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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Bioactive Materials 저널에 게재된 관련 연구 논문
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
외상, 감염 또는 종양 절제로 인한 큰 분절 골 결손은 항상 어려운 임상 문제였습니다. 골절의 약 5%-10%는 지연된 유합 또는 불유합을 경험하고 거의 모든 분절성 골 소실은 불유합을 초래합니다. 전 세계적으로 매년 220만 개 이상의 뼈 이식이 정형외과, 신경외과 및 치과에서 뼈 결함을 치료하기 위해 시행됩니다.
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.
그러나 임상 실습에 따르면 이러한 치료법은 이상적이지 않으며 때로는 신뢰할 수 없는 경우도 있습니다. Ilizarov 절차를 통한 뼈 이동은 일반적으로 치유되는 데 몇 달이 걸리며 이 기간 동안 환자는 정상적으로 움직일 수 없습니다. 이 방법은 척추의 다분절 골격 결함 치료에{0}사용할 가능성이 훨씬 적습니다. Masquelet 기법과 자가혈관피질골이식법은 골유합력을 높이는 데 도움이 되지만 수술 후 즉각적인 안정화가 어렵다. 골 이식재로 많은 양의 동종/자가골이 필요하기 때문에 추가적인 외과적 골 제거(예: 장골 제거)가 필요한 경우가 많습니다. 골결손 부위에 티타늄 메쉬를 이식하는 방법은 다양한 이식재의 적용에 어느 정도 편의성을 제공하지만 고정 효과가 제한적이며 쉽게 풀림, 침하 또는 변위가 발생하는 단점이 있습니다. 사실 Ilizarov, Masquelet 등의 기법도 형이상과 같은 특정 해리 부위에 적용하기 어렵다.
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.
블록 3D 프린트 다공성 티타늄 임플란트
"Implant-bone" interface fusion
많은 양의 동종/자가 뼈 충전이 필요한 위에서 언급한{0}}방법과 비교할 때 3D 인쇄된 다공성 티타늄 합금 임플란트를{2} 뼈 결함을 복구하고 재건하는 데 적용하는 것은 분명한 이점이 있는 것 같습니다. 첫째, 골이식을 할 필요 없이 골 결손의 형태에 따라 임플란트를 정밀하게 맞춤화할 수 있습니다. 또한, 금속 보철물의 장점에 따라 고정 장치를 설계하여 임플란트와 인접 뼈 사이를 즉시 안정화하여 환자가 수술 후 일찍 침대에서 나올 수 있습니다. 다공성 구조적 특징, 인접한 뼈 조직을 끌어당겨 그 안으로 성장하고 마침내 임플란트 뼈 인터페이스의 영구적인 융합을 달성합니다.{3}}

그림 1. 4cm 대퇴부 결함을 재건하기 위해 3D 인쇄된 다공성 Ti6A14V 임플란트의 방사선 및 생체 역학 분석. (A) 이식 후 1, 3, 6개월의 X-X선 이미지 (i-iii) 이식 후 1, 3, 6개월의 컴퓨터 단층촬영 이미지(iv{13}}vi) . 파란색 화살표는 결함 부위 또는 임플란트 외부 표면에 새로 형성된 뼈를 나타냅니다. (vii) 각 그룹의 방사선학적 점수. (n{14}}) (B) 희생 후 그룹 1, 3, 6개월의 MicroCT 3D 재구성 이미지(i{16}}iii)(회색은 티타늄 합금, 녹색은 새로운 뼈를 나타냄). (iv) 임플란트 주변 및 각 그룹(n{22}})의 구멍 영역에서 골 부피 분율의 정량적 결과.
그러나 3D 인쇄된 다공성 임플란트를 사용하여 뼈 결함(특히 큰{1}}골절 결함)을 치료하는 임상 치료 효과는 후속 사례의 관찰 결과 확인뿐만 아니라{2}} 증거로 관련 동물 실험 연구의 결과. 이를 위해 연구팀은-심도 있고 체계적인 탐색과 연구를 수행했습니다.

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.


그림 5. 대퇴골 결함을 재건하기 위해 3D-인쇄된 다공성 Ti6Al4V 임플란트(사례 2). 마지막 수술 직후의 재건된 11cm 대퇴부 결손부(A)와 2(B), 5개월(C), 8개월(D), 14개월(E), 20개월(F)의 임플란트 라인 이미지. 파란색 화살표는 임플란트와 호스트 뼈 사이의 골유착을 나타냅니다.

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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