A porous collagen-based hydrogel and implantation method for corneal stromal regeneration and sustained local drug delivery

Abstract

Biomaterials designed to replace the diseased cornea could be used to treat corneal blindness where human donor tissue is in short supply, but challenges are the integration of biomaterials with host tissue and cells, avoiding a rapid material degradation and maintaining corneal transparency. Additionally, implantation surgery often triggers an aggressive wound healing response that can lead to corneal thinning and opacity. Here, we report a collagen-based hydrogel with transparency and mechanical properties suitable for replacing a substantial portion of a damaged or diseased corneal stroma. The porous hydrogel permitted migration and population by host cells while maintaining transparency and thickness six months after surgical implantation in an in vivo model of human corneal surgery. With a novel hybrid surgical implantation technique inspired by LASIK refractive surgery, rapid wound healing occurred around implants to maintain biomaterial integrity, transparency and function. Host stromal cell repopulation and regeneration of host epithelium and nerves were observed, as necessary steps towards corneal regeneration. Finally, as a proof-of-principle, the hydrogel loaded with a neuroregenerative drug achieved sustained slow-release drug delivery in vitro. The proposed hydrogel and novel implantation technique together represent a therapeutic approach with translational potential for replacing and regenerating diseased corneal stromal tissue.

3D printed biomimetic epithelium/stroma bilayer hydrogel implant for corneal regeneration

“…6 A exhibited that the cornea was wounded with a customized 3.5-mm vacuum trephine, and then 3D printed cell-laden or cell-free PEGDA-GelMA-20-5 hydrogel was put on the wounded area. Finally, two 8-shaped overlying sutures were used to hold the scaffold in place as reported previously [ 40 ]. During the whole implantation process, the scaffold was robust enough to be handled without collapse.…”

“…Then, the cell-laden or cell-free corneal scaffolds were punched with a trephine and carefully put on the corneal defect area with the printed epithelia layer facing upwards. Considering the risk of tearing the corneal scaffold by suturing, the construct was fixed with two 8-shaped overlying 10-0 sutures as previously reported method [ 40 ]. In the control group, only corneal defect was created and no hydrogel was placed.…”

Artificial Cornea: Past, Current, and Future Directions

“…Grafting outcomes in mini-pig corneas were superior to those in human subjects, indicating that animal models are only predictive for patients with non-severely pathological corneas ( 120 ). Another method to combat neovascularisation is to integrate a sustained release nanosystem of bevacizumab (an anti-VEGF drug) into the cell-free biosynthetic scaffolds ( 121 ), while ulceration and a neurotrophic deficit could be addressed by sustained release of nerve growth factor, demonstrated recently in a collagen-based scaffold releasing the drug in a controlled manner during a 60-day period ( 122 ).…”

Recent Advances in Biopolymeric Membranes towards the Removal of Emerging Organic Pollutants from Water

“…For example, carrageenan has been used in different sectors such as drug delivery, packaging, and food additives [28,95,96], whereas cellulose has been studied in drug delivery and textiles [97]. Starch has also been explored in food packaging [98,99]; fibrinogen in drug delivery and wound healing [100,101]; silk in wound healing [102,103]; collagen in tissue engineering [104][105][106] and drug delivery [107][108][109]; pullulan in drug delivery [110], food packaging, and food stabilizing [111,112]; alginate in biomedical applications [113,114]; chitin in tissue engineering [115] and enzyme immobilization [116,117]; and collagen in tissue engineering [104][105][106] and drug delivery [107][108][109]. However, our literature search demonstrated that biopolymers have limited applications in water treatment even though they possess useful properties such as hydrophilicity, an optical nature, and an easy-to-functionalize capacity.…”