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doctoral thesis
Indukcija ektopičnog koštanog tkiva osteoinduktivnim implantatom koji sadrži rekombinirani humani koštani morfogenetski protein 6 (rhBMP6), autologni krvni ugrušak i bifazičnu biokeramiku
Zagreb: University of Zagreb, School of Medicine, 2022. urn:nbn:hr:105:946766
Štoković, Nikola
University of Zagreb
School of Medicine

Institutional repository: Dr Med - University of Zagreb School of Medicine Digital Repository

Cite this document

Štoković, N. (2022). Indukcija ektopičnog koštanog tkiva osteoinduktivnim implantatom koji sadrži rekombinirani humani koštani morfogenetski protein 6 (rhBMP6), autologni krvni ugrušak i bifazičnu biokeramiku (Doctoral thesis). Zagreb: University of Zagreb, School of Medicine. Retrieved from https://urn.nsk.hr/urn:nbn:hr:105:946766

Štoković, Nikola. "Indukcija ektopičnog koštanog tkiva osteoinduktivnim implantatom koji sadrži rekombinirani humani koštani morfogenetski protein 6 (rhBMP6), autologni krvni ugrušak i bifazičnu biokeramiku." Doctoral thesis, University of Zagreb, School of Medicine, 2022. https://urn.nsk.hr/urn:nbn:hr:105:946766

Štoković, Nikola. "Indukcija ektopičnog koštanog tkiva osteoinduktivnim implantatom koji sadrži rekombinirani humani koštani morfogenetski protein 6 (rhBMP6), autologni krvni ugrušak i bifazičnu biokeramiku." Doctoral thesis, University of Zagreb, School of Medicine, 2022. https://urn.nsk.hr/urn:nbn:hr:105:946766

Štoković, N. (2022). 'Indukcija ektopičnog koštanog tkiva osteoinduktivnim implantatom koji sadrži rekombinirani humani koštani morfogenetski protein 6 (rhBMP6), autologni krvni ugrušak i bifazičnu biokeramiku', Doctoral thesis, University of Zagreb, School of Medicine, accessed 25 November 2024, https://urn.nsk.hr/urn:nbn:hr:105:946766

Štoković N. Indukcija ektopičnog koštanog tkiva osteoinduktivnim implantatom koji sadrži rekombinirani humani koštani morfogenetski protein 6 (rhBMP6), autologni krvni ugrušak i bifazičnu biokeramiku [Doctoral thesis]. Zagreb: University of Zagreb, School of Medicine; 2022 [cited 2024 November 25] Available at: https://urn.nsk.hr/urn:nbn:hr:105:946766

N. Štoković, "Indukcija ektopičnog koštanog tkiva osteoinduktivnim implantatom koji sadrži rekombinirani humani koštani morfogenetski protein 6 (rhBMP6), autologni krvni ugrušak i bifazičnu biokeramiku", Doctoral thesis, University of Zagreb, School of Medicine, Zagreb, 2022. Available at: https://urn.nsk.hr/urn:nbn:hr:105:946766

Metadata
TitleIndukcija ektopičnog koštanog tkiva osteoinduktivnim implantatom koji sadrži rekombinirani humani koštani morfogenetski protein 6 (rhBMP6), autologni krvni ugrušak i bifazičnu biokeramiku
Title (english)Ectopic bone induction by osteoinductive device composed of recombinant human bone morphogenetic protein 6 (rhBMP6), autologous blood coagulum and biphasic bioceramics
AuthorNikola Štoković
MentorSlobodan Vukičević (mentor)
Committee memberMarko Pećina (predsjednik povjerenstva)
Committee memberSven Seiwerth (član povjerenstva)
Committee memberDomagoj Delimar (član povjerenstva)
GranterUniversity of Zagreb
School of Medicine
Zagreb
Defense date and country2022-02-09, 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
Keywords (english)
Languagecroatian
URN:NBNurn:nbn:hr:105:946766
ProjectNumber: 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 programmeTitle: 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 resourceText
Extent104 str.
File originBorn digital
Access conditionsOpen access
Terms of useLicence In copyright icon
Created on2022-03-31 08:20:24