Reinforcement of Injectable Hydrogel for Meniscus Tissue Engineering by Using Cellulose Nanofiber from Cassava Pulp

Abstract

Injectable hydrogels can be applied to treat damaged meniscus in minimally invasive conditions. Generally, injectable hydrogels can be prepared from various polymers such as polycaprolactone (PCL) and poly (N-isopropylacrylamide) (PNIPAAm). Poly (ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) block copolymer-diacrylate (PEO-PPO-PEO-DA) is an interesting polymer due to its biodegradability and can be prepared as water-insoluble injectable hydrogel after curing with UV light at low intensity. However, mechanical and cell adhesion properties are not optimal for these hydrogels. For the improved mechanical performance of the injectable hydrogel, cellulose nanofiber (CNF) extracted from cassava pulp was used as a reinforcing filler in this study. In addition, gelatin methacrylate (GelMA), the denatured form of collagen was used to enhance cell adhesion. PEO-PPO-PEO-DA/CNF/GelMA injectable hydrogels were prepared with 2-hydroxy-1-(4-(hydroxy ethoxy) phenyl)-2-methyl-1-propanone as a photoinitiator and then cured with UV light, 365 nm at 6 mW/cm2. Physicochemical characteristics of the hydrogels and hydrogels with CNF were studied in detail including morphology characterization, pore size diameter, porosity, mechanical properties, water uptake, and swelling. In addition, cell viability was also studied. CNF-reinforced injectable hydrogels were successfully prepared after curing with UV light within 10 min with a thickness of 2 mm. CNF significantly improved the mechanical characteristics of injectable hydrogels. The incorporation of GelMA into the injectable hydrogels improved the viability of human cartilage stem/progenitor cells. At optimum formulation, 12%PEO-PPO-PEO-DA/0.5%CNF/3%GelMA injectable hydrogels significantly promoted cell viability (> 80%) and also showed good physicochemical properties, which met tissue engineering requirements. In summary, this work shows that these novel injectable hydrogels have the potential for meniscus tissue engineering.

Current advances in engineering meniscal tissues: insights into 3D printing, injectable hydrogels and physical stimulation based strategies

“…Recently the facile and versatile photopolymerizing natural and synthetic polymers are on the rise in the field of tissue engineering due to their ease of applicability for fabrication of 3D architecture and inherent mechanical stability while being biologically active and compatible [254]. Jeencham et al demonstrated the use of an injectable hydrogel composed of cellulose nanofibers, gelatin methacrylate (gelMA) and PEO-PPO-PEO-DA for meniscus tissue engineering applications [255]. Chen et al integrated synovial aptamers within gelMA for the recruitment of endogenous cells for the repair of avascular meniscus lesions [256].…”

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.…”

“…F127 can be conjugated with other active groups via chemical modification. For example, Jeencham et al used F-127 diacrylate to create photo-crosslinked hydrogels with GelMA and CNF [55]. The resultant combination exhibited encouraging physicochemical and biological characteristics, indicating its potential for use in 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].…”