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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Kertas penyelidikan berkaitan yang diterbitkan dalam jurnal 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
Kecacatan tulang segmen besar akibat trauma, jangkitan, atau reseksi tumor sentiasa menjadi masalah klinikal yang mencabar. Kira-kira 5 peratus -10 peratus patah tulang mengalami kesatuan tertunda atau nonunion, dan hampir semua kehilangan tulang segmen mengakibatkan nonunion. Di seluruh dunia, lebih daripada 2.2 juta cantuman tulang dilakukan setiap tahun untuk merawat kecacatan tulang dalam ortopedik, pembedahan saraf dan pergigian.
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.
Walau bagaimanapun, amalan klinikal menunjukkan bahawa rawatan ini tidak sesuai dan kadangkala tidak boleh dipercayai. Pengangkutan tulang melalui prosedur Ilizarov biasanya mengambil masa beberapa bulan untuk sembuh, pada masa itu pesakit tidak dapat bergerak secara normal. Kaedah ini lebih kecil kemungkinannya digunakan untuk rawatan kecacatan rangka berbilang{0}}segmental tulang belakang. Teknik Masquelet dan kaedah cantuman tulang kortikal vascularized autologous membantu meningkatkan gabungan tulang, tetapi sukar untuk mencapai penstabilan segera selepas pembedahan. Disebabkan keperluan untuk sejumlah besar tulang alogenik/autologus sebagai bahan cantuman tulang, pembuangan tulang pembedahan tambahan (seperti pembuangan tulang iliac) selalunya diperlukan. Kaedah menanam mesh titanium ke dalam kawasan kecacatan tulang memberikan kemudahan untuk penggunaan pelbagai bahan cantuman pada tahap tertentu, tetapi kesan penetapannya adalah terhad, dan ia juga mempunyai kekurangan mudah melonggarkan, penurunan atau anjakan. Malah, teknik seperti Ilizarov dan Masquelet juga sukar digunakan di tapak pemisahan tertentu, seperti metafisis.
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.
blok cetakan 3D implan titanium berliang
"Implant-bone" interface fusion
Berbanding dengan kaedah-yang dinyatakan di atas yang memerlukan sejumlah besar pengisian tulang alogenik/autolog, penggunaan implan aloi titanium berliang 3D{2}}dicetak untuk membaiki dan membina semula kecacatan tulang nampaknya mempunyai kelebihan yang jelas. Pertama, implan boleh disesuaikan dengan tepat mengikut bentuk kecacatan tulang, tanpa memerlukan cantuman tulang; di samping itu, mengikut kelebihan prostesis logam, peranti penetapan boleh direka bentuk untuk mencapai penstabilan segera antara implan dan tulang bersebelahan, supaya pesakit boleh bangun awal selepas pembedahan; Ciri struktur berliang, menarik tisu tulang bersebelahan untuk tumbuh ke dalamnya, dan akhirnya mencapai gabungan kekal antara muka tulang-implan.

Rajah 1. Analisis radiologi dan biomekanik implan Ti6A14V berliang cetakan 3D untuk membina semula kecacatan femoral 4 cm. (A) Imej X-ray pada 1, 3 dan 6 bulan selepas implantasi (i-iii) Imej tomografi yang dikira pada 1, 3 dan 6 bulan selepas implantasi (iv-vi) . Anak panah biru menunjukkan tulang yang baru terbentuk di tapak kecacatan atau pada permukaan luar implan. (vii) Skor radiologi setiap kumpulan. (n=4) (B) Imej pembinaan semula 3D MicroCT (i-iii) kumpulan 1, 3 dan 6 bulan selepas pengorbanan (kelabu menunjukkan aloi titanium, hijau menunjukkan tulang baharu). (iv) Keputusan kuantitatif pecahan isipadu tulang dalam peri-implan dan dalam-kawasan foram setiap kumpulan (n=4).
Walau bagaimanapun, kesan terapeutik klinikal menggunakan implan berliang bercetak 3D untuk membaiki kecacatan tulang (terutamanya-kecacatan tulang segmen besar) memerlukan bukan sahaja pengesahan hasil pemerhatian kes-susulan, tetapi juga hasil kajian eksperimen haiwan yang berkaitan sebagai bukti. Untuk tujuan ini, pasukan penyelidik menjalankan-penerokaan dan penyelidikan yang mendalam dan sistematik.

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,>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.


Rajah 5. 3D-mencetak implan Ti6Al4V berliang untuk membina semula kecacatan femoral (kes 2). X daripada kecacatan femoral 11 cm yang dibina semula sejurus selepas pembedahan terakhir (A) dan 2 (B), 5 bulan (C), 8 bulan (D), 14 bulan (E) dan 20 bulan (F) selepas imej garis implantasi. Anak panah biru menunjukkan osseointegrasi antara implan dan tulang perumah.

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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