An injectable thermoresponsive-hydrogel for lamellar keratoplasty: In-situ releases celastrol and hampers corneal scars.

Corneal stromal fibrosis is a common cause of visual impairment resulting from corneal injury, inflammation and surgery. Therefore, there is an unmet need for inhibiting corneal stromal fibrosis. However, bioavailability of topical eye drops is very low due to the tear and corneal barriers. In situ delivery offers a unique alternative to improve efficacy and minimize systemic toxicity. Herein, a drug delivery platform based on thermoresponsive injectable hydrogel/nano-micelles composite with in situ drug-controlled release and long-acting features is developed to prevent corneal scarring and reduce corneal stromal fibrosis in lamellar keratoplasty. The in-situ gelation hydrogels enabled direct delivery of celastrol to the corneal stroma. In vivo evaluation with a rabbit anterior lamellar keratoplasty model showed that hydrogel/micelles platform could effectively inhibit corneal stromal fibrosis. This strategy achieves controlled and prolonged release of celastrol in the corneal stroma of rabbit. Following a single corneal interlamellar injection, celastrol effectively alleviated fibrosis via mTORC1 signal promoting autophagy and inhibiting TGF-ß1/Smad2/3 signaling pathway. Overall, this strategy demonstrates promise for the clinical application of celastrol in preventing corneal scarring and reducing corneal stromal fibrosis post-lamellar keratoplasty, highlighting the potential benefits of targeted drug delivery systems in ocular therapeutics.

Effects of different scaffolds on rat adipose tissue derived stroma cells.

BACKGROUND: Adipose tissue derived stroma cells (ASC's) offer for many advantages for tissue engineering strategies over mesenchymal stroma cells from other sources and ideal carrier materials have to be identified for them. The aim of this study was to demonstrate and to compare the effects of three clinically established biomaterials on proliferation and metabolic activity of rat ASC's in vitro. MATERIALS AND METHODS: Rat adipose tissue derived stroma cells (ASC's) were isolated and differentiated into distinct lineages proved by lineage specific staining and gene expression analysis (RT-PCR). The biomaterials Bio-Gide(®), Tutodent(®) Membrane and Belotero(®) Soft were tested with rat ASC's for their biocompatibility using scanning electron microscopy (SEM), cell vitality staining, cytotoxicity and proliferation tests (LDH, MTT, BrdU, WST-1). RESULTS: The collagen membrane Bio-Gide(®) resulted in a significantly higher viability and proliferation (WST-1, BrdU) compared to Tutodent(®) Membrane. No significant difference was determined in the LDH and MTT test. The hyaluronic acid gel Belotero(®) Soft showed no cytotoxicity (LDH, FDA/PI) and had no negative effects on metabolic activity (WST-1, MTT) or cell proliferation (BrdU) of ASC's. CONCLUSION: Our results indicate Bio-Gide(®) and Belotero(®) Soft as preferable carrier materials for ASC's. For the further establishment of ASC's-based treatment strategies, in vivo investigations on the tissue regeneration potential of these cell-biomaterial scaffolds should follow.