The current concept of large-segment bone defect treatment is still to complete the replacement and fusion of bone tissue by means of autologous, allogeneic or artificial bone graft filling, that is, "bone-bone" interface fusion. The theory is deeply rooted, but the clinical effect is poor. A research team from research institutions such as Peking University Third Hospital used a custom-made 3D-printed titanium alloy porous implant to repair large-segment bone defects in a research work, realizing the patient's early limb function recovery and long-term "implant- Reliable fusion of the "bone" interface, with significantly improved efficacy.
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Improve early and long-term efficacy
Related research papers published in the journal Bioactive Materials
https://doi.org/10.1016/j.bioactmat.2021.03.030
This research work was supported by the National Key RD Program of the Ministry of Science and Technology of the People's Republic of China (2016YFB1101501).
block Traditional "bone-bone" fusion treatment concept
Large segmental bone defects due to trauma, infection, or tumor resection have always been a challenging clinical problem. About 5 percent -10 percent of fractures experience delayed union or nonunion, and nearly all segmental bone loss results in nonunion. Worldwide, more than 2.2 million bone grafts are performed annually to treat bone defects in orthopaedics, neurosurgery, and dentistry.
Classical techniques for the treatment of large bone defects include the Ilizarov technique, the induction of bone regeneration through biofilms (Masquelet technique), autologous vascularized cortical bone grafting, and titanium mesh (filled with autologous or allogeneic bone) implantation techniques. The above treatments have their own characteristics depending on the technology, but they are essentially based on the concept of "bone-bone" fusion, that is, autologous bone, allogeneic bone or artificial bone is transplanted and filled in the defect area, and replaced by bone tissue repair. Complete the connection and fusion of the bones at both ends of the defect area.
However, clinical practice shows that these treatments are not ideal and sometimes even unreliable. Bone transport through the Ilizarov procedure typically takes several months to heal, during which time the patient is unable to move normally. This method is even less likely to be used for the treatment of multi-segmental skeletal defects of the spine. The Masquelet technique and the method of autologous vascularized cortical bone grafting help to enhance bone fusion, but it is difficult to achieve immediate postoperative stabilization. Due to the need for a large amount of allogeneic/autologous bone as bone graft material, additional surgical bone removal (such as iliac bone removal) is often required. The method of implanting the titanium mesh into the bone defect area provides convenience for the application of various graft materials to a certain extent, but its fixation effect is limited, and it also has the shortcomings of easy loosening, subsidence or displacement. In fact, techniques such as Ilizarov and Masquelet are also difficult to apply in certain dissociation sites, such as the metaphysis.
To sum up, various traditional techniques based on the concept and theory of "bone-bone" fusion have many shortcomings or defects in the treatment of large segmental bone defects: the treatment process is long, and the limbs of patients after surgery are not immediately, early, or surgically removed. After a long period of time can not bear weight.
block 3D prints porous titanium implants
"Implant-bone" interface fusion
Compared with the above-mentioned methods that require a large amount of allogeneic/autologous bone filling, the application of 3D-printed porous titanium alloy implants to repair and reconstruct bone defects seems to have obvious advantages. First, the implants can be precisely customized according to the shape of the bone defect, without the need for Bone graft; in addition, according to the advantages of metal prosthesis, a fixation device can be designed to achieve immediate stabilization between the implant and adjacent bones, so that the patient can get out of bed early after surgery; Porous structural features, attracting adjacent bone tissue to grow into it, and finally achieve permanent fusion of the implant-bone interface.
Figure 1. Radiological and biomechanical analysis of 3D printed porous Ti6A14V implants to reconstruct a 4 cm femoral defect. (A) X-ray images at 1, 3 and 6 months after implantation (i-iii) Computed tomography images at 1, 3 and 6 months after implantation (iv-vi). Blue arrows indicate newly formed bone at the defect site or on the outer surface of the implant. (vii) Radiological score of each group. (n=4) (B) MicroCT 3D reconstruction images (i-iii) of groups 1, 3, and 6 months after sacrifice (grey indicates titanium alloy, green indicates new bone). (iv) Quantitative results of bone volume fraction in the peri-implant and in-foram regions of each group (n=4).
However, the clinical therapeutic effect of using 3D printed porous implants to repair bone defects (especially large-segment bone defects) requires not only the confirmation of the observation results of follow-up cases, but also the results of relevant animal experimental studies as evidence. To this end, the research team carried out in-depth and systematic exploration and research.
Figure 2. Biomechanical analysis of 3D printed porous Ti6A14V implants for reconstruction of 4 cm femoral defects. (A) Three-point flexural strength of each group of samples (n = 4) (B) Stress distribution of the "implant-bone" complex at (ii) 1000 N, (iv) 2000 N and (vi) 3000 N. Displacement distribution of the "implant-bone" complex at (i) 1000N, (iii) 2000N and (v) 3000N. (p<0.01,><>
In view of the shortcomings of the traditional "bone-bone" fusion method in the treatment of large-segment bone defects, and based on the experience of exploratory treatment of large-segment bone defects and the results of relevant animal experiments, the research team proposed a new large-segment bone defect. The technology and concept of bone defect repair and reconstruction: "implant-bone" interface fusion.
Figure 3. Histological analysis of 3D-printed porous Ti6A14V implants for reconstruction and repair of 4 cm long femoral defects. (A) Goldner's trichrome staining (i-iii) of 1, 3 and 6 month groups. (iv) Quantitative results of implant-bone growth and implant-bone contact rates in the three groups. (v) The ratio of mineralized bone to osteoid in each group (n = 10). (B) Fluorescent labeling of new bone around the implant and in the pores. (White arrows indicate titanium columns, green and yellow bands indicate calcein- and tetracycline-labeled new bone, respectively). (i) Osseointegration around the implant in the 1-, (iii) 3- and (v) 6-month groups. (ii) 1-, (iv) 3-, (vi) osseointegration in plant pores in 6-month groups.
The basic idea is: a. The 3D printed porous titanium alloy prosthesis is implanted into the bone defect area, and the two ends of the implanted prosthesis are connected and fixed with the adjacent host bone, so as to realize the immediate (or early) functional recovery of the patient's limb; b . The implanted prosthesis is designed as a porous structure to attract adjacent bone tissue to grow into it and surround it to achieve "implant-bone" interface fusion.
Figure 4. 3D printing of porous Ti6Al4V implants to reconstruct spinal bone defects (case 1). (A) (i-vi) 1 month (i), 3 months (ii), 7 (months iii), 12 months (iv), 24 months (v) and 32 (vi) postoperatively "Implant-bone" X-ray image of Moon. Blue arrows indicate the implant-bone interface or new bone on the outer surface of the implant. (B) CT images at 3 months (i), 7 months (ii), 12 months (iii), 28 months (iv), 32 months (v) and 36 months (vi) after surgery. Blue arrows indicate the implant-bone interface or newly formed bone on the outside of the implant.
Of course, if the porous structure of the implant grows through the bone tissue, it is ideal to form a "bone-bone" fusion, but it is difficult to become a reality. However, when the two ends of the implant prosthesis are effectively fused with the host bone at a distance of several millimeters, it can already meet the needs of the patient to restore the motor function of the limb. The research team applied the 3D-printed porous titanium alloy implants made by electron beam melting (EBM) technology to the clinical treatment of a group of large-segment bone defects, and achieved better than expected results. At the same time, the research team used the small-tailed Han sheep to create a long-segment femoral defect model to study the osseointegration characteristics of this method, and to provide a supporting basis for the treatment effect of clinical cases.
Figure 5. 3D-printed porous Ti6Al4V implant to reconstruct femoral defect (case 2). X of the reconstructed 11 cm femoral defect immediately after the last surgery (A) and 2 (B), 5 months (C), 8 months (D), 14 months (E) and 20 months (F) after implantation line image. Blue arrows indicate osseointegration between implant and host bone.
Figure 6. 3D-printed porous Ti6Al4V implant to reconstruct pelvic bone defect (case 3). Photographs of the actual "implant-bone" complex specimen taken from (A) lateral and (B) anteroposterior views. The location of the "implant-bone" interface area indicated by the blue arrow (C) Histological image of the "implant-bone" interface, showing new bone growing into the porous implant pores. Micro-CT images of the "implant-bone" contact area in (D) midsagittal plane, (E) coronal plane and (F) transverse plane.
In this study, the research team successfully treated large segmental bone defects caused by various etiologies by 3D printing porous titanium alloy implants without using autologous/allogeneic bone grafts or any osteoinductive agents. immediate and long-term biomechanical stability. Animal experiments have shown that bone can grow into the pores to a certain extent and gradually remodel, so that the "implant-bone" complex can achieve long-term mechanical stability. In addition, this study also proposes a new "implant-bone" interface fusion concept for the treatment of large segmental bone defects, which is different from the traditional "bone-bone" fusion concept.
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