Research

1. Assembly of Interfacial Polyelectrolyte Complexation Fibers with Mineralization Gradient for Physiologically-inspired Ligament Regeneration.
Liu YC, Chen SH, Kuan CH, Chen SH, Huang WY, Chen HX, Wang TW*
Advanced Materials. 2024, 2314294  

介面聚電解質落合紡織技術展示了卓越的仿生性質和再生潛力，包含階層式結構和礦化梯度模擬韌帶微結構。同時，支架在循環拉伸測試中展現與原生韌帶組織相似的性能。與LARS和自體移植物相比，該支架在生物相容整合性、機械性能和再生潛力具有顯著優勢。 本研究成功結合治療因子與細胞治療，實現長期且持續的再生修復效果。本技術可推動醫材產業開發。針對韌帶與肌腱損傷、退化性疾病及其他肌骨骼組織修復，支架可根據患者進行個人化設計，並搭載不同治療因子以應對疾病需求。 本技術還可應用於人工神經、體外模型、手術縫線等領域。其製造成本可控，市場需求龐大，經濟效益顯著，有望成為生物醫學領域的重要突破，為患者和醫療產業帶來深遠影響。

• 國外專文報導： "Biomimetic De Novo Ligament Regeneration"  Advances in Engineering  https://advanceseng.com/biomimetic-de-novo-ligament-regeneration/

•  國內媒體報導；台灣新視野節目 (民視)  https://www.youtube.com/watch?v=9o4kLG9lvlE

•  2024 國科會未來科技獎 2024 The Tech Innovation Excellence Award (TIE Award), National Science and Technology Council, Taiwan

Significance: 

The inherent limitation in the healing capacity of ligaments, particularly intra-articular ligaments like the ACL, adds to the complexity of treatment. This work introduces a physiologically inspired strategy to develop a biomimetic ligament replacement that effectively mimics native ligament performance, thereby facilitating ligament regeneration. The intricate hierarchical structure closely mirrors the fiber arrangement observed in native ligaments, providing guidance for the regenerative process. The hydroxyapatite gradient distribution of mineralized constituents promotes the transition from soft to hard tissue and enhances the healing process at the ligament-to-bone interface. Custom-tailored viscoelastic properties are designed to mirror those inherent in native ligament, ensuring proper load-bearing capacity and stability. The introduction of stem cells and the delivery of growth factors facilitate the formation of functional ligamentous tissue. Through these advancements, this research improves injury outcomes, facilitates recovery, and provides a long-lasting, effective solution for ligament injuries.

Highlights of this research are:

• Ligament-like hierarchical architecture is developed to closely mimic the hierarchical fiber organization of ligaments and serve as a structural cue for de novo tissue generation.

• Enthesis-like hydroxyapatite gradient is incorporated to promote transition from soft to hard tissue and enhance ligament-to-bone interface healing.

• Biomimetic viscoelasticity is engineered to provide mechanical support like that of native ligamentous tissue under physiological conditions.

• Tissue-engineered strategies, including MSC inoculation and growth factor delivery, are included to improve the regenerative outcome.

2.  Hierarchical Assembly and Dynamic Reinforced Woven Biotextiles for Anisotropic and Viscoelastic Tendon Tissue Regeneration.
Chen HX, Chen SH, Chen SH, Liu YC, Wu CT, Chen JX, Wang TW* 
Carbohydrate Polymers 2026; 380: 125090

此研究發展出高度擬真的生物仿生肌腱，克服天然肌腱修復能力差，以及自體／同種異體移植與人工替代物常見的供應不足、免疫排斥、不良整合、長期疲勞鬆弛與再斷裂等問題。我們透過前瞻性的聚電解質絡合紡絲技術，調控纖維生成、排列、融合與採集，使其能承受人體高拉應力，並大幅降低疲勞與蠕變效應，並結合天然仿生纖維材料，自下而上精準組裝具階層微結構、高黏彈性、高機械強度、低蠕變量的「生物型肌腱組織」。本研究打造出符合天然肌腱微觀結構與力學需求、具備良好生物相容性與整合性的高性能替代植體。不僅適用於臨床肌腱重建，亦能依患者需求量身訂製，確保高拉強度與長期穩定性，避免疲勞或應力鬆弛，為肌腱組織修復提供創新且可行的再生醫學解決方案。

Significance:

Tendon regeneration is a well-recognized clinical challenge, primarily due to its limited healing capacity and the prolonged rehabilitation time required for functional recovery. This research study presents a bioinspired approach to developing a biomimetic tendon graft that effectively mimics the performance of native tendons, thereby facilitating tendon regeneration. The anisotropic architecture, resembling the native tendon's anatomical structure, is designed to correspond to the interfacial polyelectrolyte pattern. It offers exceptional programmability and encapsulation capabilities for arranging cells and growth factors, surpassing traditional spinning techniques. Additionally, customized twisting and weaving techniques are employed to refine the scaffold's mechanical properties and better approximate the characteristics of native tendon tissue. The dynamic culture system and the incorporation of tendon-specific growth factors work synergistically to enhance mechanical and chemical stimulation, promoting functional regenerative outcomes. Tailor-designed viscoelastic and anti-fatigue properties are created by silk fibroin sheathing to mirror those inherent in native tendons, ensuring proper daily activity requirements and stability in daily life. Through these advancements, this research aims to improve clinical outcomes, expedite patient recovery, and deliver a long-lasting, effective solution for tendon injuries.

Highlights of this research are:

• Advanced tissue engineering strategies with physiological and mechanical biomimicry, utilizing polysaccharides, are integrated to enhance tendon regeneration

• Chitosan- and γ-polyglutamic acid-incorporated IPC fibers with silk-fibroin coating enhance the creep recovery ratio and stress retention

• Hierarchical assembling replicates the fiber organization and orientation to form anisotropic tendon structures

• Tendon biomimicry exhibits viscoelasticity and anti-fatigue characteristics, highlighting its potential for sustained performance 

• IPC fibers that are collected, twisted, woven, and dynamically stretched fulfill clinically relevant requirements

3. Self-transforming Bioadhesive Patch with Topological and Ionic Crosslinking for Adaptive Mucoadhesion and Enhanced Wound Healing.
Liao SY, Hsu HA, Kuan CH, Yu LJ, Tu CY, Tsai CH, Liao YT, Wang TW*  
Advanced Healthcare Materials 2026:e04609.

口腔黏膜傷口為常見的臨床問題，其成因包含口腔外科手術、癌因性口腔黏膜炎、一般黏膜潰瘍及自體免疫疾病。口腔黏膜傷口的照護因口腔內的獨特環境面臨重大的臨床挑戰，包括潮濕、唾液的存在以及持續的機械摩擦均會影響並阻礙黏膜傷口的癒合。傳統的傷口敷料無法有效黏著於潮濕且動態的黏膜表面上，因此口腔黏膜傷口的照護一直為重要且未被滿足的臨床問題。為了滿足此一臨床需求，本研究開發了一種生物黏附性口腔內貼片（簡稱TRIM），其通過原位物理形態轉變機制附著在黏膜傷口表面。此外，口腔內貼片中複合入左旋麩醯胺酸，使該貼片系統不僅作為黏膜傷口敷料，同時可作為活性藥物載體，主動促進黏膜傷口癒合。TRIM表现出優於市售產品的機械強度和黏著強度，且能穩定持續的釋放麩醯胺酸，展現其作為局部黏膜藥物傳輸系統的能力。本研究之口腔內貼片符合ISO10993所定義的安全標準，於手術引發的口腔黏膜傷口動物實驗模型中，使用TRIM治療，傷口癒合速度顯著增長，且於組織染色中可觀察到發炎反應的降低，再上皮化、血管新生和肉芽組織的生長。

Significance: 

Oral mucosal wounds pose substantial clinical challenges due to the highly dynamic and moist environment of the oral cavity. Current strategies for managing oral mucosal wounds primarily focus on symptomatic relief through antiseptic mouthwashes and topical anesthetics. For example, commercially available oral wound dressings provide only temporary coverage with weak mucoadhesion and rapid detachment in the saliva-rich, high-shear stress environment of the oral cavity. Furthermore, these interventions fail to provide sustained mechanical protection, prolonged adhesion, or controlled drug delivery, limiting their overall therapeutic efficacy. To address this clinical issue, a topological and responsive ionic mucoadhesive (TRIM) patch is developed, integrating a bilayer structural design, topological adhesion, in-situ ionic crosslinking, and a dry-to-wet transformation mechanism to enhance adhesion, wound protection, and therapeutic effect in the oral environment.  Its dry-to-wet transformation ensures easy handling and precise application, while ion-mediated crosslinking reinforces adhesion strength and mechanical stability in wet environments. The dual-layer design enables controlled adhesion kinetics and degradation, optimizing retention and functionality in the oral cavity. Beyond adhesion, the patch also provides a biocompatible wound-healing interface, supporting re-epithelialization and tissue remodeling. These findings highlight the potential of integrating adaptive adhesion mechanisms with engineered bioadhesive materials, paving the way for future developments in mucosal drug delivery, surgical wound dressings, and dynamic tissue adhesive technologies.

Highlights of this research are:

• A mucoadhesive patch is developed by integrating topological adhesion, in situ ionic crosslinking, and a dry-to-wet transformation.

• TRIM patch provides rapid attachment in the saliva-rich, high-shear stress, moist environment of the oral cavity.

• This bilayer structure allows the adhesive layer to firmly adhere to the mucosa, while the backing layer gradually disintegrates, enabling sustained drug release without premature detachment.

• The critical roles of ion composition, hydration control, and pH responsiveness are demonstrated in optimizing bioadhesive performance.

• TRIM-Gln serves as both a mechanical barrier and a bioactive patch, leveraging the therapeutic benefits of L-glutamine to accelerate wound healing.

4.  Viscoelastic Hydrogel with Mechanomodulatory Tension Shielding and Time-Dependent Immunomodulatory Effects for Scarless Healing.
Kuan CH, Wang YN, Liao EF, Wang WH, Kung PJ, Huang WY, Chen SH, Chen SH, Hu JJ, Lin SJ, Wang TW*
Advanced Healthcare Materials 2025:e01954  

每年有數百萬人因手術、創傷或燒燙傷後的皮膚傷害而產生疤痕，這些傷勢會帶來嚴重的心理壓力和身生理上不良影響。 儘管在了解纖維化疤痕形成的原因（例如外部張力、發炎和過度膠原沉積）方面取得了進展，但實現無疤痕癒合仍然具有挑戰性。 受胎兒傷口癒合的啟發，這項研究開發出一種模仿胎兒細胞外基質特性的黏彈性水凝膠，以促進成人傷口的無疤痕癒合。我們所開發的新穎多功能水凝膠結合了張力屏蔽和免疫調節特性，通過運用生物力學、材料科學和免疫學的原則，為無疤痕癒合創造了較佳內在環境，在傷口修復上取得重大進展。 從未來的角度來看，這種黏彈性水凝膠亦可以作為植入式電極陣列與黏彈性組織介面的塗層，有效減少疤痕形成或纖維化包覆，避免植入裝置失效，並提供可靠的電訊號輸出。

Significance: 

ECM and tissues are viscoelastic, exhibiting time-dependent responses to loading or deformation, with stress relaxation behavior. Engineering the next generation of biomaterials with tunable viscoelasticity to direct cell behavior will advance in vivo regenerative therapies to address unmet clinical needs, such as scarless wound healing. To better understand the impact of ECM properties on wound healing, HAoxi-Alg viscoelastic hydrogels have been developed to investigate the role of mechanomodulatory tension-shielding and time-dependent immunomodulatory effects in regulating cell behavior.  The results revealed that matrix viscoelasticity regulates the wound healing process and can promote behaviors not observed with elastic hydrogels, such as decreasing the likelihood of fibroblast differentiation into myofibroblasts, fostering a positive feedback loop through M2 macrophage polarization, and preventing excessive collagen deposition. These findings have provided insights into cell-matrix interactions and how they differentially modulate mechano-sensitive molecular pathways during the wound-healing process. 

Highlights of this research are：

• Viscoelastic hydrogel effectively combines tension reduction and immunomodulation strategies to mitigate scarring

• Utilizing stress relaxation to dissipate traction forces, the hydrogel effectively addresses the fundamental cause of scarring.

• Secondary cross-linking enables spontaneous shrinkage of hydrogel, aiding wound closure and tension reduction.

• Polyelectrolyte complex nanoparticles preserve the bioactivity of IL-10, facilitate sustained release, and promote M2 macrophage polarization.

5. Immunomodulatory hydrogel orchestrates pro-regenerative response of macrophages and angiogenesis for chronic wound healing.
Kuan CH, Chang L, Ho CY, Tsai CH, Liu YC, Huang WY, Wang YN, Wang WH, Wang TW*  
Biomaterials 2025; 314: 122848

慢性傷口通常會使傷口停滯於發炎狀態，組織的長期發炎往往會阻礙慢性傷口的癒合，因此如何調節免疫刺激為治療此類慢性傷口的一大重點。此外，隨著癒合進程的推進，血管新生在血管化的開端和微血管網絡的建構上亦為不可或缺的一環。為了解決這個問題，我們成功開發一種雙層藻酸鹽水膠，在水膠中包裹一種搭載信號分子的聚電解複合奈米粒子（PCN），在時間上和空間上控制抗發炎細胞因子和血管生成生長因子的釋放，藉此模擬傷口的生理修復階段。作為傷口敷料來說，我們所設計的雙層水膠具有優異的生物相容性和良好的黏彈性質，而水膠的雙層結構也表現出截然不同的降解趨勢，可以去協調多種信號分子的釋放順序; 此外，PCN作為藥物載體也表現出與信號因子良好的結合力。而在水膠中搭載的IL-10可以透過激活Jak1/STAT3 pathway的方式來抑制促炎細胞因子/趨化因子的分泌，並調降免疫細胞發炎相關基因的表現量。我們透過該水膠系統的設計改變慢性傷口病理階段，有效朝向正常傷口之生理修復進程。

Significance: 

Chronic wounds exhibit physiological impairments, leading to prolonged inflammation, impaired angiogenesis, and hindered cellular migration. Patients with chronic wounds experience chronic pain, discomfort, functional impairment, and diminished quality of life, with mortality in severe cases. According to statistics, chronic wounds affected approximately 10 million individuals, underscoring their significant public health impact. Thus, developing effective strategies to reverse the impaired healing process to a normal physiologic state and accelerate wound healing is a clinically important need. This bioinspired hydrogel system, providing physiologic cues by mitigating inflammation and promoting angiogenesis, holds great promise for clinical translation. This research has great potential as a useful modality, a tool, and a practicable platform for chronic wound healing and other diseases, such as cardiovascular and ischemic diseases.

Highlights of this research are:

• Versatile hydrogel system enhances rapid re-epithelialization, immunomodulation, angiogenesis, and collagenesis.

• Polyelectrolyte complex nanoparticles (PCNs) for sustained signaling molecule release and bioactivity preservation.

• Unequipped PCNs sequester the accumulated pro-inflammatory chemokines from the wound milieu.

• Sequential release of IL-10, VEGF, and PDGF in a spatial and temporal manner mimics the natural wound-healing process.

• Successful modulation of inflammatory mediators and prominent inflammatory attenuation in endothelial cells for enhancing chronic wound healing.

6. Zwitterionic Modified and Freeze-thaw Reinforced Foldable Hydrogel as Intraocular Lens for Posterior Capsule Opacification Prevention.
Yang CJ, Huang WL, Yang Y, Kuan CH, Tseng CL, Wang TW* 
Biomaterials 2024; 309: 122593

此研究以天然高分子纖維素(cellulose)為基底，製作了一個可折疊的抗污人工水晶體水膠。透過反覆凍融循環的方式，能夠物理性地提升水膠的機械性質而不影響透光度！ 也不會導致化學交聯劑的殘留是一大賣點！ 本技術可應用於人工水晶體、導尿管、抗沾粘膜等需要抗細胞與蛋白貼附的材料表面。 原理： 水膠主要以天然高分子所組成，可降低發炎反應，並以反覆凍融循環方式控制冰晶排列與纖維走向來強化水膠強度與透光度。 一面由雙離子形成之水合層可避免細胞、細菌、蛋白等貼附，另一面則透過多巴胺可加強水膠與水晶體後囊組織之貼附性，避免周圍上皮細胞遷移至水膠附近而影響其透光度等性質。 另外，可折疊特性亦可縮小手術傷口的大小，提供手術便利性與安全性。

Significance: 

Cataract, the leading cause of blindness, refers to the clouding of the lens and has a significant impact on the daily lives of millions of people worldwide. This eye disease causes visual impairment, primarily characterized by blurred vision, halo formation, and light sensitivity. Although a wide variety of intraocular lenses have been developed and used clinically to replace the opacified crystalline lens, the posterior capsule opacification (PCO) remains a commonly encountered, vision-impairing postoperative condition.  In this study, we design and develop a foldable antifouling intraocular lens (IOL) implant to address this clinical unmet need. By leveraging the freeze-thaw approach, the hydrogel becomes highly transparent and acquires greater mechanical stiffness without the need for chemical crosslinking. The cytotoxicity issue of the crosslinking agent is also eliminated. The surface of the hydrogel is treated with zwitterionic modifications to achieve anti-adhesion properties, while the haptic and the peripheral region of the posterior surface are grafted with dopamine to promote posterior capsule attachment and impede lens epithelial cell (LEC) migration. We demonstrate that a PCO-preventing intraocular lens hydrogel with succinct, robust surface heterogeneity modifications achieves long-term therapeutic effects and improves postoperative visual experience.

Highlights of this research are:

• Successful development of a foldable, durable, biocompatible, and antifouling hydrogel, effectively inhibiting PCO.

• Application of a bio-friendly freeze-thaw technique to bolster the hydrogel’s mechanical stability without chemical crosslinking agents and maintain the transparency of IOL.

• Zwitterionic surface modifications on the cellulose hydrogel prevent protein adhesion and residual LECs proliferation.

• Targeted dopamine grafting on the haptic and the posterior optic periphery, ensuring robust IOL-to-posterior capsule adhesion, thus mitigating PCO risk.

7. Bioinspired Adhesive Nanofibrous Hydrogel Promotes Immune Infiltration through Effective Immuno-chemotherapy for Osteosarcoma Treatment.
Lee CH, Huang WY, Lee KY, Kuan CH, Wu TC, Sun JS, Wang TW* 
Chemical Engineering Journal 2024; 486 :150236

此研究開發一種黏性奈米纖維水膠 （功能類似OK繃），利用化學療法協同免疫療法進行聯合治療，化療藥物作為第一線治療，用來清除大部分的癌細胞；隨後免疫治療藉由誘導自身免疫反應將殘餘癌細胞清除，避免腫瘤轉移和復發。 研究結果證實該智慧型奈米纖維水膠能黏附於骨癌組織，並順序性釋放化學療法與免疫治療藥物，透過促進體內免疫反應與調控，有效提升抑制腫瘤的效果。

Significance: 

Osteosarcoma, the predominant primary malignant bone tumor, presents ongoing clinical challenges, notably in local recurrence and metastasis. In this study, we develop a bioinspired adhesive nanofibrous hydrogel, specifically formulated to concurrently deliver chemotherapeutic drugs and immune regulatory cytokines for osteosarcoma treatment. The nanofibrous hydrogel is composed of two layers: a bottom layer consisting of catechol-functionalized gelatin hydrogel and a top layer made up of hyaluronic acid (HA) / polycaprolactone (PCL) electrospun nanofiber matrix. This design induces sustained antitumor immune responses not only to eradicate residual tumor cells comprehensively but also to prevent tumor recurrence and metastasis, whilst concurrently minimizing the adverse effects. The in vivo results reveal that our nanofibrous hydrogel significantly enhances T-cell activation, facilitates lymphocyte infiltration into tumor tissue, and effectively suppresses tumor growth. This study presents a nanofibrous hydrogel drug delivery system embedded with glycosaminoglycan nanoparticles, offering a programmable approach to eradicating bone tumors. It leverages the synergistic capabilities of chemotherapy and immunotherapy, applied in a strategic chronological sequence.

Highlights of this research are:

• Adhesive nanofibrous hydrogel composites designed for osteosarcoma treatment, employing biomimetic principles.

• Preservation of bioactivity and extension of immunomodulators’ release through the polyelectrolyte complexation process.

• Implementation of temporally controlled degradation to facilitate the sequential and sustained release of immunogenic cytokines.

• Amplification of anti-tumor efficacy via a synergistic approach: initiating with chemotherapy-induced immunogenic cell death, followed by targeted immunotherapy

8. Hybrid Apoptotic Body Decorated Supramolecular Hydrogel System for Melanoma Cancer Immunoediting.
Huang WY, Liang NW, Kuan CH, Yu LJ, Wu TC, Chang CW, Wu TC, Liao YT, Wang TW*  
Chemical Engineering Journal 2025; 526 :171086

此研究提出一套具備多重免疫功能的混合胞外囊泡(Hybrid-EVs)平台，由腫瘤細胞誘導凋亡後產生的胞外囊泡（extracellular vesicles, EVs）為核心，複合FDA-approved 微脂體 (liposome nanoparticle, LNP)，形成Hybrid-EVs，研究概念所提出之Hybrid-EVs平台橫跨癌症免疫循環中多個關鍵環節，從抗原釋放、抗原呈現、免疫細胞募集、到T細胞效應恢復，建構一套具備前後連貫性與放大效果的免疫調控策略可有效強化體內抗腫瘤免疫反應，提升大腸癌治療效果。 透過腫瘤小鼠模型進行體內驗證，證明了本平台具備誘導系統性免疫活化與遠端腫瘤抑制之潛力，作為發展次世代癌症免疫治療或疫苗佐劑平台的重要基礎。 本平台兼具來源安全、功能可設計、模組可擴充等特性，除可作為次世代癌症疫苗佐劑外，亦具作為個人化免疫療法、聯合免疫/化療方案與細胞治療佐劑之潛力，為突破胞外囊泡應用限制、推進免疫療法臨床發展提供嶄新解方。

Significance: 

High recurrence and distant metastasis remain common in melanoma, even after conventional treatments including surgery and targeted therapy. Checkpoint blockade therapy shows promise, yet primary resistance and acquired relapse remain major limitations. In this research study, our immune cocktail therapy combines multiple mechanisms, including doxorubicin-induced tumor cell death, antigen delivery via Hy-ApoBDs, CX3CL1-mediated immune recruitment, and checkpoint blockade to comprehensively modulate the tumor immune microenvironment. This integrative approach addresses key clinical challenges in melanoma, including immune evasion, poor immune infiltration, and therapeutic resistance, and may offer a rational, synergistic strategy to improve treatment outcomes. Overall, our approach addresses three critical barriers in solid tumor immunotherapy: insufficient immune priming, persistent immune suppression, and poor systemic propagation. The work is particularly significant in its ability to reshape immune activation kinetics through spatiotemporal delivery, offering a feasible strategy to amplify host antitumor immunity with reduced collateral damage.

Highlights of this research are:

• Hybrid apoptotic bodies co-displaying “eat-me” and “find-me” signals enable precise immune cell recruitment and activation

• Supramolecular hydrogel addresses the cancer-immunity cycle and coordinates innate and adaptive immune events through sequential release of immunological cues.

• Bilateral immunomodulation amplifies systemic T cell responses and induces abscopal tumor regression

• Engineered vesicles enhance dendritic cell maturation, antigen cross-presentation, and Th1-polarized immunity

• Modular hydrogel-vesicle system adaptable for combinational immunotherapy across solid tumor types

• Multi-phase hydrogel delivery platform converts localized intervention into systemic innate–adaptive immunity, allowing strong translational potential in metastatic melanoma

9. Bioinspired Self-assembling Peptide Hydrogel with Proteoglycan-assisted Growth Factor Delivery for Therapeutic Angiogenesis.
Huang LC, Wang HC, Chen LH, Ho CY, Hsieh PH, Huang MY, Wu HC, Wang TW*
Theranostics 2019; 9(23): 7072-7087

當臨床上進行手術或處理意外創傷時，如何快速有效的達到止血以及傷口癒合的目的，到目前為止對於醫生來說仍然是個十分棘手的問題。另一方面，對於慢性潰瘍或長久無法癒合的傷口，如何提供創傷部位足夠的新生血管亦是促進此類型傷口修復重要且必需的步驟。在此研究中，我們開發出功能化的自聚合胜肽水膠，分別修飾上由兩段具不同功能的奈米胜肽序列(QLK 和LRK)。具有功能性序列QLK修飾的胜肽水膠，其經由轉谷氨酰胺酶交聯後，可在止血階段促使纖維蛋白之交聯強化，顯著提升水膠的機械性質；另一方面，藉由功能性序列LRK和蛋白聚醣硫酸乙酰肝素之間良好的結合親和力，此自聚合胜肽水膠能緩效釋放出搭載包覆於其中的血管内皮生長因子和肝細胞生長因子。該功能化的自組裝胜肽水膠能成為一具有新穎及前瞻性的生醫材料，應用於微創手術，並且對於缺血性疾病和慢性傷口的再生及修復達到良好的治療效果。

Significance: 

Critical challenges still exist in surgical theaters and emergency rooms to stop bleeding effectively and facilitate wound healing efficiently. In circumstances of tissue ischemia, it is essential to induce proper angiogenesis to provide adequate vascular supply to the injury site. In this study, we develop a hydrogel-based modality that serves as a more effective and safer hemostasis agent. The agent also has the ability to control the release of encapsulated therapeutic factors in an extended timeframe, to trigger neovascularization, and to restore a natural angiogenesis in our body. The design and strategies demonstrated in this study provide a potential hydrogel-based treatment for conditions such as surgical hemostasis, chronic ulcer, critical limb ischemia, ischemic stroke, and peripheral vascular disease. Furthermore, fSAP hydrogel can also serve as a suitable reservoir for the delivery of injectable stem cells or therapeutic biological molecules (genes/drugs), making it an attractive biomedical material with a wide range of potential applications.

Highlights of this research are:

• The mechanical property and the stability of fSAP hydrogel could be enhanced after endogenous transglutaminase enzyme mediation during coagulation process.

• The designer fSAPs are injectable with self-healing property and possess the ability to form hydrogel in situ; thus, becoming an effective hemostatic agent.

• The adoption of proteoglycan serves as protecting carrier for sequestering dual growth factors and maintains their release locally at injected site.

• The designer bioinspired fSAP hydrogel is an attractive and promising therapeutic modality for minimally-invasive surgery, ischemic tissue disorders and chronic wound healing.

10. Glycosaminoglycan-based Hybrid Hydrogel Encapsulated with Polyelectrolyte Complex Nanoparticles for Endogenous Stem Cell Regulation in Central Nervous System Regeneration.
Jian WH, Wang HC, Kuan CH, Chen MH, Wu HC, Sun JS, Wang TW*
Biomaterials 2018: 174; 17-30

神經幹細胞(NSCs)具有修復中樞神經系統受損的能力，為腦創傷、腦中風及腦退化性神經疾病開創極具潛力的治療策略。然而，神經幹細胞在腦創傷部位的再生能力不佳，這是由於創傷部位極劇的發炎反應、失去結構性的支持、以及缺乏營養因子的滋養，而限制了治療效果。腦部正常的細胞外間質(ECM)由多種物質組成，例如:透明質酸及蛋白聚醣，這些組成物提供了理想的胞外微環境，使生長因子、趨化因子及其它生物活性因子擁有良好的儲存空間，以及避免蛋白質受到蛋白質分解酶的降解，並在生物體內提供了促進NSCs增生及分化的適當條件。此研究結合了搭載兩種生長因子的複合奈米粒子及模仿腦細胞外基質結構的水膠，不僅可進行局部注射，更可穩定生長因子於生理環境下的生物活性。更進一步地，水膠所釋放帶有生長因子的複合奈米粒子不僅可促進內源性NSCs的化學趨向性及存活率，並提供幹細胞理想的增生及分化環境，在腦神經組織的再生及修復上達到良好的效用。

Significance: 

The significance of this research study is that brain injury, either by cerebrovascular or traumatic event, is a challenging issue in clinical settings. It typically causes neural damage that leads to neurological dysfunction, degeneration and irreversible damage to various degrees. To pass through the complex ex vivo processes and limitations of exogenous cell transplantation and to get effective stimulation on endogenous stem cell responses for regeneration, the glycosaminoglycan (GAG)-based nanohybrid hydrogel in this study is designed for delicate delivery of stromal-derived factor-1α and basic fibroblast factor to the injured brain, and for preserving their bioactivities through the inherent GAG-protein interactions. Applying this biomimic hydrogel to the stroke cavity in rats improves neuroregeneration and vascularization in peri-infarction tissue. These findings herein provide a promising alternative to drive the capabilities of endogenous neural stem cells for brain tissue regeneration with great potential. The strategies used in this study can be applied for tissue regeneration in other morbid conditions by recruitment of circulating stem/progenitor cells to the injured site or to deliver other GAG-binding growth factors such as bone morphogenetic protein, vascular endothelial growth factor, and platelet-derived growth factor for bone regeneration, chronic wound repair, angiogenesis for ischemia disease, etc.

Highlights of this research are:

• Awaken innate regenerative capabilities in brain tissue by biomimicry design

• Create appropriate microenvironment to promote body’s own regenerating capacity

• Enhance endogenous neural stem cells recruitment, survival, and proliferation from SVZ

• Protect and control the release of multiple growth factors by polyelectrolyte complex nanoparticles

• Establish photothrombotic ischemia (PTI) model in rat brain and provide therapeutic efficacy for stroke rescue

Research/Clinical Collaborators

• Dr. Chen-Hsiang Kuan, Division of Plastic Surgery, Department of Surgery, National Taiwan University Hospital, Taiwan

• Dr. Shih-Heng Chen, Division of Plastic Surgery, Department of Surgery, Chang Gung Memorial Hospital, Taiwan

• Dr. Chen-Chie Wang, Department of Orthopedic Surgery, Taipei Tzu Chi Hospital, Taiwan

• Dr. Tsung-Chiao Wu, , Department of Orthopedic Surgery, Taipei Tzu Chi Hospital, Taiwan

• Dr. Ming-Hong Chen, Department of Neurosurgery, Taipei Tzu Chi Hospital, Taiwan

• Dr. Huan-Chih Wang, Division of Neurosurgery, Department of Surgery, National Taiwan University Hospital, Taiwan

• Dr. Jui-Sheng Sun, Department of Orthopaedic Surgery, National Taiwan University Hospital, Taiwan

• Dr. Ming-Yuan Huang, Department of Emergency, Mackay Memorial Hospital, Taiwan