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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Sorodni raziskovalni članki, objavljeni v reviji 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
Velike segmentne okvare kosti zaradi travme, okužbe ali resekcije tumorja so bile vedno izziv klinični problem. Pri približno 5 do 10 odstotkih zlomov pride do zapoznelega združitve ali nezrasla, skoraj vsa segmentna izguba kosti pa povzroči nezraščanje. Po vsem svetu se letno izvede več kot 2,2 milijona kostnih presadkov za zdravljenje kostnih okvar v ortopediji, nevrokirurgiji in zobozdravstvu.
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.
Vendar klinična praksa kaže, da ta zdravljenja niso idealna in včasih celo nezanesljiva. Prevoz kosti po Ilizarovem postopku običajno traja več mesecev, da se zaceli, v tem času pa se bolnik ne more normalno premikati. Še manj verjetno je, da se ta metoda uporablja za zdravljenje več-segmentnih skeletnih okvar hrbtenice. Masqueletova tehnika in metoda avtologne vaskularizirane kortikalne kostne presaditve pripomoreta k izboljšanju fuzije kosti, vendar je težko doseči takojšnjo pooperativno stabilizacijo. Zaradi potrebe po veliki količini alogenske/avtologne kosti kot materiala za kostni presadek je pogosto potrebna dodatna kirurška odstranitev kosti (kot je odstranitev iliakalne kosti). Metoda implantacije titanove mreže v območje kostne defekte do določene mere omogoča udobje za nanos različnih presadnih materialov, vendar je njen fiksacijski učinek omejen, poleg tega pa ima tudi pomanjkljivosti lahkega rahljanja, posedanja ali premikanja. Pravzaprav je tehnike, kot sta Ilizarov in Masquelet, težko uporabiti tudi na določenih mestih disociacije, kot je metafiza.
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 3D natisne porozne titanove vsadke
"Implant-bone" interface fusion
V primerjavi z zgoraj-omenjenimi metodami, ki zahtevajo veliko alogenskega/avtolognega kostnega polnjenja, se zdi, da ima uporaba 3D-natisnjenih poroznih vsadkov iz titanove zlitine za popravilo in rekonstrukcijo kostnih napak očitne prednosti. Prvič, implantate je mogoče natančno prilagoditi glede na obliko kostne napake, brez potrebe po kostnem presadku; poleg tega je glede na prednosti kovinske proteze mogoče oblikovati fiksacijsko napravo za doseganje takojšnje stabilizacije med vsadkom in sosednjimi kostmi, tako da lahko pacient zgodaj vstane iz postelje po operaciji; Porozne strukturne značilnosti, ki pritegnejo sosednje kostno tkivo, da zraste vanj, in končno doseže trajno zlitje vsadka-kostnega vmesnika.
Slika 1. Radiološka in biomehanska analiza 3D tiskanih poroznih vsadkov Ti6A14V za rekonstrukcijo 4 cm defekta stegnenice. (A) Rentgenske slike 1, 3 in 6 mesecev po implantaciji (i-iii) Slike računalniške tomografije 1, 3 in 6 mesecev po implantaciji (iv-vi) . Modre puščice kažejo na novo oblikovano kost na mestu okvare ali na zunanji površini vsadka. (vii) radiološki rezultat vsake skupine. (n=4) (B) MicroCT 3D rekonstrukcijske slike (i-iii) skupin 1, 3 in 6 mesecev po žrtvovanju (siva označuje titanovo zlitino, zelena označuje novo kost). (iv) Kvantitativni rezultati deleža volumna kosti v peri-vsadku in v-območjih foram vsake skupine (n=4).
Vendar pa klinični terapevtski učinek uporabe 3D natisnjenih poroznih vsadkov za popravilo kostnih napak (zlasti defektov velikih-segmentov kosti) zahteva ne le potrditev rezultatov opazovanja-nadaljnjih primerov, temveč tudi rezultati ustreznih poskusnih študij na živalih kot dokaz. V ta namen je raziskovalna skupina izvedla-poglobljeno in sistematično raziskovanje in raziskovanje.
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.
Slika 5. 3D-natisnjen porozni implantat Ti6Al4V za rekonstrukcijo defekta stegnenice (primer 2). X rekonstruirane 11 cm defekte stegnenice takoj po zadnji operaciji (A) in 2 (B), 5 mesecev (C), 8 mesecev (D), 14 mesecev (E) in 20 mesecev (F) po sliki linije implantacije. Modre puščice označujejo oseointegracijo med vsadkom in gostiteljsko kostjo.
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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