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.

Bone defects after trauma, infection, or tumour resection present a challenge for patients and clinicians. To date, autologous bone graft (ABG) is the gold standard for bone regeneration. To address the limitations of ABG such as limited harvest volume as well as overly fast remodelling and resorption, a new treatment strategy of scaffold-guided bone regeneration (SGBR) was developed. In a well-characterized sheep model of large to extra-large tibial segmental defects, three-dimensional (3D) printed composite scaffolds have shown clinically relevant biocompatibility and osteoconductive capacity in SGBR strategies. Here, we report four challenging clinical cases with large complex posttraumatic long bone defects using patient-specific SGBR as a successful treatment. After giving informed consent computed tomography (CT) images were used to design patient-specific biodegradable medical-grade polycaprolactone-tricalcium phosphate (mPCL-TCP, 80:20 ​wt%) scaffolds. The CT scans were segmented using Materialise Mimics to produce a defect model and the scaffold parts were designed with Autodesk Meshmixer. Scaffold prototypes were 3D-printed to validate robust clinical handling and bone defect fit. The final scaffold design was additively manufactured under Food and Drug Administration (FDA) guidelines for patient-specific and custom-made implants by Osteopore International Pte Ltd. Four patients (age: 23–42 years) with posttraumatic lower extremity large long bone defects (case 1: 4 ​cm distal femur, case 2: 10 ​cm tibia shaft, case 3: complex malunion femur, case 4: irregularly shaped defect distal tibia) are presented. After giving informed consent, the patients were treated surgically by implanting a custom-made mPCL-TCP scaffold loaded with ABG (case 2: additional application of recombinant human bone morphogenetic protein-2) harvested with the Reamer-Irrigator-Aspirator system (RIA, Synthes®). In all cases, the scaffolds matched the actual anatomical defect well and no perioperative adverse events were observed. Cases 1, 3 and 4 showed evidence of bony ingrowth into the large honeycomb pores (pores >2 ​mm) and fully interconnected scaffold architecture with indicative osseous bridges at the bony ends on the last radiographic follow-up (8–9 months after implantation). Comprehensive bone regeneration and full weight bearing were achieved in case 2 ​at follow-up 23 months after implantation. This study shows the bench to bedside translation of guided bone regeneration principles into scaffold-based bone tissue engineering. The scaffold design in SGBR should have a tissue-specific morphological signature which stimulates and directs the stages from the initial host response towards the full regeneration. Thereby, the scaffolds provide a physical niche with morphology and biomaterial properties that allow cell migration, proliferation, and formation of vascularized tissue in the first one to two months, followed by functional bone formation and the capacity for physiological bone remodelling. Great design flexibility of composite scaffolds to support the one to three-year bone regeneration was observed in four patients with complex long bone defects. This study reports on the clinical efficacy of SGBR in the treatment of long bone defects. Moreover, it presents a comprehensive narrative of the rationale of this technology, highlighting its potential for bone regeneration treatment regimens in patients with any type of large and complex osseous defects.

Key aspects of an ideal lumbar interbody cage design include stability, porosity, pore size, and surface topography, all achieved through specific material choices and geometry to mimic native bone and enhance biological integration.

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Purpose: Dissatisfaction and an impaired quality of life after total knee arthroplasty (TKA) is often associated with postsurgical anterior knee pain (AKP). The underlying pathological mechanisms are not yet fully understood. Therefore, a multifactorial approach encompassing clinical and radiological parameters seemed reasonable and promising to investigate postsurgical AKP. Methods: In this cross-sectional study, 25 patients without and 25 patients with postsurgical AKP after unilateral TKA were randomly recruited from a larger cohort of patients. Multiple clinical and radiological parameters—including real-time shear wave elastography (SWE) to measure the patellar and quadriceps tendon elasticity—were acquired and subsequently associated with AKP. For statistical analysis, SPSS (IBM, version 25) was used. Results: In total 50 participants (58.0% men, mean age 63.42 years, mean body mass index 29.75 kg/m²), having different prosthetic designs implanted, were included. Independently of key covariates, the strength of the quadriceps muscle ( p = 0.021), a thinner inlay ( p = 0.041), and a lower position of the patella ( p = 0.041) were associated with AKP. Although no correlation with AKP was found ( p = 0.346, resp. p = 0.154), we observed significantly decreased Young’s modulus of the patellar and quadriceps tendons for the involved knee compared to the uninvolved knee ( p < 0.001). Conclusion: In conclusion, quadriceps muscle strength, inlay thickness, and the patella position might be of particular relevance in avoiding postsurgical AKP. Future studies with larger sample sizes are needed to clarify the impact of quadriceps muscle strength and the postoperative patella position as well as the role of SWE as a personalized modifiable prediction marker.