Cell-encapsulating Collagen-alginate Composite Device
細胞封裝膠原-海藻酸鹽複合裝置

Research Interests 研究興趣

An injectable cell-encapsulating collagen-alginate composite device for safe ocular drug delivery

一種用於安全眼部藥物輸送的可注射細胞封裝膠原-海藻酸鹽複合裝置

One obstacle in treating retinal disorders is the lack of an appropriate drug delivery system.  The existing approaches such as topical application (e.g. eye drops) and other conventional methods (e.g. oral, intravenous) limits the entrance of most drugs into retina.  Direct intraocular injection is problematic because of short half-life of the drugs and the chronic nature of degenerative retinal disorders; repeated injections are therefore obligatory, which is a burden as well as a safety issue to patients.  There arises an unmet need for better intraocular delivery of therapeutic molecules such that a consistent supply of the agents is available for a prolonged period of time.

治療視網膜疾病的一個障礙是缺乏合適的藥物輸送系統。現有的局部應用（例如滴眼藥水）和其他常規方法（例如口服，靜脈注射）限制了大多數藥物進入視網膜。由於藥物的半衰期短和退化性視網膜疾病的慢性性質，現有的方法是直接眼內注射 (甚至重複注射)，但這個方法對患者來說既是負擔又有安全問題，所以當前的眼內治療分子輸送存在未能滿足的需求。

​

Based on a cell-based delivery system in combination with encapsulated cell technology (ECT), we fabricated a collagen-alginate composite (CAC) gel using the naturally occurring collagen and alginate.  Collagen is a natural structural material present in the extracellular matrix and constitutes the greatest quantity of total proteins in the human body.  It is also one of the most extensively used extracellular matrix materials in neural tissue engineering.  Alginate is a natural linear anionic polysaccharide purified from brown algae.  As alginate is biologically inert, it is the most studied biomaterial for ECT.

使用天然存在的膠原蛋白和藻酸鹽，再結合細胞的輸送系統與封裝細胞技術 (ECT)，我們的團隊製造了膠原蛋白-藻酸鹽複合物 (CAC) 凝膠ECT裝置。膠原蛋白是存在於細胞外基質中的天然結構材料，是人體總蛋白質中含量最多的，也是神經組織工程中應用最廣泛的細胞外基質材料之一。藻酸鹽是從褐藻中提純的天然線性陰離子多醣。 由於藻酸鹽具有生物惰性，因此它是 ECT 研究最多的生物材料。

​

Our CAC ECT device is engineered to deliver glial-derived neurotrophic factor (GDNF), a member of the TGF-β superfamily and a potent neuroprotective agent effective in both central nervous system and peripheral nervous systems, including the retina.  The CAC ECT device is also equipped with the Tet-on inducible pro-caspase 8 mechanism.  This acted as an orally-inducible biosafety switch developed for safer drug delivery.  Our data showed that the CAC ECT device exhibited mechanical stability, good encapsulation power, cell viability support, multiplexed GDNF dosage.  Most importantly, CAC ECT device reduced photoreceptor apoptosis and retina function loss in Royal College of Surgeons rats, demonstrating therapeutic efficacy in retinal degeneration.  Both coated and non-coated CAC ECT devices can serve as well-controlled, sustained drug delivery platforms for treating posterior eye diseases without immunosuppression.  Our CAC ECT device offers an attractive, safe and well-controlled platform for treating various retinal diseases.

我們的CAC ECT裝置設計旨在提供神經膠質衍生的神經營養因子 (GDNF)，它是 TGF-β 超家族的一員，是一種有效的神經保護劑，對中樞神經系統和周圍神經系統（包括視網膜）均有效。 CAC ECT 裝置還配備了 Tet-on 誘導型 pro-caspase 8 機制，作為口服誘導型生物安全開關，用於更安全的藥物輸送。CAC ECT 裝置表現出機械穩定性、良好的封裝能力、細胞活力支持和多重 GDNF 劑量。最重要的是，CAC ECT 裝置減少了皇家外科學院大鼠的光感受器細胞凋亡和視網膜功能喪失，證明了它對視網膜變性的治療效果。塗層和非塗層 CAC ECT 裝置均可作為控制良好、持續的藥物輸送平台，用於治療無免疫抑制的後眼疾病。我們的 CAC ECT 設備為治療各種視網膜疾病提供了一個有吸引力、安全且控制良好的平台。