Silicone Hydrogel Stem Cell Lenses for Ocular Surface Retention
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Solution Overview
Problem
Current treatments for ocular graft-versus-host disease (oGVHD) are ineffective in preventing donor T cells from attacking the recipient's lacrimal duct and other eye tissues, and existing methods fail to maintain long-term retention of umbilical cord mesenchymal stem cells (UCMSCs) on the ocular surface.
Innovation Solution
Development of Mesenchymal Stem Cell-coating High Oxygen Permeable Hydrogel Lenses (MSCohi-O lenses) comprising a bowl-shaped silicone hydrogel carrier loaded with irradiated UCMSCs, which utilize a polymerized organosilicone monomer and hydrophilic monomer, ensuring UCMSCs do not proliferate and can stay on the ocular surface for extended periods, thereby treating oGVHD without interfering with allo-HSCT therapy.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If systemic administration of steroid hormones or immunosuppressants is used to treat oGVHD, then the therapeutic effect on donor's T cells is improved, but the drug concentration in the eye is insufficient and systemic side effects occur
Solution Approach 1:
The invention divides the treatment approach by placing UCMSCs directly on the ocular surface through contact lenses, separating the local ocular treatment from systemic administration. This allows targeted delivery of immunomodulatory cells to the eye without requiring systemic immunosuppression, thereby achieving local therapeutic effect while avoiding systemic side effects
Solution Approach 2:
UCMSCs serve as an intermediary substance that mediates the immunomodulatory effect locally at the ocular surface. These cells secrete cytokines and regulate immune responses directly where needed, replacing the need for systemic drug administration and achieving better drug concentration at the target site without systemic exposure
2Ease of operation
If topical immunosuppressants are used to treat oGVHD, then the local treatment is simplified, but the damage to eye tissues cannot be reversed
Solution Approach 1:
The invention changes the therapeutic parameter from单纯 immunosuppression to immunomodulation plus tissue repair. UCMSCs not only suppress immune responses but also secrete growth factors and cytokines that promote tissue regeneration and reverse corneal scarring, thereby maintaining topical application simplicity while adding the capability to reverse tissue damage
Solution Approach 2:
The contact lens combines UCMSCs with a hydrogel matrix to create a composite therapeutic device. This composite structure allows simultaneous delivery of living cells that can actively modulate immunity and repair tissues, going beyond the limitations of conventional topical immunosuppressants
3Reliability
If UCMSCs are applied topically to treat oGVHD, then the local immunomodulatory effect is improved, but the long-term retention of UCMSCs on the ocular surface is insufficient
Solution Approach 1:
The invention uses a contact lens as a flexible shell structure to承载 UCMSCs on the ocular surface. The lens provides physical support and retention for the cells, preventing them from being washed away by tears, thereby significantly extending the retention time of UCMSCs while maintaining their immunomodulatory function
Solution Approach 2:
The contact lens structure provides beforehand cushioning and protection for UCMSCs, creating a stable microenvironment that allows cells to survive and function longer on the ocular surface. This pre-established protective structure ensures prolonged contact between UCMSCs and target tissues
4Object-affected harmful factors
If conventional contact lenses are worn to protect the ocular surface, then the physical protection is provided, but the local inflammation is aggravated in the absence of tears
Solution Approach 1:
The contact lens with UCMSCs provides self-service by actively secreting immunomodulatory cytokines and growth factors that reduce inflammation and promote tissue repair. Rather than merely providing passive physical protection, the lens becomes an active therapeutic device that counteracts inflammation and supports ocular surface health
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
The MSCohi-O lenses effectively inhibit the attack of donor T cells on the lacrimal duct and other eye tissues by promoting Treg cell proliferation, inhibiting Th1 and Th17 cells, and secreting IDO to reduce inflammation, while maintaining safety by preventing systemic entry of UCMSCs, thus treating oGVHD without affecting the therapeutic effect of allo-HSCT.
Implementation Method 1
the bowl-shaped silicone hydrogel carrier is polymerized from an organosilicone monomer and a hydrophilic monomer under the action of a cross-linking agent and an initiator
Implementation Method 2
the organosilicone monomer is polymerized from a hydrogenated silicone oil and allyl methacrylate under the action of a polymerization inhibitor and a catalyst
Implementation Method 3
the UCMSCs are treated with irradiation
Data Source
AI summary
The disclosure provides lenses for treating ocular diseases, including a bowl-shaped silicone hydrogel carrier and umbilical cord mesenchymal stem cells loaded on the carrier; the bowl-shaped silicone hydrogel carrier is polymerized from an organosilicone monomer and a hydrophilic monomer under the action of a cross-linking agent and an initiator; the organosilicone monomer is polymerized from a hydrogenated silicone oil and allyl methacrylate under the action of a polymerization inhibitor and a catalyst; and the umbilical cord mesenchymal stem cells are treated with irradiation.