Bone morphogenetic proteins: From discovery to development of a novel autologous bone graft substitute consisting of recombinant human BMP6 delivered in autologous blood coagulum carrier
| العنوان: | Bone morphogenetic proteins: From discovery to development of a novel autologous bone graft substitute consisting of recombinant human BMP6 delivered in autologous blood coagulum carrier |
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| المؤلفون: | Vukičević, Slobodan, Perić, Mihaela, Oppermann, Hermann, Štoković, Nikola, Ivanjko, Natalia, Erjavec, Igor, Kufner, Vera, Vnuk, Dražen, Bubić-Špoljar, Jadranka, Pećin, Marko, Novak, Ruđer, Matić Jelić, Ivona, Bakić, Kristina, Milešević, Marina, Blažević, Viktorija, Rogina, Lucija, Vikić-Topić, Smiljka, Božić, Tamara, Verbanac, Donatella, Bordukalo Nikšić, Tatjana, Sampath, T Kuber, Pećina, Marko, Matičić, Dražen, Grgurević, Lovorka |
| المصدر: | Rad Hrvatske akademije znanosti i umjetnosti. Medicinske znanosti Volume . Issue 544 =52-53 |
| بيانات النشر: | Croatian Academy of Sciences and Arts, 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | BMP6, TGFβ superfamily, endochondral bone formation, bone mimetic, distal radial fracture, high tibial osteotomy, posterolateral lumbar spine fusion, allograft, chronic lumbar back pain, regenerative medicine, BMP6, TGFβ nadobitelj, endohondralno stvaranje kosti, koštani mimetik, dis- talni prijelom radijusa, visoka osteotomija tibije, posteorolateralna spinalna fuzija, alograft, kronična slabinska bol, regenerativna medicina |
| الوصف: | Bone Morphogenetic Proteins (BMPs) are growth and differentiation factors within the TGFβ superfam- ily of proteins. They induce ectopic and orthotopic endochondral bone formation and are involved in the regulation of cell proliferation, differentiation, apoptosis and mesenchymal-epithelial interactions in critical morphogenetic processes of tissues beyond bone. BMP2 and BMP7 osteogenic devices have been approved for enhancing healing in patients with long bone defects and anterior spinal fusion proce- dures. However, due to a high price and various serious adverse events including heterotopic ossifica- tion, retrograde ejaculation and pain their clinical use have been limited. In this review we discuss the BMP discovery, biology and their use in clinical studies with particular reference to the newly developed BMP6 based autologous bone graft substitute (ABGS). A novel ABGS consisting of an autologous bone coagulum (ABC) carrier with dispersed BMP6 to initiate the differentiation of mesenchymal cells into endochondral bone. The ABC met the conditions for an optimal delivery system for BMP6 due to han- dling simplicity, without an immunogenic and inflammatory response at the implantation site. Addition of allograft or synthetic ceramics to ABGS demonstrated in animal models significantly increased volume and better microarchitecture of the newly formed bone. The first clinical study was conducted in patients with distal radial fractures (Phase I study) and the second in patients undergoing high tibial osteotomy (Phase I/II study) and no serious adverse events have been observed. Finally, in the ongoing OSTEO- proSPINE study ABGS enforced with allograft bone is evaluated in patients with chronic back pain due to degenerative disc diseases. The novel ABGS bone mimetic is a major breakthrough and contribution to bone biology and regenerative medicine of skeletal repair. Koštani morfogenetski proteini (BMP) čine grupu čimbenika rasta i diferencijacije unutar TGFβ nado- bitelji. Oni induciraju stvaranje ektopične i ortotopične endohondralne kosti te su uključeni u regulaciju stanične proliferacije, diferencijacije, apoptoze i mezenhimalno-epitelne interakcije u važnim tkivnim morfogenetskim procesima izvan koštanog sustava. Koštane naprave koje sadrže BMP2 i BMP7 pro- tein odobrene su za poboljšanje koštanog cijeljenja kod pacijenata s defektima dugih cjevastih kostiju i kod prednje spinalne fuzije kralježnice. Međutim, zbog visoke cijene i mnogobrojnih nuspojava koje su uključivale pojavu heterotopičnih osifikacija, retrogradnu ejakulaciju i bol, njihova je klinička prim- jena ograničena. U ovom smo preglednom radu raspravili otkriće BMP molekula, njihovu biologiju i primjenu u kliničkim studijama s posebnim osvrtom na nedavno otkrivenu novu autolognu koštanu napravu (ABGS) koja sadrži BMP6. Novi ABGS sastoji se od nosača autolognog koaguluma (ABC) s otopljenim BMP6 koji je ključan za pokretanje diferencijacije mezenhimalnih stanica u smjeru stvaranja endohondralne kosti. ABC je ispunio sve potrebne uvjete za formulaciju optimalnog nosača za BMP6 isključivo zbog jednostavnosti priprave i primjene te odsustva imunogenog i upalnog odgovora na mjestu implantacije. Uz dodatak alografta ili sintetičke keramike što je potvrđeno na životinjskim modelima došlo je do značajnog povećanja volumena te poboljšanja mikroarhitekture novonastale kosti. Prvo kliničko ispitivanje provedeno je na pacijentima s distalnim prijelomima radijusa (faza I studije), a drugo na pacijentima koji su podvrgnuti visokoj osteotomiji tibije (faza I/II studije) bez uočenih ozbiljnih nuspojava. Trenutno je u tijeku studija OSTEOproSPINE u kojoj se testira učinkovitost ABGS u kom- binaciji s koštanim alograftom u bolesnika s kroničnim bolovima u leđima uzrokovanim degenerativnim promjenama intervertebralnog diska. Nova ABGS koštana naprava značajna je prekretnica i napredak u području koštane biologije te regenerativne medicine koštanog sustava. |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 1848-641X 1330-5301 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=od_______951::b76046d284730e5e88878dff56c903e0 https://hrcak.srce.hr/248880 |
| Rights: | OPEN |
| رقم الانضمام: | edsair.od.......951..b76046d284730e5e88878dff56c903e0 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 1848641X 13305301 |
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