专栏名称: EngineeringForLife

聚焦并解读再生医学、组织工程、生物材料等领域的最新进展，为医工交叉领域的研究人员提供交流合作平台。

杨华勇院士领衔，31家机构55位作者74页大综述：中国在组织/器官再生3D打印领域的科研进展

EngineeringForLife · 公众号 · · 2025-03-07 00:00

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在医疗技术革命的浪潮中，生物3D打印正突破传统治疗范式，开启从手术切除到再生医学的颠覆性变革。 Bio-Design and Manufacturing（BDM） 期刊全新推出「 BDM学科地理前沿 」栏目，以国家为维度深度解析医工交叉领域创新版图，以一篇文章透视一国科研实力。

继日本、以色列、英国&爱尔兰之后，本栏目第四篇聚焦中国，由 杨华勇院士 与贺永教授领衔， 31 所高校机构、55位学者历时一年合作撰写而成的主题综述 3D printing for tissue/organ regeneration in China 上线。

（本栏目往期推送见文末链接）

引 用本文 （点击最下方阅读原文可下载PDF）

He C, He J, Wu C, et al., 2025. 3D printing for tissue/organ regeneration in China. Bio-des Manuf (Early Access). https://doi.org/10.1631/bdm.2400309

硬核拆解：3D生物打印的核心原理和演化轨迹

面向组织再生的生物3D打印主要围绕可降解材料和载细胞生物墨水展开。其过程可划分为四个阶段。

第一阶段 ：制备无细胞生物支架，利用物理化学因素加速组织修复

第二阶段 ：制造载细胞支架，以更准确地模拟生物活动和功能

第三阶段 ：实现特定生物组织的部分重建，并恢复其基本生物功能

第四阶段 ：器官重建并实现其完整的生物功能，例如人造心脏和肝脏等

此外，这一技术演变还涵盖一个 辅助阶段 ：即利用器官芯片或类器官的体外组织模型来模拟生物功能，从而促进对生理过程的更深入理解并优化组织再生策略。

图1 面向组织再生的生物3D打印演变过程

当前，我们正处于从第二阶段向第三阶段的过渡时期，这一飞跃性的进展要求对生物组织的多功能性、高精度以及自组织特性进行深入的探索与研究。人体的各种组织/器官各自具备独特的生物学功能与生理特性，例如，肌肉骨骼系统强调组织的强度与灵活性，神经系统则优先考虑电信号的准确与快速传输，而循环系统则侧重于密封性与通畅性。因此，在追求统一的顶层设计之外，我们还需要针对特定组织的独特特征进行个性化的设计，以满足其特定的需求。这要求临床医生、工程师以及材料科学家等整个研究链条上的各方密切合作，共同推动生物打印的发展。

需要明确的是，本综述旨在探讨3D打印在组织再生领域的进展。因此涵盖的范围仅限于能够促进组织再生的可降解材料以及载细胞生物墨水的3D打印。不可降解材料则不纳入本综述的讨论范畴。

前沿洞见：如何跨越「可移植器官制造」的复杂挑战

从组织工程到器官工程：

在自然组织中，其复杂的结构特征、生化信号的精确传递以及细胞群系之间的密切协作共同驱动了生物组织的自发整合，从而有效地执行了各种生命活动。这种复杂性使得在体外重建具有完整功能性的生物组织/器官成为一项极具挑战性的任务。目前，组织工程的研究主要集中在组织修复阶段，即通过向体内植入细胞外基质和/或细胞来刺激周围组织的再生和修复。然而，这些植入的组织工程支架通常仅具备有限的生物功能，主要依赖于其物理和化学特性，如表面结构和生长因子，来诱导周围细胞的生长、分化和迁移。

在追求制造“可移植器官”的过程中，我们面临着三个核心挑战： 精确制造、稳定移植以及长期存活 。首先，自然生物经过优化，能以最小消耗实现最大效益。当前3D生物打印在模拟仿生结构上有局限，尤其在材料成分、多层结构和几何形状的精确复制方面。其次，软组织重建面临固定和缝合挑战，需要平衡整体韧性和局部柔软性。最后，神经血管化对3D打印人造组织的长期存活至关重要，多级血管网络系统可提供必要营养和氧气，防止细胞凋亡，促进长期存活。神经调控机制可优化再生微环境，在促进组织再生与恢复中也扮演着不可或缺的角色。神经血管化是组织的基本生理需求，也是提升人造组织的整体性能与功能恢复效果的关键因素。

图2 可移植器官制造面临的挑战

从科学研究到临床应用：

临床产品直接影响患者健康和生命安全。因此，对安全性和有效性进行严格的监管至关重要。生物3D打印技术尽管科研广泛，但临床应用仍很少。一方面，临床转化研究还处于起步阶段；另一方面，政府部门也需要建立系统全面的监管和评估体系。3D打印产品在临床治疗应用中大致可分为两类：医疗器械与药品。医疗器械主要通过物理手段或辅助功能实现治疗目的，其作用机制不依赖于药理学、免疫学或代谢作用，而药品则旨在调节人体的生理功能。目前，市场上大多数的3D打印产品均属于医疗器械范畴，其临床应用需获得医疗器械注册证书。若3D打印产品中包含药物成分，如药物输送系统，则可能被视为药物或药械组合产品，并需要取得药品注册证书。相较于医疗器械，药品的研究、开发和生产过程更为复杂，对技术和设备的要求也更为严苛。特别是当3D打印产品涉及生物制剂（例如细胞、抗体、疫苗等）时，其管理需基于生物制剂的特定性质（如生物活性、免疫原性等）进行，因此，相关的临床试验过程可能会更加复杂和严格。

在中国，当前批准用于医疗3D打印的材料主要局限于钛、钽等无机不可降解材料。这类材料惰性强，监管审批相对简易。然而，这类材料主要通过机械嵌合的方式与组织结合，但并不牢固，且容易引发炎症、过敏等不良反应。 因此，未来的发展趋势将倾向于探索和开发面向组织再生的可降解材料。 尽管研究者们期望放宽监管政策以加速研究进程，但从监管角度而言，必须全面评估可降解人工植入物在体内的降解过程、代谢产物以及与宿主组织的相互作用，才能确保全生命周期行为的安全性。因此对于从研究到临床应用的转化过程，采取多阶段、渐进式的开发策略可能更为实用。例如，在3D打印医疗产品的生产中，可以优先考虑那些已经广泛应用于临床或仅需简单修改即可使用的材料。然而，从长远的角度来看，可降解材料、载药材料以及载生物制剂材料将成为未来研究的重点领域，对于推动医疗3D打印技术的发展具有重要意义。

图3 3D打印医疗器械监管中的全过程质量控制和全生命周期风险管理

中国智慧：中国在该领域的研究布局和创新成果

中国研究团队在3D生物打印技术方面取得了显著进展。在 打印材料 方面，推进了光固化墨水的标准化，开发了用于3D打印的可降解骨材料，多功能甘油水凝胶以及热固性弹性体等新型打印材料，为生物医学工程领域提供了更安全、更高效的材料解决方案。在 打印工艺 方面，研究工作主要聚焦在两条核心技术路径上：光固化打印和挤出式打印。光固化打印在高精度和多材料生物打印方面取得了显著进展，为复杂生物结构的精确构建开辟了新途径。同时，挤出式打印在优化打印窗口和实现高细胞密度打印方面也取得了重大进展，进一步增强了生物打印的功能性。在 打印方法 的探索中，研究团队对体积打印、微纳打印、嵌入式打印、梯度打印、压电材料打印和太空打印等一系列关键技术进行了深入研究。不仅扩大了3D生物打印的应用范围，还为未来的生物医学研究和临床应用提供了更多的可能性。此外，中国的研究团队也致力于开发器官芯片和类器官技术，旨在通过高度仿生的生理环境模拟来加速疾病建模、药物筛选和再生医学研究。

图4 生物3D打印技术进展

在组织再生策略的探索中，中国团队的研究内容涵盖了人体多个主要生理系统。其中， 骨骼肌肉系统 最受关注，包括生物陶瓷支架、多细胞支架、组织工程化骨骼、骨-软骨再生以及骨骼肌重建等方面。其次是 循环系统 ，主要研究重点包括人工血管、多级血管构建、功能化血管结构以及干细胞打印等。接下来是 神经系统 ，研究内容包括神经再生和脊髓损伤修复。 呼吸系统 研究主要集中在生物工程气管方面，而 生殖系统 则涉及海绵体组织修复。尽管 免疫系统 和消化系统方面的研究也存在，但相对不那么广泛，尚未触及核心功能，仅分别包括皮肤修复和血管化肝脏组织构建。 值得注意的是，泌尿系统和内分泌系统仍未得到探索，相关领域的研究潜力巨大，有望成为未来科研探索的“蓝海”区域。

本综述总结了近30个中国研究团队的研究进展，全方位地展示了3D打印在再生医学领域的前沿动态，鉴于篇幅所限，这里仅节选三项工作进行介绍。欢迎阅读本综述的英文全文版，了解更全面的研究进展。

图5 组织修复策略进展

工作1. 西安交通大学贺健康教授团队：生物可降解植入物的临床应用

生物降解植入物在组织工程中至关重要，作为组织再生的临时支撑，有望成为下一代临床医疗植入物。贺建康教授团队在增材制造个性化支架方面取得显著进展，尤其在软组织工程领域。他们优化了制造技术，制造出具有精确控制结构的生物降解支架，植入后能很好适应缺损区域，促进细胞增殖和分化。团队还解决了支架机械性能模仿天然组织的难题，并在乳房组织重建和气管修复中显示良好效果。与空军军医大学西京医院合作，开展了 全球首个定制化柔性生物降解乳房植入物的临床试验 ，31例病例显示植入物能有效与宿主组织整合并支持组织生长。还与唐都医院合作，提出了生物降解气道夹板的气管悬吊术， 已完成22例临床应用 ，均表现良好。这些临床试验获得显著认可，凸显了增材制造生物降解植入物在临床应用中的广阔潜力。

图6 可降解植入物的临床应用

工作2. 上交九院郝永强主任团队：骨/软骨修复的临床应用

骨/软骨缺损修复是骨科亟待解决的问题。相比传统植入材料，生物3D打印的个性化活性骨/软骨具有生物活性、骨/软骨诱导性及个性化设计等优势，临床应用前景广阔。郝永强主任团队致力于探索生物3D打印在此领域的应用，旨在实现有效且安全的治疗，并推动该技术从实验室走向临床实践。团队研发了多层生长因子复合支架，具有高精度和优异性能。他们还开发了负载骨髓间充质干细胞的复合支架，并设计制造了模仿天然骨和软骨组织的三层支架，实现了软骨和软骨下骨的同步再生。利用计算机辅助设计和制造技术，构建了类山羊股骨头的双相支架，实现了软骨和骨的整合结构。此外，团队还探索了利用工程化外泌体进行软骨修复和骨关节炎治疗的可行性。针对生物打印在骨缺损修复中的挑战，团队创建了具有快速内部血管化能力和持续骨诱导生物活性的分级多孔海绵状支架。他们还将富血小板血浆纳入系统，创建了活性骨修复支架，显著促进了血管长入和骨再生。团队首次在临床上应用了基于患者富血小板血浆的生物墨水与复合支架，用于修复和重建患者骨缺损，这是 全球首个相关临床应用案例 ，对未来骨科再生医学的发展具有重要指导意义。

图7 骨/软骨修复的临床应用

工作3. 浙江大学贺永教授团队：可移植气管制造

浙江大学贺永教授团队长期致力于大尺寸活性结构的体外制造研究。针对打印的大尺寸组织血供困难，细胞难以长期存活的难题，团队提出同轴生物3D打印方法，实现含多级血管网络结缔组织的高效构建。针对打印组织的强度低，难以满足临床需求的难题，团队提出生物混凝土设计方案，能够快速有效提升打印组织强度。同时，为提高打印精度和稳定性，团队建立了光固化生物墨水成形理论体系和评价指标，致力于推动生物墨水标准化，并研发了高精度、多材料打印装备。与上海市肺科医院陈昶教授团队合作，实现了长段活性气管的整体制造，证明了工程化制造的器官能够移植并长期存活。

图8 可移植气管制造

展望

突破时空的束缚，一直是人类追求的伟大梦想。在空间维度上，我们渴望深入探索宇宙的奥秘，实现星际迁徙的宏伟目标；而在时间维度上，我们则期盼能够延长生命的旅程，替换衰老的器官。事实上，在生物3D打印发展的早期阶段，人们曾畅想利用这一技术来制造可移植器官。然而，随着研究的深入，科学家们逐渐意识到，创造可移植器官的任务异常艰巨，故而“Organ Printing”的话题自2010年后就逐渐淡出了公众的视野。但近年来，随着3D打印技术的快速发展，我们认为： 是时候重新审视可移植器官制造这一话题了 。尽管道路仍然漫长且充满挑战，但这一目标已经不再是纯粹的科幻场景。

图9 器官工程：从形似到神似

为迈向这一目标，我们首先要关注的是： 如何实现更仿生的设计、更精确的打印以及更活性的墨水 。鉴于当前制造能力的局限性，仿生设计需要与工程实施能力相匹配；同时，对更高层次仿生学的追求也将不断推动制造技术的进步，实现更精准的打印效果。此外，作为整个技术体系的基石，生物墨水的性能亦需持续优化，未来研究应聚焦于如何结合人工智能手段，加速生物墨水的迭代，从而设计出匹配不同组织器官发育过程的智能响应型生物墨水。

在器官再造的基础研究中，神经化及血管化的成功构建是一个关键节点 ，它对于保障大尺寸工程组织的活性至关重要，也是生物组织功能化的基本前提。然而，自然组织内部的毛细血管网络以及神经末梢通常为微米尺度，而器官的整体尺寸要达到分米及以上尺度，这一由微观至宏观的跨尺度精确构造过程，对制造技术提出了极高的要求。

在3D打印的产业应用路径上，服务于细胞治疗将成为未来的聚焦重点 。当前，干细胞治疗主要通过直接注射细胞或细胞微球，但这种方式所呈现的细胞状态与生物体内的真实环境存在较大差异。相比之下，利用生物支架作为载体进行干细胞精准递送，并通过结构设计引导并调控细胞行为，能够促使细胞形成更接近真实状态的“迷你组织”。这一策略有望实现从细胞治疗向“迷你组织”治疗的范式转变，为临床治疗提供新的视角与路径。

撰写团队 ：西安交通大学贺健康教授；中国科学院吴成铁研究员、阮长顺研究员、顾奇研究员、白硕研究员；上交九院郝永强主任；哈尔滨工业大学吴洋教授；湖南大学韩晓筱教授；清华大学欧阳礼亮教授、熊卓教授、温鹏教授、庞媛研究员；广州医科大学谢茂彬教授；宁波大学邵磊研究员；太原理工大学聂晶教授；中南大学帅词俊教授；四川大学周长春研究员；香港理工大学赵昕教授；华南理工大学施雪涛教授；东华大学游正伟教授；西北工业大学汪焰恩教授。浙江大学尹俊研究员、周竑钊研究员、马梁教授、俞梦飞研究员、傅佳寅研究员、贺永教授、杨华勇院士。

阅读原文：https://doi.org/10.1631/bdm.2400309，与中国顶尖实验室同步前沿动态。

「BDM学科地理前沿」 栏目往期推送

1. 日本： 【封面文章】浙大机械韩冬等 | 日本生物制造前沿研究-2018-2023

Cao Q, Zhang Y, Deng R, et al., 2023 . Biomanufacturing in Japan: frontier research from 2018 to 2023. Bio-des Manuf 6(6):617–645. https://doi.org/10.1007/s42242-023-00261-3

2. 以色列： 浙大机械陶凯等 | 创新引领发展：以色列生物3D打印一瞥

Cao Q, Zhang Y, Deng R, et al., 2023 . Biomanufacturing in Japan: frontier research from 2018 to 2023. Bio-des Manuf 6(6):617–645. https://doi.org/10.1007/s42242-023-00261-3

‍ 3. 英国&爱尔兰： 【封面文章】剑桥Shery Huang和布里斯托James Armstrong等 | 生物制造领域学科前沿——爱尔兰和英国篇

Murphy JF, Lavelle M, Asciak L, et al., 2024. Biofabrication and biomanufacturing in Ireland and the UK. Bio-des Manuf 7(6):825-856. https://doi.org/10.1007/ s42242-024-00316-z

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关于本刊

Bio-Design and Manufacturing （中文名《生物设计与制造》） ，简称BDM，是浙江大学主办的专业英文双月刊，主编杨华勇院士、崔占峰院士，2018年新创，2019年被SCI-E等库检索，2023年起改为双月刊，年末升入《2023年中国科学院文献情报中心期刊分区表》医学一区，2024年公布的最新影响因子为8.1，位列JCR的Q1区，13/122。

初审迅速 ：初审快速退稿，不影响作者投其它期刊。

审稿速度快 ：学科编辑24小时初审决定投稿是否进入同行评议阶段；平均评审录用周期约40天；文章录用后及时在线SpringerLink，一般两周左右即被SCI-E检索。

收稿方向 ：先进制造（3D打印及生物处理工程等）、生物墨水与配方、组织与器官工程、医学与诊断装置、生物产品设计、仿生设计与制造等。

文章类型 ：Research Article, Review, Short Paper (包括Editorial, Perspective, Letter, Technical Note, Case Report, Lab Report, Negative Result等）。

期刊主页：

http://www.springer.com/journal/42242

http://www.jzus.zju.edu.cn/ （国内可下载全文）

在线投稿地址：

http://www.editorialmanager.com/bdmj/default.aspx

来源：生物设计与制造BDM

声明：仅代表作者个人观点，用于研究用途，作者水平有限，如有不科学之处，请在下方留言指正！