Biopolymeric corneal lenticules by digital light processing based bioprinting: a dynamic substitute for corneal transplant.

Digital light processing (DLP) technology has gained significant attention for its ability to construct intricate structures for various applications in tissue modeling and regeneration. In this study, we aimed to design corneal lenticules using DLP bioprinting technology, utilizing dual network bioinks to mimic the characteristics of the human cornea. The bioink was prepared using methacrylated hyaluronic acid and methacrylated gelatin, where ruthenium salt and sodium persulfate were included for mediating photo-crosslinking while tartrazine was used as a photoabsorber. The bioprinted lenticules were optically transparent (85.45% ± 0.14%), exhibited adhesive strength (58.67 ± 17.5 kPa), and compressive modulus (535.42 ± 29.05 kPa) sufficient for supporting corneal tissue integration and regeneration. Puncture resistance tests and drag force analysis further confirmed the excellent mechanical performance of the lenticules enabling their application as potential corneal implants. Additionally, the lenticules demonstrated outstanding support for re-epithelialization and stromal regeneration when assessed with human corneal stromal cells. We generated implant ready corneal lenticules while optimizing bioink and bioprinting parameters, providing valuable solution for individuals suffering from various corneal defects and waiting for corneal transplants.

Kuragel: A biomimetic hydrogel scaffold designed to promote corneal regeneration.

Cornea-related injuries are the most common cause of blindness worldwide. Transplantation remains the primary approach for addressing corneal blindness, though the demand for donor corneas outmatches the supply by millions. Tissue adhesives employed to seal corneal wounds have shown inefficient healing and incomplete vision restoration. We have developed a biodegradable hydrogel - Kuragel, with the ability to promote corneal regeneration. Functionalized gelatin and hyaluronic acid form photo-crosslinkable hydrogel with transparency and compressive modulus similar to healthy human cornea. Kuragel composition was tuned to achieve sufficient adhesive strength for sutureless integration to host tissue, with minimal swelling post-administration. Studies in the New Zealand rabbit mechanical injury model affecting corneal epithelium and stroma demonstrate that Kuragel efficiently promotes re-epithelialization within 1 month of administration, while stroma and sub-basal nerve plexus regenerate within 3 months. We propose Kuragel as a regenerative treatment for patients suffering from corneal defects including thinning, by restoration of transparency and thickness.

Sulfated polysaccharide mediated TGF-ß1 presentation in pre-formed injectable scaffolds for cartilage tissue engineering.

In this work, a plant-derived polysaccharide carboxymethylcellulose (CMC) was chemically modified to incorporate sulfate groups to facilitate binding of cationic growth factors. The sulfated CMC (heparin mimic) was then used with CMC (glycosaminoglycan mimic) and gelatin (collagen mimic) to fabricate injectable pre-formed, macroporous scaffolds for cartilage tissue engineering. These scaffolds demonstrated high resilience and shape memory, thereby making them injectable through a 14G needle for up to 4-6 aspiration and injection cycles. Further, the scaffolds could sequester cationic proteins and growth factors (TGF-ß1) through affinity-based interactions. When seeded with infrapatellar fat pad derived MSCs, the scaffolds demonstrated enhanced chondrogenesis after 28 days of in vitro culture when compared to controls. Taken together; these results demonstrate a polysaccharide-based minimally-invasive and translatable pre-formed injectable scaffold-based cell and growth factor delivery system for cartilage regeneration.