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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: With increasing requirements for medical effects, and huge differences among individuals, traditional surgical instruments are difficult to meet the patients' growing medical demands. 3D printing is increasingly mature, which connects to medical services critically as well. The patient specific surgical guide plate provides the condition for precision medicine in orthopaedics. Methods: In this paper, a systematic review of the orthopedic guide template is presented, where the history of 3D-printing-guided technology, the process of guides, and basic clinical applications of orthopedic guide templates are described. Finally, the limitations of the template and possible future directions are discussed. Results: The technology of 3D printing surgical templates is increasingly mature, standard, and intelligent. With the help of guide templates, the surgeon can easily determine the direction and depth of the screw path, and choose the angle and range of osteotomy, increasing the precision, safety, and reliability of the procedure in various types of surgeries. It simplifies the difficult surgical steps and accelerates the growth of young and mid-career physicians. But some problems such as cost, materials, and equipment limit its development. Conclusions: In different fields of orthopedics, the use of guide templates can significantly improve surgical accuracy, shorten the surgical time, and reduce intraoperative bleeding and radiation. With the development of 3D printing, the guide template will be standardized and simplified from design to production and use. 3D printing guides will be further sublimated in the application of orthopedics and better serve the patients. The translational potential of this paper: Precision, intelligence, and individuation are the future development direction of orthopedics. It is more and more popular as the price of printers falls and materials are developed. In addition, the technology of meta-universe, digital twin, and artificial intelligence have made revolutionary effects on template guides. We aim to summarize recent developments and applications of 3D printing guide templates for engineers and surgeons to develop more accurate and efficient templates.

Background: Periosteum plays a significant role in bone formation and regeneration by storing progenitor cells, and also acts as a source of local growth factors and a scaffold for recruiting cells and other growth factors. Recently, tissue-engineered periosteum has been studied extensively and shown to be important for osteogenesis and chondrogenesis. Using biomimetic methods for artificial periosteum synthesis, membranous tissues with similar function and structure to native periosteum are produced that significantly improve the efficacy of bone grafting and scaffold engineering, and can serve as direct replacements for native periosteum. Many problems involving bone defects can be solved by preparation of idealized periosteum from materials with different properties using various techniques. Methods: This review summarizes the significance of periosteum for osteogenesis and chondrogenesis from the aspects of periosteum tissue structure, osteogenesis performance, clinical application, and development of periosteum tissue engineering. The advantages and disadvantages of different tissue engineering methods are also summarized. Results: The fast-developing field of periosteum tissue engineering is aimed toward synthesis of bionic periosteum that can ensure or accelerate the repair of bone defects. Artificial periosteum materials can be similar to natural periosteum in both structure and function, and have good therapeutic potential. Induction of periosteum tissue regeneration and bone regeneration by biomimetic periosteum is the ideal process for bone repair. Conclusions: Periosteum is essential for bone formation and regeneration, and it is indispensable in bone repair. Achieving personalized structure and composition in the construction of tissue engineering periosteum is in accordance with the design concept of both universality and emphasis on individual differences and ensures the combination of commonness and individuality, which are expected to meet the clinical needs of bone repair more effectively. The translational potential of this article: To better understand the role of periosteum in bone repair, clarify the present research situation of periosteum and tissue engineering periosteum, and determine the development and optimization direction of tissue engineering periosteum in the future. It is hoped that periosteum tissue engineering will play a greater role in meeting the clinical needs of bone repair in the future, and makes it possible to achieve optimization of bone tissue therapy.

Background: Xenograft bone scaffolds have advantages such as mechanical strength, sufficient source and safety. Combined with siRNA properly targeting CKIP-1, a negative regulator of osteogenesis, may contribute to the repair result of calcine bone alone. Methods: Herein, we constructed a novel xenograft bovine bone scaffold namely (DSS)6-liposome/CKIP-1 siRNA/calcine bone, the characteristics of which were investigated by confirming the effect of (DSS)6-liposome, observing the appearance and testing mechanical strength of calcine bone, and observing the combined result of CKIP-1 siRNA by FAM immunofluorescence. In addition, cytotoxicity by CCK-8 and LDH activity of L929 ​cells and MC3T3-E1 osteoblasts cultured with the scaffold were tested in vitro, primary osteoblasts proliferation, the mRNA expressions of CKIP-1, ALP, COL1-α and OCN, the protein expressions of CKIP-1, BMP-2, COL-1 and Runx2 and calcium nodules were also determined by CCK-8, RT-qPCR, western-blot and Alizarin Red staining in vitro. Then, we successively established the skull defect model for evaluating the repair result of the novel scaffold by HE staining of 2, 4, 8 and 12 weeks, immumohistochemical stainings of 2, 4, 8 and 12 weeks such as ALP, COL-1α and OCN, Mirco-CT scanning of 4 and 12 weeks and the relative parameters and so on in vivo. Results: It indicated that (DSS)6-liposome/CKIP-1 siRNA/calcine bone could successfully knock down the CKIP-1 mRNA and protein expressions, promote osteoblasts proliferation with the little cytotoxicity in vitro, increase the protein expressions of BMP-2, COL-1 and Runx2 in vitro, increase mRNA expressions of ALP, COL-1α and OCN in vitro and in vivo, and have a better bone defect repair effect with few side effects in rats after 12 weeks. Conclusion: Our research indicates (DSS)6-liposome/CKIP-1 siRNA/calcine bone could repair skull defects well in rats, and it may lay the foundation of applicating the novel xenograft bone scaffold in the clinical. The Translational potential of this article: These findings provide evidence that (DSS)6- liposome/CKIP-1 siRNA/calcine bone could be used as a novel xenograft bone scaffold for osteogenesis with the good safety.