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Mar 27, 2022

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


Gwella effeithiolrwydd-tymor cynnar a hirdymor

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Papurau ymchwil cysylltiedig a gyhoeddwyd yn y cyfnodolyn 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


Mae diffygion asgwrn segmentol mawr oherwydd trawma, haint, neu echdoriad tiwmor bob amser wedi bod yn broblem glinigol heriol. Mae tua 5 y cant -10 y cant o doriadau yn profi oedi o undeb neu nonunion, ac mae bron pob colled asgwrn segmentol yn arwain at nonunion. Ledled y byd, perfformir mwy na 2.2 miliwn o impiadau esgyrn bob blwyddyn i drin diffygion esgyrn mewn orthopaedeg, niwrolawdriniaeth a deintyddiaeth.


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.


Fodd bynnag, mae ymarfer clinigol yn dangos nad yw'r triniaethau hyn yn ddelfrydol ac weithiau hyd yn oed yn annibynadwy. Mae cludo esgyrn trwy weithdrefn Ilizarov fel arfer yn cymryd sawl mis i wella, ac yn ystod y cyfnod hwnnw ni all y claf symud yn normal. Mae'r dull hwn hyd yn oed yn llai tebygol o gael ei ddefnyddio i drin namau ysgerbydol aml-segmentol ar yr asgwrn cefn. Mae techneg Masquelet a'r dull o impio esgyrn cortigol fasgwlaidd awtologaidd yn helpu i wella ymasiad esgyrn, ond mae'n anodd ei sefydlogi ar unwaith ar ôl llawdriniaeth. Oherwydd yr angen am lawer iawn o asgwrn allogeneig/awtologaidd fel deunydd impiad asgwrn, mae angen tynnu asgwrn llawfeddygol ychwanegol (fel tynnu asgwrn iliac) yn aml. Mae'r dull o fewnblannu'r rhwyll titaniwm yn yr ardal ddiffyg esgyrn yn darparu cyfleustra ar gyfer cymhwyso amrywiol ddeunyddiau impiad i raddau, ond mae ei effaith gosod yn gyfyngedig, ac mae ganddo hefyd ddiffygion llacio, ymsuddiant neu ddadleoli hawdd. Mewn gwirionedd, mae technegau fel Ilizarov a Masquelet hefyd yn anodd eu cymhwyso mewn rhai safleoedd daduniad, megis y metaffiseg.


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.


bloc printiau 3D mewnblaniadau titaniwm mandyllog


"Implant-bone" interface fusion


O'i gymharu â'r -dulliau uchod sy'n gofyn am lawer iawn o lenwi asgwrn allogeneig/awtologaidd, mae'n ymddangos bod manteision amlwg i gymhwyso mewnblaniadau aloi titaniwm mandyllog 3D wedi'u hargraffu i atgyweirio ac ail-greu diffygion esgyrn. Yn gyntaf, gellir addasu'r mewnblaniadau yn union yn ôl siâp y diffyg esgyrn, heb fod angen impiad asgwrn; yn ogystal, yn ôl manteision prosthesis metel, gellir dylunio dyfais sefydlogi i sicrhau sefydlogi ar unwaith rhwng y mewnblaniad ac esgyrn cyfagos, fel y gall y claf godi o'r gwely yn gynnar ar ôl llawdriniaeth; Nodweddion adeileddol mandyllog, gan ddenu meinwe asgwrn cyfagos i dyfu i mewn iddo, ac yn olaf cyflawni ymasiad parhaol o'r rhyngwyneb asgwrn mewnblaniad.

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Ffigur 1. Dadansoddiad radiolegol a biomecanyddol o fewnblaniadau Ti6A14V mandyllog printiedig 3D i ail-greu diffyg femoral 4 cm. (A) Delweddau pelydr-X 1, 3 a 6 mis ar ôl y mewnblaniad (i-iii) Delweddau tomograffeg gyfrifiadurol 1, 3 a 6 mis ar ôl y mewnblaniad (iv-vi) . Mae saethau glas yn dynodi asgwrn newydd ei ffurfio ar safle'r diffyg neu ar wyneb allanol y mewnblaniad. (vii) Sgôr radiolegol pob grŵp. (n=4) (B) Delweddau ail-greu 3D MicroCT (i-iii) o grwpiau 1, 3, a 6 mis ar ôl aberth (llwyd yn dynodi aloi titaniwm, gwyrdd yn dynodi asgwrn newydd). (iv) Canlyniadau meintiol y ffracsiwn cyfaint esgyrn yn y peri-mewnblaniad ac mewn-rhanbarthau fforwm pob grŵp (n=4).


Fodd bynnag, mae effaith therapiwtig glinigol defnyddio mewnblaniadau mandyllog printiedig 3D i atgyweirio diffygion esgyrn (yn enwedig diffygion asgwrn segment mawr) yn gofyn nid yn unig am gadarnhau canlyniadau arsylwi achosion dilynol, ond hefyd y canlyniadau astudiaethau arbrofol anifeiliaid perthnasol fel tystiolaeth. I'r perwyl hwn, cynhaliodd y tîm ymchwil-archwilio ac ymchwil manwl a systematig.

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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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Ffigur 5. Mewnblaniad Ti6Al4V mandyllog 3D wedi'i argraffu i ail-greu diffyg ffemoraidd (achos 2). X o'r nam femoral 11 cm wedi'i ail-greu yn syth ar ôl y llawdriniaeth ddiwethaf (A) a 2 (B), 5 mis (C), 8 mis (D), 14 mis (E) ac 20 mis (F) ar ôl delwedd llinell fewnblannu. Mae saethau glas yn dynodi osseointegreiddiad rhwng mewnblaniad ac asgwrn gwesteiwr.

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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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