Development of Poly(vinyl alcohol) Grafted Glycidyl Methacrylate/Cellulose Nanofiber Injectable Hydrogels for Meniscus Tissue Engineering

Abstract

This study aimed to develop poly (vinyl alcohol) grafted glycidyl methacrylate/cellulose nanofiber (PVA-g-GMA/CNF) injectable hydrogels for meniscus tissue engineering. PVA-g-GMA is an interesting polymer for preparing cross-linking injectable hydrogels with UV radiation, but it has poor mechanical properties and low cell proliferation. In this study, CNF as a reinforcing agent was selected to improve mechanical properties and cell proliferation in PVA-g-GMA injectable hydro-gels. The effect of CNF concentration on hydrogel properties was investigated. Both PVA-g-GMA and PVA-g-GMA hydrogels incorporating 0.3, 0.5, and 0.7% (w/v) CNF can be formed by UV curing at a wavelength of 365 nm, 6 mW/cm2 for 10 min. All hydrogels showed substantial microporosity with interconnected tunnels, and a pore size diameter range of 3–68 µm. In addition, all hydrogels also showed high physicochemical properties, a gel fraction of 81–82%, porosity of 83–94%, water content of 73–87%, and water swelling of 272–652%. The water content and swelling of hydrogels were increased when CNF concentration increased. It is worth noting that the reduction of porosity in the hydrogels occurred with increasing CNF concentration. With increasing CNF concentration from 0.3% to 0.7% (w/v), the compressive strength and compressive modulus of the hydrogels significantly increased from 23 kPa to 127 kPa and 27 kPa to 130 kPa, respectively. All of the hydrogels were seeded with human cartilage stem/progenitor cells (CSPCs) and cultured for 14 days. PVA-g-GMA hydrogels incorporating 0.5% and 0.7% (w/v) CNF demonstrated a higher cell proliferation rate than PVA-g-GMA and PVA-g-GMA hydrogels incorporating 0.3% (w/v) CNF, as confirmed by MTT assay. At optimum formulation, 10%PVA-g-GMA/0.7%CNF injectable hydrogel met tissue engineering requirements, which showed excellent properties and significantly promoted cell proliferation, and has a great potential for meniscus tissue engineering application.

Advances in Hydrogels for Meniscus Tissue Engineering: A Focus on Biomaterials, Crosslinking, Therapeutic Additives

“…Hydrogels composed of natural biomaterials have similar advantages as natural ECMs because the materials are extracted from plants or animals, which possess biocompatibility, biodegradability, and bioactivity, making them suitable for biomedical applications [46]. Commonly used natural materials and their derivatives include proteins (Figure 2; Table 1): collagen type I (COL I) [40,[47][48][49][50], gelatin (Gel) [24,51,52] and gelatin methacrylate (GelMA) [42,43,[53][54][55], fibrinogen (FB) [38,[56][57][58][59]; silk fibroin (SF) [41], polysaccharides (Figure 2; Table 1) such as hyaluronic acid (HA) [47,50] and tyramine-modified hyaluronic acid (TA-HA) [60], alginate (Alg) [61][62][63][64] and alginate dialdehyde (ADA) [51], agarose (Ag) [42,43,65], cellulose [55,61,66], chondroitin sulfate (CS) [67], and chitosan (Chi) [37,68]. Additionally, the utilization of native meniscus extracts (Figure 2; Table 1), also referred to as menisc...…”

“…These characteristics make it an ideal material for use as a support structure in hydrogel systems. The incorporation of cellulose nanofibers has substantially improved the mechanical properties of injectable hydrogels, offering great potential for applications in MTE [55,66] considering the vital importance of mechanical strength in meniscus scaffolds.…”

“…PVA also contains hydroxyl groups in its repeating units, which can be readily modified to create PVA derivatives. A recent study conducted by Sinna et al synthesized PVA-grafted glycidyl methacrylate (PVA-g-GMA) with photo-crosslinking ability [66]. They developed an injectable hydrogel containing 10% PVA-g-GMA and 0.7% cellulose nanofiber (CNF) for meniscus repair.…”

“…Photo-crosslinking is a commonly employed technique for creating hydrogels in the field of MTE [54,55,66]. The gelation mechanism involves the use of free radicals generated by photo-initiators in response to visible light or ultraviolet radiation, which then initiates the polymerization of hydrogel components containing carbon-carbon double bonds [116].…”