Bone extracts immunomodulate and enhance the regenerative performance of dicalcium phosphates bioceramics

被引：41

作者：

Mansour, Alaa ^{[1
]}

Abu-Nada, Lina ^{[1
]}

Al-Waeli, Haider ^{[1
]}

Mezour, Mohamed Amine ^{[1
]}

Abdallah, Mohamed-Nur ^{[1
]}

Kinsella, Joseph M. ^{[2
]}

Kort-Mascort, Jacqueline ^{[2
]}

Henderson, Janet E. ^{[3
,4
]}

Ramirez-Garcialuna, Jose Luis ^{[3
,4
]}

Tran, Simon D. ^{[1
]}

Elkashty, Osama A. ^{[3
,5
]}

Mousa, Aisha ^{[1
]}

El-hadad, Amir A. ^{[1
]}

Taqi, Doaa ^{[1
]}

Al-Hamad, Faez ^{[1
]}

Alageel, Omar ^{[1
,6
]}

Kaartinen, Mari T. ^{[1
]}

Tamimi, Faleh ^{[1
]}

机构：

[1] McGill Univ, Fac Dent, Montreal, PQ, Canada

[2] McGill Univ, Dept Bioengn, Fac Engn, Montreal, PQ, Canada

[3] McGill Univ, Fac Med, Montreal, PQ, Canada

[4] McGill Univ, Ctr Hlth, Bone Engn Labs, Res Inst, Montreal, PQ, Canada

[5] Mansoura Univ, Fac Dent, Mansoura, Egypt

[6] King Saud Univ, Coll Appl Med Sci, Riyadh, Saudi Arabia

来源：

ACTA BIOMATERIALIA | 2019年 / 89卷

基金：

加拿大自然科学与工程研究理事会;

关键词：

Bioceramics; Bone extracellular matrix extracts; Immune system; Bone regeneration; 3D-printing; BODY GIANT-CELLS; MATRIX PROTEINS; M2; MACROPHAGES; IN-VIVO; IMPLANT OSSEOINTEGRATION; IMMUNE-RESPONSE; GENE-EXPRESSION; GROWTH-FACTOR; ACTIVATION; ADSORPTION;

D O I：

10.1016/j.actbio.2019.03.012

中图分类号：

R318 [生物医学工程];

学科分类号：

0831 ;

摘要：

Immunomodulation strategies are believed to improve the integration and clinical performance of synthetic bone substitutes. One potential approach is the modification of biomaterial surface chemistry to mimic bone extracellular matrix (ECM). In this sense, we hypothesized that coating synthetic dicalcium phosphate (DCP) bioceramics with bone ECM proteins would modulate the host immune reactions and improve their regenerative performance. To test this, we evaluated the in vitro proteomic surface interactions and the in vivo performance of ECM-coated bioceramic scaffolds. Our results demonstrated that coating DCP scaffolds with bone extracts, specifically those containing calcium-binding proteins, dramatically modulated their interaction with plasma proteins in vitro, especially those relating to the innate immune response. In vivo, we observed an attenuated inflammatory response against the bioceramic scaffolds and enhanced peri-scaffold new bone formation supported by the increased osteoblastogenesis and reduced osteoclastogenesis. Furthermore, the bone extract rich in calcium-binding proteins can be 3D-printed to produce customized hydrogels with improved regeneration capabilities. In summary, bone extracts containing calcium-binding proteins can enhance the integration of synthetic biomaterials and improve their ability to regenerate bone probably by modulating the host immune reaction. This finding helps understand how bone allografts regenerate bone and opens the door for new advances in tissue engineering and bone regeneration. Statement of Significance Foreign-body reaction is an important determinant of in vivo biomaterial integration, as an undesired host immune response can compromise the performance of an implanted biomaterial. For this reason, applying immunomodulation strategies to enhance biomaterial engraftment is of great interest in the field of regenerative medicine. In this article, we illustrated that coating dicalcium phosphate bioceramic scaffolds with bone-ECM extracts, especially those rich in calcium-binding proteins, is a promising approach to improve their surface proteomic interactions and modulate the immune responses towards such biomaterials in a way that improves their bone regeneration performance. Collectively, the results of this study may provide a conceivable explanation for the mechanisms involved in presenting the excellent regenerative efficacy of natural bone grafts. (C) 2019 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

引用

页码：343 / 358

页数：16

共 107 条

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