Biomimetic Vasculatures by 3D-Printed Porous Molds,Small

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Biomimetic Vasculatures by 3D-Printed Porous Molds
Small ( IF 13.0 ) Pub Date : 2022-07-22 , DOI: 10.1002/smll.202203426
Terry Ching _{1,

2,

3} , Jyothsna Vasudevan _{1,

3} , Shu-Yung Chang _{1,

2} , Hsih Yin Tan ₄ , Anupama Sargur Ranganath ₁ , Chwee Teck Lim _{3,

4,

5} , Javier G Fernandez ₁ , Jun Jie Ng _{6,

7,

8} , Yi-Chin Toh _{9,

10} , Michinao Hashimoto _{1,

2}

Affiliation

Pillar of Engineering Product Development, Singapore University of Technology and Design, 8 Somapah Rd, Singapore, 487372, Singapore.
Digital Manufacturing and Design Centre, Singapore University of Technology and Design, 8 Somapah Rd, Singapore, 487372, Singapore.
Department of Biomedical Engineering, National University of Singapore, 4 Engineering Drive 3, Singapore, 117583, Singapore.
Institute for Health Innovation and Technology, National University of Singapore, 14 Medical Drive #14-01, Singapore, 117599, Singapore.
Mechanobiology Institute, National University of Singapore, 5A Engineering Drive 1, Singapore, 117411, Singapore.
Division of Vascular and Endovascular Surgery, Department of Cardiac, Thoracic and Vascular Surgery, National University Heart Centre, 5 Lower Kent Ridge Rd, Singapore, 119074, Singapore.
Department of Surgery, Yong Loo Lin School of Medicine, National University of Singapore, 10 Medical Dr, Singapore, 117597, Singapore.
SingVaSC, Singapore Vascular Surgical Collaborative, 5 Lower Kent Ridge Rd, Singapore, 119074, Singapore.
School of Mechanical, Medical and Process Engineering, Queensland University of Technology, 2 George St, Brisbane City, QLD, 4000, Australia.
Centre for Biomedical Technologies, Queensland University of Technology, 60 Musk Avenue, Kelvin Grove, Brisbane, QLD, 4059, Australia.

Despite recent advances in biofabrication, recapitulating complex architectures of cell-laden vascular constructs remains challenging. To date, biofabricated vascular models have not yet realized four fundamental attributes of native vasculatures simultaneously: freestanding, branching, multilayered, and perfusable. In this work, a microfluidics-enabled molding technique combined with coaxial bioprinting to fabricate anatomically relevant, cell-laden vascular models consisting of hydrogels is developed. By using 3D porous molds of poly(ethylene glycol) diacrylate as casting templates that gradually release calcium ions as a crosslinking agent, freestanding, and perfusable vascular constructs of complex geometries are fabricated. The bioinks can be tailored to improve the compatibility with specific vascular cells and to tune the mechanical modulus mimicking native blood vessels. Crucially, the integration of relevant vascular cells (such as smooth muscle cells and endothelial cells) in a multilayer and biomimetic configuration is highlighted. It is also demonstrated that the fabricated freestanding vessels are amenable for testing percutaneous coronary interventions (i.e., drug-eluting balloons and stents) under physiological mechanical states such as stretching and bending. Overall, a versatile fabrication technique with multifaceted possibilities of generating biomimetic vascular models that can benefit future research in mechanistic understanding of cardiovascular diseases and the development of therapeutic interventions is introduced.

中文翻译：

3D 打印多孔模具的仿生脉管系统

尽管最近在生物制造方面取得了进展，但概括载有细胞的血管结构的复杂结构仍然具有挑战性。迄今为止，生物制造的血管模型尚未同时实现原生血管系统的四个基本属性：独立、分支、多层和可灌注。在这项工作中，开发了一种微流控成型技术与同轴生物打印相结合，以制造由水凝胶组成的解剖学相关、载有细胞的血管模型。通过使用聚（乙二醇）二丙烯酸酯的 3D 多孔模具作为铸造模板，逐渐释放钙离子作为交联剂，制造出具有复杂几何形状的独立式和可灌注血管结构。可以定制生物墨水以提高与特定血管细胞的相容性并调整模拟天然血管的机械模量。至关重要的是，强调了相关血管细胞（如平滑肌细胞和内皮细胞）在多层和仿生结构中的整合。它还表明，制造的独立血管适合在拉伸和弯曲等生理机械状态下测试经皮冠状动脉介入治疗（即药物洗脱球囊和支架）。总体而言，介绍了一种通用的制造技术，该技术具有生成仿生血管模型的多方面可能性，有助于未来对心血管疾病的机械理解和治疗干预的发展进行研究。至关重要的是，强调了相关血管细胞（如平滑肌细胞和内皮细胞）在多层和仿生结构中的整合。它还表明，制造的独立血管适合在拉伸和弯曲等生理机械状态下测试经皮冠状动脉介入治疗（即药物洗脱球囊和支架）。总体而言，介绍了一种通用的制造技术，该技术具有生成仿生血管模型的多方面可能性，有助于未来对心血管疾病的机械理解和治疗干预的发展进行研究。至关重要的是，强调了相关血管细胞（如平滑肌细胞和内皮细胞）在多层和仿生结构中的整合。它还表明，制造的独立血管适合在拉伸和弯曲等生理机械状态下测试经皮冠状动脉介入治疗（即药物洗脱球囊和支架）。总体而言，介绍了一种通用的制造技术，该技术具有生成仿生血管模型的多方面可能性，有助于未来对心血管疾病的机械理解和治疗干预的发展进行研究。它还表明，制造的独立血管适合在拉伸和弯曲等生理机械状态下测试经皮冠状动脉介入治疗（即药物洗脱球囊和支架）。总体而言，介绍了一种通用的制造技术，该技术具有生成仿生血管模型的多方面可能性，有助于未来对心血管疾病的机械理解和治疗干预的发展进行研究。它还表明，制造的独立血管适合在拉伸和弯曲等生理机械状态下测试经皮冠状动脉介入治疗（即药物洗脱球囊和支架）。总体而言，介绍了一种通用的制造技术，该技术具有生成仿生血管模型的多方面可能性，有助于未来对心血管疾病的机械理解和治疗干预的发展进行研究。

更新日期：2022-07-22

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