“Innovation and translation of biological and biomaterial treatment for challenging musculoskeletal disorders”

Background The periosteum stem cells (PSCs) plays a critical role in bone regeneration and defect reconstruction. Insertion of polymethyl methacrylate (PMMA) bone cement can form an induced membrane(IM) and showed promising strategy for bone defect reconstruction, the underlying mechanism remains unclear. Our study sought to determine whether IM-derived cells(IMDCs) versus PSCs have similar characteristics in bone regeneration. Methods IM and periosteum were harvested from ten bone defect patients treated with PMMA, the IMDCs and PSCs were isolated respectively. Morphological, functional and molecular evaluation was performed and matched for comparison. Results Both progenitor-like IMDCs and PSCs were successfully isolated. In vitro, we found IMDCs were similar to PSCs in morphology, colony forming capacity and expression of surface marker(CD90+, CD73+, CD105+, CD34-/CD45-). Meanwhile, these IMSCs displayed multipotency with chondrogenic, adipogenic and osteogenic differentiation, but differed in some IMSCs(3/10) population showing relatively poor osteogenic differentiation. The molecular profiles suggests that cell cycle and DNA replication signaling pathways were associated with these varying osteogenic potential. In vivo, we established a cell-based tissue-engineered bone by seeding IMDSs/PSCs to demineralized bone matrix (DBM) scaffold and demonstrated both IMDSs and PSCs enhanced bone regeneration in SCID mice bone defect model compared with DBM alone. Conclusion Our data demonstrated IM containing multipotent progenitor cells similar to that periosteum promoting bone regeneration, and indicated the existence of multiple subsets in osteogenic differentiation. Overall, the study provided a cellular and molecular insights in understanding the successful or failed outcome of bone defect healing. The translational potential of this article: This study confirmed IMDCs and PSCs share similar regeneration capacity and inform a translation potential of that cellular therapy applying IMDCs in bone defect repair.

Background Currently, metal implants are widely used in orthopedic surgeries, including fracture fixation, spinal fusion, joint replacement, and bone tumor defect repair. However, conventional implants are difficult to be customized according to the recipient's skeletal anatomy and defect characteristics, leading to difficulties in meeting the individual needs of patients. Additive manufacturing (AM) or three-dimensional (3D) printing technology, an advanced digital fabrication technique capable of producing components with complex and precise structures, offers opportunities for personalization. Methods We systematically reviewed the literature on 3D printing orthopedic metal implants over the past 10 years. Relevant animal, cellular, and clinical studies were searched in PubMed and Web of Science. In this paper, we introduce the 3D printing method and the characteristics of biometals and summarize the properties of 3D printing metal implants and their clinical applications in orthopedic surgery. On this basis, we discuss potential possibilities for further generalization and improvement. Results 3D printing technology has facilitated the use of metal implants in different orthopedic procedures. By combining medical images from techniques such as CT and MRI, 3D printing technology allows the precise fabrication of complex metal implants based on the anatomy of the injured tissue. Such patient-specific implants not only reduce excessive mechanical strength and eliminate stress-shielding effects, but also improve biocompatibility and functionality, increase cell and nutrient permeability, and promote angiogenesis and bone growth. In addition, 3D printing technology has the advantages of low cost, fast manufacturing cycles, and high reproducibility, which can shorten patients' surgery and hospitalization time. Many clinical trials have been conducted using customized implants. However, the use of modeling software, the operation of printing equipment, the high demand for metal implant materials, and the lack of guidance from relevant laws and regulations have limited its further application. Conclusions There are advantages of 3D printing metal implants in orthopedic applications such as personalization, promotion of osseointegration, short production cycle, and high material utilization. With the continuous learning of modeling software by surgeons, the improvement of 3D printing technology, the development of metal materials that better meet clinical needs, and the improvement of laws and regulations, 3D printing metal implants can be applied to more orthopedic surgeries. The translational potential of this paper Precision, intelligence, and personalization are the future direction of orthopedics. It is reasonable to believe that 3D printing technology will be more deeply integrated with artificial intelligence, 4D printing, and big data to play a greater role in orthopedic metal implants and eventually become an important part of the digital economy. We aim to summarize the latest developments in 3D printing metal implants for engineers and surgeons to design implants that more closely mimic the morphology and function of native bone.

Background Tibial Cortex Transverse Transport (TTT) has been demonstrated to be an effective treatment for unilateral diabetic foot ulcers (UDFUs). However, this retrospective study was designed to compare the efficacy and safety of unilateral TTT on bilateral diabetic foot ulcers (BDFUs). Methods This retrospective study included a review of patients with TTT treated from January 2017 to August 2019, Propensity Score Matching (PSM) was performed to compare patients with BDFUs to those with UDFUs. Ulcer healing, recurrence, and major amputation rates were evaluated at 1-year follow-up. Changes in foot vessels were assessed in the BDFUs group using computed tomography angiography (CTA). Results A total of 140 patients with DFUs (106 UDFUs and 34 BDFUs) were included in the study. UDFUs and BDFUs were matched in a 1:1 ratio (34 in each group) using PSM. No significant difference was observed at 1-year-follow-up [91.2% (31/34) vs. 76.5% (26/34), OR 0.315 (95% CI 0.08 to 1.31), P ​= ​0.10] and 6-month-follow-up [70.6% (24/34) vs. 50.0% (17/34), OR 0.85 (95% CI 0.15 to 1.13), P ​= ​0.08] in two groups. Significant differences in rates of major amputation and recurrence between the groups (P ​> ​0.05) were not observed. The BDFUs group appeared more angiogenesis of the foot by CTA after 8 weeks of operation. Conclusion Results of this study suggest that severe BDFUs can be effectively treated by unilateral TTT. TTT is easy to operate and effective, which may be a good alternative for treating severe BDFUs. The translational potential of this article In previous retrospective clinical studies, TTT has demonstrated promising clinical outcomes in the management of diabetic foot ulcers. In this current study, we aim to investigate the potential use of TTT in treating distant tissue defects by evaluating the limited availability and safety of TTT for the management of bilateral diabetic foot. While additional basic and clinical research is necessary to fully elucidate the underlying mechanisms, our study offers insight into the potential therapeutic use of TTT for this condition.