Laubach Markus, Hildebrand Frank, Suresh Sinduja, Wagels Michael, Kobbe Philipp, Gilbert Fabian, Kneser Ulrich, Holzapfel Boris M, Hutmacher Dietmar W
Australian Research Council (ARC) Training Centre for Multiscale 3D Imaging, Modelling and Manufacturing (M3D Innovation), Queensland University of Technology, Brisbane, QLD 4000, Australia.
Centre for Biomedical Technologies, School of Mechanical, Medical and Process Engineering, Queensland University of Technology, Brisbane, QLD 4059, Australia.
J Funct Biomater. 2023 Jun 27;14(7):341. doi: 10.3390/jfb14070341.
The treatment of bone defects remains a challenging clinical problem with high reintervention rates, morbidity, and resulting significant healthcare costs. Surgical techniques are constantly evolving, but outcomes can be influenced by several parameters, including the patient's age, comorbidities, systemic disorders, the anatomical location of the defect, and the surgeon's preference and experience. The most used therapeutic modalities for the regeneration of long bone defects include distraction osteogenesis (bone transport), free vascularized fibular grafts, the Masquelet technique, allograft, and (arthroplasty with) mega-prostheses. Over the past 25 years, three-dimensional (3D) printing, a breakthrough layer-by-layer manufacturing technology that produces final parts directly from 3D model data, has taken off and transformed the treatment of bone defects by enabling personalized therapies with highly porous 3D-printed implants tailored to the patient. Therefore, to reduce the morbidities and complications associated with current treatment regimens, efforts have been made in translational research toward 3D-printed scaffolds to facilitate bone regeneration. Three-dimensional printed scaffolds should not only provide osteoconductive surfaces for cell attachment and subsequent bone formation but also provide physical support and containment of bone graft material during the regeneration process, enhancing bone ingrowth, while simultaneously, orthopaedic implants supply mechanical strength with rigid, stable external and/or internal fixation. In this perspective review, we focus on elaborating on the history of bone defect treatment methods and assessing current treatment approaches as well as recent developments, including existing evidence on the advantages and disadvantages of 3D-printed scaffolds for bone defect regeneration. Furthermore, it is evident that the regulatory framework and organization and financing of evidence-based clinical trials remains very complex, and new challenges for non-biodegradable and biodegradable 3D-printed scaffolds for bone regeneration are emerging that have not yet been sufficiently addressed, such as guideline development for specific surgical indications, clinically feasible design concepts for needed multicentre international preclinical and clinical trials, the current medico-legal status, and reimbursement. These challenges underscore the need for intensive exchange and open and honest debate among leaders in the field. This goal can be addressed in a well-planned and focused stakeholder workshop on the topic of patient-specific 3D-printed scaffolds for long bone defect regeneration, as proposed in this perspective review.
骨缺损的治疗仍然是一个具有挑战性的临床问题，再次干预率高、发病率高，导致医疗成本高昂。手术技术在不断发展，但治疗结果可能受到多个参数的影响，包括患者的年龄、合并症、全身性疾病、缺损的解剖位置以及外科医生的偏好和经验。长骨缺损再生最常用的治疗方式包括牵张成骨（骨搬运）、游离带血管腓骨移植、Masquelet技术、同种异体骨移植以及（人工关节置换联合）大型假体。在过去25年中，三维（3D）打印作为一种突破性的逐层制造技术，能够直接从3D模型数据生产最终部件，已经兴起并通过使用为患者量身定制的高度多孔3D打印植入物实现个性化治疗，从而改变了骨缺损的治疗方式。因此，为了降低与当前治疗方案相关的发病率和并发症，在转化研究中已致力于3D打印支架以促进骨再生。三维打印支架不仅应提供用于细胞附着和随后骨形成的骨传导表面，还应在再生过程中为骨移植材料提供物理支撑和容纳，促进骨长入，同时，骨科植入物通过刚性、稳定的外部和/或内部固定提供机械强度。在这篇观点综述中，我们着重阐述骨缺损治疗方法的历史，评估当前的治疗方法以及最新进展，包括关于3D打印支架用于骨缺损再生的优缺点的现有证据。此外，显然基于证据的临床试验的监管框架、组织和资金仍然非常复杂，并且骨再生用非生物可降解和生物可降解3D打印支架面临的新挑战正在出现，但尚未得到充分解决，例如特定手术适应症的指南制定、所需多中心国际临床前和临床试验的临床可行设计概念、当前的医疗法律地位以及报销问题。这些挑战凸显了该领域领导者之间进行深入交流以及公开坦诚辩论的必要性。正如本观点综述中所提议的，在一个精心策划且重点突出的利益相关者研讨会上，可以围绕用于长骨缺损再生的患者特异性3D打印支架这一主题来实现这一目标。
