Joint degeneration and large or complex bone defects are a significant source of morbidity and diminished quality of life worldwide. There is an unmet need for a functional implant with near-native biomechanical properties. The potential for their generation using 3D bioprinting (3DBP)-based tissue engineering methods was assessed. We systematically reviewed the current state of 3DBP in orthoregeneration. This review was performed using PubMed and Web of Science. Primary research articles reporting 3DBP of cartilage, bone, vasculature, and their osteochondral and vascular bone composites were considered. Full text English articles were analyzed. Over 1300 studies were retrieved, after removing duplicates, 1046 studies remained. After inclusion and exclusion criteria were applied, 114 articles were analyzed fully. Bioink material types and combinations were tallied. Cell types and testing methods were also analyzed. Nearly all papers determined the effect of 3DBP on cell survival. Bioink material physical characterization using gelation and rheology, and construct biomechanics were performed. In vitro testing methods assessed biochemistry, markers of extracellular matrix production and/or cell differentiation into respective lineages. In vivo proof-of-concept studies included full-thickness bone and joint defects as well as subcutaneous implantation in rodents followed by histological and µCT analyses to demonstrate implant growth and integration into surrounding native tissues. Despite its relative infancy, 3DBP is making an impact in joint and bone engineering. Several groups have demonstrated preclinical efficacy of mechanically robust constructs which integrate into articular joint defects in small animals. However, notable obstacles remain. Notably, researchers encountered pitfalls in scaling up constructs and establishing implant function and viability in long term animal models. Further, to translate from the laboratory to the clinic, standardized quality control metrics such as construct stiffness and graft integration metrics should be established with investigator consensus. While there is much work to be done, 3DBP implants have great potential to treat degenerative joint diseases and provide benefit to patients globally.

中文翻译：

---

生物 3D 打印技术在正射再生中的应用系统评价：当前成就和开放挑战

关节退化和大的或复杂的骨缺损是全世界发病率和生活质量下降的重要来源。对具有接近天然生物力学特性的功能性植入物的需求尚未得到满足。评估了使用基于 3D 生物打印 (3DBP) 的组织工程方法生成它们的潜力。我们系统地回顾了 3DBP 在正射再生中的现状。该审查是使用 PubMed 和 Web of Science 进行的。考虑了报告软骨、骨、脉管系统及其骨软骨和血管骨复合材料的 3DBP 的主要研究文章。对全文英文文章进行了分析。检索到超过 1300 项研究，删除重复项后，剩下 1046 项研究。应用纳入和排除标准后，对 114 篇文章进行了全面分析。对生物墨水材料类型和组合进行了统计。还分析了细胞类型和测试方法。几乎所有的论文都确定了 3DBP 对细胞存活的影响。使用凝胶化和流变学对生物墨水材料进行物理表征，并进行构建生物力学。体外测试方法评估了生物化学、细胞外基质产生和/或细胞分化成各自谱系的标志物。体内概念验证研究包括啮齿动物的全层骨和关节缺损以及皮下植入，然后进行组织学和 µCT 分析，以证明植入物的生长和与周围天然组织的整合。尽管它还处于起步阶段，但 3DBP 正在对关节和骨骼工程产生影响。几个小组已经证明了机械坚固结构的临床前功效，这些结构整合到小动物的关节缺损中。然而，值得注意的障碍仍然存在。值得注意的是，研究人员在扩大构建体和在长期动物模型中建立植入物功能和生存能力时遇到了陷阱。此外，为了从实验室转化为临床，应建立标准化的质量控制指标，例如结构刚度和移植物整合指标，并与研究者达成共识。虽然还有很多工作要做，但 3DBP 植入物在治疗退行性关节疾病和为全球患者带来益处方面具有巨大潜力。研究人员在放大构建体和在长期动物模型中建立植入物功能和生存能力时遇到了陷阱。此外，为了从实验室转化为临床，应建立标准化的质量控制指标，例如结构刚度和移植物整合指标，并与研究者达成共识。虽然还有很多工作要做，但 3DBP 植入物在治疗退行性关节疾病和为全球患者带来益处方面具有巨大潜力。研究人员在放大构建体和在长期动物模型中建立植入物功能和生存能力时遇到了陷阱。此外，为了从实验室转化为临床，应建立标准化的质量控制指标，例如结构刚度和移植物整合指标，并与研究者达成共识。虽然还有很多工作要做，但 3DBP 植入物在治疗退行性关节疾病和为全球患者带来益处方面具有巨大潜力。