Mechanistic Illustration: How Newly-Formed Blood Vessels Stopped by the Mineral Blocks of Bone Substitutes Can Be Avoided by Using Innovative Combined Therapeutics

被引：8

作者：

Bornert, Fabien ^{[1
,2
,3
]}

Clauss, Francois ^{[1
,2
,3
]}

Hua, Guoqiang ^{[1
,2
]}

Idoux-Gillet, Ysia ^{[1
,2
]}

Keller, Laetitia ^{[1
,2
]}

De Grado, Gabriel Fernandez ^{[1
,2
,3
]}

Offner, Damien ^{[1
,2
,3
]}

Smaida, Rana ^{[1
,2
]}

Wagner, Quentin ^{[1
,2
]}

Fioretti, Florence ^{[1
,2
,3
]}

Kuchler-Bopp, Sabine ^{[1
,2
]}

Schulz, Georg ^{[4
]}

Wenzel, Wolfgang ^{[5
]}

Gentile, Luca ^{[1
,2
]}

Risser, Laurent ^{[6
]}

Mueller, Bert ^{[4
]}

Huck, Olivier ^{[1
,2
,3
]}

Benkirane-Jessel, Nadia ^{[1
,2
,3
]}

机构：

[1] INSERM French Natl Inst Hlth & Med Res, CRBS, UMR 1260, Regenerat Nanomed, 1 Rue Eugene Boeckel, F-67000 Strasbourg, France

[2] Univ Strasbourg, Univ Hosp Strasbourg HUS, Fac Dent Surg, 8 Rue St Elisabeth, F-67000 Strasbourg, France

[3] Univ Hosp Strasbourg HUS, Dept Pediat Dent, 1 Pl Hop, F-67000 Strasbourg, France

[4] Univ Basel, Biomat Sci Ctr, Gewerbestr 14, CH-4123 Allschwil, Switzerland

[5] Karlsruhe Inst Technol, Inst Nanotechnol, Campus North,Bldg 640, DE-76131 Karlsruhe, Germany

[6] Univ Toulouse, Toulouse Inst Math, UMR 5219, CNRS UPS IMT, F-31062 Toulouse, France

来源：

BIOMEDICINES | 2021年 / 9卷 / 08期

关键词：

therapeutic bone filling; pro-angiogenic smart nanotechnology; hybrid bone substitute; smart nano-active complexes; MESENCHYMAL STEM-CELLS; CALCIUM-PHOSPHATE CERAMICS; HEPARIN-BINDING DOMAIN; GROWTH-FACTOR VEGF; ENDOTHELIAL-CELLS; PROMOTES VASCULARIZATION; BASIC SCIENCE; TISSUE; REGENERATION; DEFECT;

D O I：

10.3390/biomedicines9080952

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

070307 [化学生物学]; 071010 [生物化学与分子生物学];

摘要：

One major limitation for the vascularization of bone substitutes used for filling is the presence of mineral blocks. The newly-formed blood vessels are stopped or have to circumvent the mineral blocks, resulting in inefficient delivery of oxygen and nutrients to the implant. This leads to necrosis within the implant and to poor engraftment of the bone substitute. The aim of the present study is to provide a bone substitute currently used in the clinic with suitably guided vascularization properties. This therapeutic hybrid bone filling, containing a mineral and a polymeric component, is fortified with pro-angiogenic smart nano-therapeutics that allow the release of angiogenic molecules. Our data showed that the improved vasculature within the implant promoted new bone formation and that the newly-formed bone swapped the mineral blocks of the bone substitutes much more efficiently than in non-functionalized bone substitutes. Therefore, we demonstrated that our therapeutic bone substitute is an advanced therapeutical medicinal product, with great potential to recuperate and guide vascularization that is stopped by mineral blocks, and can improve the regeneration of critical-sized bone defects. We have also elucidated the mechanism to understand how the newly-formed vessels can no longer encounter mineral blocks and pursue their course of vasculature, giving our advanced therapeutical bone filling great potential to be used in many applications, by combining filling and nano-regenerative medicine that currently fall short because of problems related to the lack of oxygen and nutrients.

引用

页数：19

共 75 条

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