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Licensed Unlicensed Requires Authentication Published by De Gruyter April 25, 2020

Developing a novel resorptive hydroxyapatite-based bone substitute for over-critical size defect reconstruction: physicochemical and biological characterization and proof of concept in segmental rabbit’s ulna reconstruction

  • Milutin Micic , Djordje Antonijevic , Sanja Milutinovic-Smiljanic , Dijana Trisic , Bozana Colovic , Dejana Kosanovic , Bogomir Prokic , Jugoslav Vasic , Slavoljub Zivkovic , Jelena Milasin , Vesna Danilovic , Marija Djuric and Vukoman Jokanovic EMAIL logo


The aim of this study was to develop novel hydroxyapatite (HAP)-based bioactive bone replacement materials for segmental osteotomy reconstruction. Customized three-dimensional (3D) bone construct was manufactured from nanohydroxyapatite (nHAP) with poly(lactide-co-glycolide) (PLGA) coating using 3D models derived from the computed tomography (CT) scanning of the rabbit’s ulna and gradient 3D printing of the bone substitute mimicking the anatomical shape of the natural bone defect. Engineered construct revealed adequate micro-architectural design for successful bone regeneration having a total porosity of 64% and an average pore size of 256 μm. Radiography and micro-CT analysis depicted new bone apposition through the whole length of the reconstructed ulna with a small area of non-resorbed construct in the central area of defect. Histological analysis revealed new bone formation with both endochondral and endesmal type of ossification. Immunohistochemistry analysis depicted the presence of bone formation indicators – bone morphogenetic protein (BMP), osteocalcin (OCN) and osteopontin (OPN) within newly formed bone. Manufactured personalized construct acts as a “smart” responsive biomaterial capable of modulating the functionality and potential for the personalized bone reconstruction on a clinically relevant length scale.

  1. Author statement

  2. Funding: The work was supported by Ministry of Education and Science of the Republic of Serbia (Funder Id:; grant numbers 172026 and III 45005).

  3. Conflict of interest: Authors state no conflict of interest.

  4. Informed consent: Informed consent is not applicable.

  5. Ethical approval: The conducted research is approved by relevant institutions.


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Supplementary Material

The online version of this article offers supplementary material (

Received: 2019-08-20
Accepted: 2019-12-09
Published Online: 2020-04-25
Published in Print: 2020-08-27

©2020 Walter de Gruyter GmbH, Berlin/Boston

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