Digital light processing-bioprinted poly-NAGA-GelMA-based hydrogel lenticule for precise refractive errors correction.
Shuo JiaJirong YangAaron Dzi-Shing LauFushun ChenYashan BuErlong CaiHuogang WangHerng-Ee ChiengTianhao SunZhou ZhiyongChangshun RuanWilliam W LuJonathan Cheuk-Hung ChanPublished in: Biofabrication (2023)
Refractive disorder is the most prevalent cause of visual impairment worldwide. While treatment of refractive errors can bring improvement to quality of life and socio-economic benefits, there is a need for individualization, precision, convenience, and safety with the chosen method. Herein, we propose using pre-designed refractive lenticules based on poly-NAGA-GelMA (PNG) bio-inks photo-initiated by digital light processing (DLP)-bioprinting for correcting refractive errors. DLP-bioprinting allows PNG lenticules to have individualized physical dimensions with precision achievable to 10 micron (μm). Material characteristics of PNG lenticules in tests included optical and biomechanical stability, biomimetical swelling and hydrophilic capability, nutritional and visual functionality, supporting its suitability as stromal implants. Cytocompatibility distinguished by morphology and function of corneal epithelial, stromal, and endothelial cells on PNG lenticules suggested firm adhesion, over 90% viability, phenotypic maintenance instead of excessive keratocyte-myofibroblast transformation. In-vitro immune response analyzed by illumina RNA sequencing in human peripheral blood mononuclear cells indicated that PNG lenticules activated type-2 immunity, facilitating tissue regeneration and suppressing inflammation. In-vivo performance assessed using intrastromal keratoplasty (ISK) models in New Zealand white rabbits illustrated that implantation of PNG lenticules maintained stable optical pathway, induced controlled stromal bio-integration and regeneration, avoided complications such as stromal melt, interface scarring, etc., but exerted no adverse effects on the host. Postoperative follow-up examination on intraocular pressure, corneal sensitivity, and tear production remained unaffected by surgery up to 1-month post-implantation of PNG lenticules. DLP-bioprinted PNG lenticule is a bio-safe and functionally effective stromal implants with customizable physical dimensions, providing potential therapeutic strategies in correction of refractive errors.
Keyphrases
- cataract surgery
- bone marrow
- endothelial cells
- immune response
- high glucose
- adverse drug
- patient safety
- stem cells
- wound healing
- mental health
- high resolution
- physical activity
- patients undergoing
- signaling pathway
- oxidative stress
- staphylococcus aureus
- mass spectrometry
- toll like receptor
- risk assessment
- diabetic rats
- inflammatory response
- quality improvement
- combination therapy
- biofilm formation
- single cell
- dendritic cells
- solid phase extraction
- surgical site infection
- smoking cessation
- percutaneous coronary intervention