現今生醫材料快速發展，設計出能與人體協同作用、甚至模仿組織自主修復能力的材料，一直是科學追求的目標。徐善慧教授團隊多年來致力於開發智能型水膠(smart hydrogel)材料，其結合天然物質與高分子化學，成功創造出能夠自我修復、導電、可注射且具生物活性的材料，廣泛應用於皮膚傷口、關節修復與神經組織工程等多種臨床需求。

天然與合成的整合：聚胺酯與殼聚醣的動態交聯

這項創新技術結合了兩種截然不同但互補的材料：

• 水性聚胺酯(Polyurethane)：水相合成的可分解彈性高分子，力學性質穩定，彈性大。
• 殼聚醣(Chitosan)：一種天然多醣體，從蝦蟹殼中提取，具有良好的生物相容性、抗菌與免疫調節特性。

徐教授團隊透過動態鍵結技術，讓水性聚胺酯與殼聚醣之間能夠形成可逆的交聯網絡，造就一種新型的自癒合水膠。材料一旦受損，就能自動恢復結構，就像皮膚受傷後會自行癒合一樣。

團隊發展出來的水膠除了可在室溫與體溫下製備，製程更可依應用需求調整，在低溫製程下出高吸水彈性之形狀記憶冰膠材料，注射後可以在體內重建原本形狀與功能。這樣的材料特性在臨床應用上非常關鍵，例如注射進關節或神經損傷處時，能夠完整包覆且穩定停留。

導電型水膠：開創神經與感測應用

團隊進一步將導電奈米粒子(如polypyrrole、無機奈米粒子)加入水膠系統，創造出可導電、自我修復、拉伸彎曲的水膠材料。這種材料不僅應用於智能運動感測器，更進一步成功應用於神經修復的動物實驗(Chemistry of Materials 2020; Biomaterials, 2025)。

導電水膠在體內不僅能傳導生物電訊號，更能穩定細胞狀態、抑制發炎反應、促進神經元生長。這讓水膠不再只是被動的支架材料，而是成為能主動協助細胞修復的生物活性醫材。

自癒合水膠與針灸：跨界整合再生理論

在另一項創新整合應用中，團隊將自癒合水膠結合幹細胞與傳統針灸療法，應用於糖尿病大鼠的慢性傷口修復。實驗結果顯示，三者搭配能顯著促進皮膚癒合。徐教授團隊並提出了「鐵軌與枕木理論」：自癒合水膠與幹細胞如同「枕木」，提供組織修復所需的結構與生物信號；針灸則像「鐵軌」，引導免疫細胞與內源幹細胞遷移至傷口處(Biomaterials 2021)。

這項理論指出，材料與療法可以在免疫調控與組織重建上互補協同，為慢性傷口與再生醫學帶來嶄新思維。

組織工程的進一步突破：3D列印與形狀記憶功能

在組織工程領域，水膠被設計為多層冷凍凝膠結構，每層搭載不同藥物與孔洞，可透過注射後快速恢復三維結構，應用於兔子膝蓋軟骨與骨頭同時修復的動物模型上，成效顯著(Advanced Healthcare Materials 2024)。

更進一步，團隊結合形狀記憶編程，使水膠能夠先壓縮進注射器中，注射後迅速恢復複雜形狀，解決過去大型支架難以注射與植入的瓶頸(ACS Applied Materials & Interfaces 2021, 2022)。

帕金森氏症治療的里程碑

2022年起，團隊將微導電水膠應用於巴金森病大鼠模型。研究顯示，即便不搭配任何藥物，這種材料也能減緩神經退化、改善運動功能(Chemical Engineering Journal 2022)。

團隊接著設計出富含單寧酸的交聯結構，發現其治療效果甚至優於藥物載體水膠(Biomaterials Research 2023)。最新研究則開發出由聚胺酯與多巴胺修飾殼聚醣組成的微導電核殼型水膠，在巴金森動物實驗中取得最佳療效(Biomaterials 2025)。

徐教授團隊的研究成功整合了合成材料的可設計性與天然素材的生物活性，並結合化學、材料、生醫、針灸與3D列印等跨領域技術，創造出多功能、可注射、能自我修復的智慧材料。這不僅在國際期刊上屢獲封面與高度引用，也具體展現了其臨床應用與產業轉譯的潛力，為未來個人化精準醫療與再生醫學開啟新的篇章。

（105年度TBF學術講座、台大高分子科學與工程學研究所　徐善慧教授）

Injectable Self-Healing Hydrogels: Innovation from Wound Healing to Neural Tissue Engineering Regeneration

In the rapidly evolving field of biomedical materials, designing substances that can synergistically interact with the human body, and even mimic tissue self-repair mechanisms, remains a significant scientific pursuit. Professor Shan-hui Hsu's research team has been dedicated for many years to developing smart hydrogels by combining natural substances with polymer chemistry. They have successfully created self-healing, conductive, injectable, and bioactive hydrogels, which have been broadly applied in various clinical needs, including skin wound healing, joint repair, and neural tissue engineering.

Bridging Synthetic and Natural: PU-Chitosan Dynamic Crosslinking

At the core of this innovation is a unique integration of two complementary materials:

• Polyurethane (PU): A versatile synthetic polymer known for its mechanical strength and flexibility.
• Chitosan: A biopolymer derived from crustacean shells, offering biodegradability, biocompatibility, and anti-inflammatory properties.

Professor Hsu's research team utilized dynamic bonding technology to establish a reversible crosslinked network between waterborne polyurethane and chitosan, developing a novel self-healing hydrogel. When damaged, the material can autonomously restore its structure, much like how skin heals naturally after injury.

In addition, the hydrogel developed by the team can be prepared at room and body temperature, with its fabrication process adjustable according to application needs. Under low-temperature conditions, a highly water-absorbent and elastic shape-memory cryogel can be produced, capable of reconstructing its original shape and function after injection into the body. This property is crucial for clinical applications, such as providing stable and complete coverage when injected into joint or nerve injury sites.

Electrically Conductive Hydrogels for Neural Repair and motion sensing

The team further integrated conductive nanoparticles (such as polypyrrole and inorganic nanoparticles) into the hydrogel system, creating a conductive, self-healing, and stretchable hydrogel material. This advanced material has been successfully employed not only in intelligent motion sensors but also demonstrated effective nerve regeneration in animal studies (Chemistry of Materials 2020; Biomaterials, 2025).

When implanted into the body, the conductive hydrogel not only facilitates transmission of bioelectric signals but also stabilizes cellular conditions, reduces inflammatory responses, and promotes neuronal growth. As a result, the hydrogel transcends its role as a passive structural scaffold and emerges as a bioactive medical device that actively supports cellular repair and regeneration.

Merging Acupuncture and Biomaterials: The "Rail and Sleeper" Concept

In another innovative integrative application, the team combined self-healing hydrogels with stem cells and traditional acupuncture therapy to treat chronic wounds in diabetic rats. Experimental results demonstrated that the synergistic use of these three approaches significantly accelerated skin wound healing. Professor Hsu’s team further proposed the "Rail and Sleeper" theory, suggesting that the self-healing hydrogel and stem cells act as "sleepers," providing essential structural support and biological signals for tissue regeneration, while acupuncture serves as the "rails," guiding immune cells and endogenous stem cells to migrate toward the wound site (Biomaterials, 2021).

This theory highlights how materials and therapies can complement each other in immune regulation and tissue reconstruction, offering novel perspectives for chronic wound healing and regenerative medicine.

Engineering Cartilage with 3D Printing and Shape Memory

In the field of tissue engineering, hydrogels have been designed as multilayer cryogel structures, with each layer loaded with distinct therapeutic agents and pore architectures. These hydrogels can rapidly regain their three-dimensional structure following injection, demonstrating significant efficacy in simultaneous cartilage and bone regeneration in rabbit knee joint models (Advanced Healthcare Materials, 2024).

Moreover, the team incorporated shape-memory programming, enabling the hydrogel scaffolds to be compressed into syringes and quickly restore their complex shapes post-injection. This innovative approach addresses the longstanding challenge of delivering and implanting large-scale scaffolds via minimally invasive injection techniques (ACS Applied Materials & Interfaces, 2021, 2022).

A Milestone in Treating Parkinson’s Disease

Since 2022, the team has applied micro-conductive hydrogels in Parkinson’s disease rat models. Studies demonstrated that even without any drug loading, this material could slow neurodegeneration and improve motor function (Chemical Engineering Journal, 2022).

Subsequently, the team developed a tannic acid-rich crosslinked structure, discovering that its therapeutic effect surpassed that of conventional drug-loaded hydrogels (Biomaterials Research, 2023). The latest research introduced a micro-conductive core-shell hydrogel composed of polyurethane and dopamine-modified chitosan, achieving optimal therapeutic outcomes in Parkinson’s animal experiments (Biomaterials, 2025).

Professor Hsu’s team has successfully integrated the design flexibility of synthetic materials with the bioactivity of natural substances, combining chemistry, materials science, biomedicine, acupuncture, and 3D printing in a multidisciplinary approach to create multifunctional, injectable, self-healing smart materials. This work has not only garnered multiple journal covers and high citations internationally but also vividly demonstrates strong potential for clinical application and industrial translation, opening new avenues for personalized precision medicine and regenerative therapies.

(2016 TBF Chair in Biotechnology, Professor Shan-Hui Hsu)