We have also discussed the criteria used for biomaterial evaluations such as solid concentration, elasticity, and rigidity. In addition, future research directions for advancing in vitro 3D follicle culture system are discussed. Impact statement A new frontier in assisted reproductive technology is in vitro tissue or follicle culture, particularly for fertility preservation. The in vitro three-dimensional (3D) culture technique enhances follicular development and provides mature oocytes, overcoming the limitations of traditional in vitro two-dimensional cultures. Polymer biomaterials have good compatibility and retain the physiological structure of follicles in the 3D culture system. Utilizing hybrid in vitro culture materials by merging matrix, hydrogel, and unique patterned materials may facilitate follicular growth in the future.

Improvement of IgA Nephropathy and Kidney Regeneration by Functionalized Hyaluronic Acid and Gelatin Hydrogel.

BACKGROUND: Immunoglobulin A (IgA) nephropathy (IgAN) is one of an important cause of progressive kidney disease and occurs when IgA settles in the kidney resulted in disrupts kidney's ability to filter waste and excess water. Hydrogels are promising material for medical applications owing to their excellent adaptability and filling ability. Herein, we proposed a hyaluronic acid/gelatin (CHO-HA/Gel-NH2) bioactive hydrogel as a cell carrier for therapeutic kidney regeneration in IgAN. METHODS: CHO-HA/Gel-NH2 hydrogel was fabricated by Schiff-base reaction without any additional crosslinking agents. The hydrogel concentrations and ratios were evaluated to enhance adequate mechanical properties and biocompatibility for further in vivo study. High serum IgA ddY mice kidneys were treated with human urine-derived renal progenitor cells encapsulated in the hydrogel to investigate the improvement of IgA nephropathy and kidney regeneration. RESULTS: The stiffness of the hydrogel was significantly enhanced and could be modulated by altering the concentrations and ratios of hydrogel. CHO-HA/Gel-NH2 at a ratio of 3/7 provided a promising milieu for cells viability and cells proliferation. From week four onwards, there was a significant reduction in blood urea nitrogen and serum creatinine level in Cell/Gel group, as well as well-organized glomeruli and tubules. Moreover, the expression of pro-inflammatory and pro-fibrotic molecules significantly decreased in the Gel/Cell group, whereas anti-inflammatory gene expression was elevated compared to the Cell group. CONCLUSION: Based on in vivo studies, the renal regenerative ability of the progenitor cells could be further increased by this hydrogel system.

Crosslinking method of hyaluronic-based hydrogel for biomedical applications.

In the field of tissue engineering, there is a need for advancement beyond conventional scaffolds and preformed hydrogels. Injectable hydrogels have gained wider admiration among researchers as they can be used in minimally invasive surgical procedures. Injectable gels completely fill the defect area and have good permeability and hence are promising biomaterials. The technique can be effectively applied to deliver a wide range of bioactive agents, such as drugs, proteins, growth factors, and even living cells. Hyaluronic acid is a promising candidate for the tissue engineering field because of its unique physicochemical and biological properties. Thus, this review provides an overview of various methods of chemical and physical crosslinking using different linkers that have been investigated to develop the mechanical properties, biodegradation, and biocompatibility of hyaluronic acid as an injectable hydrogel in cell scaffolds, drug delivery systems, and wound healing applications.

Synthesis and Characterization of Gelatin-Based Crosslinkers for the Fabrication of Superabsorbent Hydrogels.

In this work, crosslinkers were prepared by conjugating high- and low-molecular-weight gelatin with different mole ratios of itaconic acid (IA) with double bonds. Then, the gelatin-itaconic acid (gelatin-IA) crosslinkers were compared with the gelatin-methacrylate (gelatin-MA) crosslinkers. The molecular weights and structures of gelatin-MA and gelatin-IA were confirmed using gel permeation chromatography (GPC) and nuclear magnetic resonance (NMR). Additionally, the swelling ratio and biodegradation properties of the hydrogels using IA as starting monomers and gelatin-IA and gelatin-MA as crosslinkers were investigated. Both hydrogels prepared with high and low molecular weights of gelatin-IA showed higher swelling ratios than those prepared with the gelatin-MA. The results also showed that absorbent hydrogels with different biodegradabilities and swelling ratios could be prepared by changing the ratio of the gelatin-based crosslinkers.