Indukcija ektopičnog koštanog tkiva osteoinduktivnim implantatom koji sadrži rekombinirani humani koštani morfogenetski protein 6 (rhBMP6), autologni krvni ugrušak i bifazičnu biokeramiku

doctoral thesis

• Title (english): Ectopic bone induction by osteoinductive device composed of recombinant human bone morphogenetic protein 6 (rhBMP6), autologous blood coagulum and biphasic bioceramics
• Author: Nikola Štoković
• Mentor: Slobodan Vukičević (mentor)
• Committee member: Marko Pećina (predsjednik povjerenstva)
• Committee member: Sven Seiwerth (član povjerenstva)
• Committee member: Domagoj Delimar (član povjerenstva)
• Granter: University of Zagreb; School of Medicine; Zagreb
• Defense date and country: 2022-02-09, Croatia
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Basic Medical Sciences; Anatomy
• Universal decimal classification (UDC): 611 - Anatomy

Abstract

Osteoinduktivni lijek koji sadrži rekombinantni humani koštani morfogenetski protein 6 (rhBMP6) u autolognom krvnom ugrušku (ABC) s biokeramičkim česticama, nova je terapijska opcija za postizanje spinalne fuzije i liječenje segmentalnih defekata dugih kostiju. U sklopu ovog rada istražena je biologija i vremenski tijek ektopičnog stvaranja koštanog tkiva pod utjecajem rhBMP6 u ABC-u s biokeramičkim česticama različite veličine (74-420 μm, 500-1700 μm i 2360-4000 μm) na modelu subkutane ugradnje implantata u štakora. Time je dokazana sigurnost i efikasnost osteoinduktivnog lijeka na modelu posterolateralne spinalne fuzije (PLF) kod kunića. Biokeramičke čestice promoviraju stvaranje kosti pod utjecajem rhBMP6 u subkutanom eseju kod štakora, a veličina čestica determinira mehanizam osifikacije, strukturu i dugotrajnost kosti. U implantatima s malim biokeramičkim česticama koje imaju veliku površinu i male udaljenosti između čestica, kost nastaje predominantno intramembranozno, a u implantatima sa srednjim i velikim česticama predominantno endokondralno. Novostvorena koštano-keramička struktura s malim česticama sastoji se od gustog koštanog tkiva na površini i između čestica, s limitiranom koštanom srži te se njegova struktura ne mijenja u vremenu. Koštano-keramička struktura sa srednjim i velikim česticama sastoji se od kortikalne kosti i kosti na površini čestica koje su postojane u vremenu, te trabekula između čestica čija se debljina smanjuje u vremenu. U modelu PLF-a kod kunića dokazano je da osteoinduktivni lijek (rhBMP6/ABC) s biokeramičkim česticama inducira stvaranje kosti koja se uspješno fuzionira s nativnim transverzalnim nastavcima. Navedena je spoznaja polazna točka za daljnja istraživanja kojima je cilj razvoj lijeka za kliničku primjenu.

Abstract (english)

Osteoinductive device comprised of recombinant human Bone Morphogenetic Protein 6 (rhBMP6) in autologous blood coagulum (ABC) with bioceramic particles is a novel therapeutic solution for spinal fusions and management of segmental bone defects. In this study we elucidated biology and time course of ectopic bone formation induced by rhBMP6 in ABC with bioceramic particles of different sizes (74-420 μm, 500-1700 μm and 2360-4000 μm) using rat subcutaneous implant assay. Moreover, we have proven safety and efficacy of osteoinductive device in rabbit PLF model. Bioceramic particles promoted rhBMP6 mediated bone formation in rat subcutaneous assay while particle size determined mechanism of ossification, structure and longevity of newly formed bone. In implants containing small particles which are characterized by large surfaces and small distances between the particles, bone was predominantly formed through intramembranous pathway while in implants containing medium and large ceramics bone was predominantly formed endochondrally. Newly formed bone-ceramic structure (BCS) with small particles contained dense bone between the particles and its structure was constant in time. BCS with medium and large particles contained cortical bone and bone at the surfaces of particles which were constant in time and trabeculae between the particles which decreased in time. In the rabbit PLF model it was demonstrated that osteoinductive device (rhBMP6/ABC) with bioceramic particles induces bone formation and osseointegration with native transverse processes. Findings of this study will be the basis for further research aimed to developing a drug for clinical use.

• Keywords: koštano tkivo; osteoinduktivni implant; koštani morfogenetski protein 6; osteogenesis
• Keywords (english): bone tissue; osteoinductive implant; bone morphogenetic protein 6; osteogenesis
• Language: croatian
• URN:NBN: urn:nbn:hr:105:946766
• Project: Number: KK.01.1.1.01.0008; Title: Znanstveni centar izvrsnosti za reproduktivnu i regenerativnu medicinu – istraživanja novih platformi i potencijala; Title: Reproductive, and Regenerative Medicine-Exploring New Platforms and Potentials; Acronym: CERRM; Leader: Slobodan Vukičević; Jurisdiction: eu; Funder: EK
• Study programme: Title: Biomedicine and Health Sciences; Study programme type: university; Study level: postgraduate; Academic / professional title: doktor/doktorica znanosti, područje biomedicine i zdravstvo (doktor/doktorica znanosti, područje biomedicine i zdravstvo)
• Type of resource: Text
• Extent: 104 str.
• File origin: Born digital
• Access conditions: Open access
• Created on: 2022-03-31 08:20:24