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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Seotud uurimistööd, mis on avaldatud ajakirjas 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
Traumast, infektsioonist või kasvaja resektsioonist tingitud suured segmentaalsed luudefektid on alati olnud keeruline kliiniline probleem. Umbes 5–10 protsendil luumurdudest esineb hilinenud liitumine või mitteliitmine ning peaaegu kogu segmentaalne luukadu põhjustab mitteliitumist. Kogu maailmas tehakse ortopeedias, neurokirurgias ja hambaravis luudefektide raviks aastas üle 2,2 miljoni luusiirdamise.
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.
Kuid kliiniline praktika näitab, et need ravimeetodid ei ole ideaalsed ja mõnikord isegi ebausaldusväärsed. Luu transport Ilizarovi protseduuri kaudu võtab paranemiseks tavaliselt mitu kuud, mille jooksul patsient ei saa normaalselt liikuda. Seda meetodit kasutatakse veelgi vähem tõenäoliselt mitmesegmendiliste lülisamba{0}}skeleti defektide raviks. Masquelet' tehnika ja autoloogse vaskulariseeritud kortikaalse luu siirdamise meetod aitavad tugevdada luu sulandumist, kuid kohest operatsioonijärgset stabiliseerimist on raske saavutada. Kuna luutransplantaadi materjalina on vaja kasutada suurt hulka allogeenset/autoloogset luud, on sageli vajalik täiendav kirurgiline luu eemaldamine (näiteks niudeluu eemaldamine). Titaanvõrgu luudefekti piirkonda siirdamise meetod pakub teatud määral mugavust erinevate transplantaadimaterjalide pealekandmiseks, kuid selle fikseeriv toime on piiratud ning puuduseks on ka kerge lahtitulek, vajumine või nihkumine. Tegelikult on selliseid tehnikaid nagu Ilizarov ja Masquelet raske rakendada ka teatud dissotsiatsioonikohtades, näiteks metafüüsis.
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.
plokk 3D prindib poorseid titaanimplantaate
"Implant-bone" interface fusion
Võrreldes ülalnimetatud-meetoditega, mis nõuavad suurt hulka allogeenset/autoloogset luutäitmist, näib 3D-prinditud poorse titaanisulamist implantaatide kasutamine luudefektide parandamiseks ja rekonstrueerimiseks ilmseid eeliseid. Esiteks saab implantaate täpselt kohandada vastavalt luudefekti kujule, ilma et oleks vaja luusiirdamist; lisaks saab vastavalt metallproteesi eelistele konstrueerida fikseerimisseadme, et saavutada kohene stabiliseerimine implantaadi ja külgnevate luude vahel, et patsient saaks pärast operatsiooni varakult voodist tõusta; Poorsed struktuuriomadused, mis meelitavad külgnevat luukoe sellesse kasvama ja lõpuks saavutavad implantaadi -luu liidese püsiva sulandumise.
Joonis 1. 3D-prinditud poorsete Ti6A14V implantaatide radioloogiline ja biomehaaniline analüüs 4 cm reieluu defekti rekonstrueerimiseks. (A) Röntgenpildid 1, 3 ja 6 kuud pärast implanteerimist (i-iii) Kompuutertomograafia kujutised 1, 3 ja 6 kuud pärast implanteerimist (iv{13}}vi) . Sinised nooled näitavad äsja moodustunud luud defekti kohas või implantaadi välispinnal. (vii) Iga rühma radioloogiline skoor. (n=4) (B) MicroCT 3D-rekonstruktsiooni kujutised (i-iii) rühmadest 1, 3 ja 6 kuud pärast ohverdamist (hall tähistab titaanisulamit, roheline tähistab uut luu). (iv) Luumahu fraktsiooni kvantitatiivsed tulemused iga rühma peri-implantaadi ja in-i foram piirkondades (n=4).
3D-prinditud poorsete implantaatide kasutamise kliiniline terapeutiline toime luudefektide (eriti suurte-segmentide luudefektide) parandamiseks nõuab aga mitte ainult jälgimisjuhtumite vaatlustulemuste kinnitamist, vaid ka tõenditena asjakohaste loomkatsete tulemused. Sel eesmärgil viis uurimisrühm läbi-süstemaatilise uurimise ja uurimistöö.
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.
Joonis 5. 3D-prinditud poorne Ti6Al4V implantaat reieluu defekti rekonstrueerimiseks (juhtum 2). X rekonstrueeritud 11 cm reieluu defektist vahetult pärast viimast operatsiooni (A) ja 2 (B), 5 kuud (C), 8 kuud (D), 14 kuud (E) ja 20 kuud (F) pärast implantatsioonijoone kujutist. Sinised nooled näitavad osseointegratsiooni implantaadi ja peremeesluu vahel.
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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