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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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© 3D Science Valley White Paper


Txhim kho qhov ua tau zoo thaum ntxov thiab ntev -

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Cov ntaub ntawv tshawb fawb ntsig txog luam tawm hauv phau ntawv 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


Cov pob txha loj segmental defects vim raug mob, kis kab mob, los yog qog resection yeej ib txwm yog ib qho teeb meem nyuaj. Kwv yees li 5 feem pua ​​​​-10 feem pua ​​​​ntawm cov pob txha tawg muaj kev ncua kev sib koom ua ke lossis kev tsis sib haum xeeb, thiab yuav luag tag nrho cov pob txha segmental poob tshwm sim hauv nonunion. Thoob plaws ntiaj teb, ntau tshaj 2.2 lab pob txha grafts tau ua txhua xyoo los kho cov pob txha tsis xws luag hauv orthopaedics, neurosurgery, thiab kho hniav.


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.


Txawm li cas los xij, kev xyaum kho mob qhia tau tias cov kev kho mob no tsis zoo thiab qee zaum txawm tias tsis ntseeg. Kev thauj pob txha los ntawm cov txheej txheem Ilizarov feem ntau siv sijhawm ob peb lub hlis los kho, thaum lub sijhawm tus neeg mob tsis tuaj yeem txav mus tau ib txwm. Txoj kev no tseem tsawg dua yuav raug siv rau kev kho mob ntawm ntau -segmental skeletal defects ntawm tus txha nraub qaum. Cov txheej txheem Masquelet thiab cov txheej txheem ntawm autologous vascularized cortical pob txha grafting pab txhim kho pob txha fusion, tab sis nws yog ib qho nyuaj rau ua tiav tam sim tom qab kev ua haujlwm stabilization. Vim qhov xav tau ntau ntawm cov pob txha allogeneic / autologous raws li cov khoom siv pob txha, kev tshem tawm cov pob txha ntxiv (xws li cov pob txha iliac) feem ntau yuav tsum tau. Cov txheej txheem ntawm kev cog cov titanium mesh rau hauv cov pob txha tsis zoo hauv cheeb tsam muab kev yooj yim rau kev siv ntau yam khoom siv graft rau qee yam, tab sis nws cov nyhuv fixation yog txwv, thiab nws kuj muaj qhov tsis zoo ntawm kev yooj yim loosening, kev tawg lossis kev hloov pauv. Qhov tseeb, cov tswv yim xws li Ilizarov thiab Masquelet kuj nyuaj rau siv rau hauv qee qhov chaw dissociation, xws li 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.


thaiv 3D luam tawm ntxeem tau titanium cog


"Implant-bone" interface fusion


Piv nrog rau cov saum toj no-txoj kev hais txog uas yuav tsum tau ib tug loj npaum li cas ntawm allogeneic/autologous pob txha filling, daim ntawv thov ntawm 3D- luam porous titanium alloy implants los kho thiab reconstruct pob txha tsis xws luag zoo li muaj cuab kev zoo. Ua ntej, cov khoom cog tuaj yeem raug kho raws li cov duab ntawm cov pob txha tsis xws luag, tsis tas yuav muaj pob txha graft; Tsis tas li ntawd, raws li qhov zoo ntawm cov hlau prosthesis, cov cuab yeej fixation tuaj yeem tsim kom muaj kev ruaj ntseg tam sim ntawm cov pob txha thiab cov pob txha uas nyob ib sab, kom tus neeg mob tuaj yeem tawm ntawm txaj ntxov tom qab kev phais; Porous structural nta, nyiam cov pob txha uas nyob ib sab kom loj hlob mus rau hauv nws, thiab thaum kawg ua tiav mus tas li fusion ntawm cog - pob txha cuam tshuam.

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Daim duab 1. Radiological thiab biomechanical tsom xam ntawm 3D luam porous Ti6A14V implants rau reconstruct ib tug 4 cm femoral defect. (A) X-ray duab ntawm 1, 3 thiab 6 lub hlis tom qab implantation (i-iii) xam tomography duab ntawm 1, 3 thiab 6 lub hlis tom qab cog (iv-vi) . Cov xub xiav qhia cov pob txha tshiab ntawm qhov chaw tsis xws luag lossis nyob rau sab nrauv ntawm qhov cog. (vii) Radiological qhab nia ntawm txhua pab pawg. (n=4) (B) MicroCT 3D reconstruction dluab (i-iii) ntawm pawg 1, 3, thiab 6 lub hlis tom qab kev txi (grey qhia titanium alloy, ntsuab qhia cov pob txha tshiab). (iv) Cov txiaj ntsig ntau ntawm cov pob txha ntim feem hauv lub peri- cog thiab hauv - thaj tsam ntawm txhua pab pawg (n=4).


Txawm li cas los xij, kev kho mob cov txiaj ntsig ntawm kev siv 3D luam tawm porous implants los kho cov pob txha tsis xws luag (tshwj xeeb tshaj yog loj- ntu cov pob txha tsis xws luag) yuav tsum tsis yog tsuas yog kev lees paub ntawm kev soj ntsuam cov txiaj ntsig ntawm kev ua raws li- cov neeg mob, tab sis kuj yog Cov txiaj ntsig ntawm cov kev tshawb fawb txog tsiaj txhu uas muaj feem xyuam ua pov thawj. Txog qhov kawg no, pab pawg tshawb fawb tau ua tiav hauv - kev tshawb nrhiav thiab kev tshawb fawb tob tob.

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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.

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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.

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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.

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Daim duab 5. 3D- luam tawm porous Ti6Al4V implant kom rov tsim kho femoral defect (case 2). X ntawm lub reconstructed 11 cm femoral defect tam sim ntawd tom qab lub xeem phais (A) thiab 2 (B), 5 lub hlis (C), 8 lub hlis (D), 14 lub hlis (E) thiab 20 lub hlis (F) tom qab implantation kab duab. Cov xub xiav qhia osseointegration ntawm cog thiab tus tswv pob txha.

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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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