Abstract |
New solutions for large bone defect repair are needed. Here, in situ gelling slow release systems for bone induction are assessed. Collagen-I based Recombinant Peptide (RCP) microspheres (MSs) are produced and used as a carrier for bone morphogenetic protein 2 (BMP-2). The RCP-MSs are dispersed in three hydrogels: high mannuronate (SLM) alginate, high guluronate (SLG) alginate, and thermoresponsive hyaluronan derivative (HApN). HApN+RCP-MS forms a gel structure at 32 ºC or above, while SLM+RCP-MS and SLG+RCP-MS respond to shear stress displaying thixotropic behavior. Alginate formulations show sustained release of BMP-2, while there is minimal release from HApN. These formulations are injected subcutaneously in rats. SLM+RCP-MS and SLG+RCP-MS loaded with BMP-2 induce ectopic bone formation as revealed by X-ray tomography and histology, whereas HApN+RCP-MS do not. Vascularization occurs within all the formulations studied and is significantly higher in SLG+MS and HApN+RCP-MS than in SLM+RCP-MS. Inflammation (based on macrophage subset staining) decreases over time in both alginate groups, but increases in the HApN+RCP-MS condition. It is shown that a balance between inflammatory cell infiltration, BMP-2 release, and vascularization, achieved in the SLG+RCP-MS alginate condition, is optimal for the induction of de novo bone formation.
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Authors | Shorouk Fahmy-Garcia, Didem Mumcuoglu, Laura de Miguel, Veerle Dieleman, Janneke Witte-Bouma, Bram C J van der Eerden, Marjolein van Driel, David Eglin, Jan A N Verhaar, Sebastiaan G J M Kluijtmans, Gerjo J V M van Osch, Eric Farrell |
Journal | Advanced healthcare materials
(Adv Healthc Mater)
Vol. 7
Issue 21
Pg. e1800507
(11 2018)
ISSN: 2192-2659 [Electronic] Germany |
PMID | 30230271
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. |
Chemical References |
- Alginates
- Hydrogels
- Recombinant Proteins
- Hyaluronic Acid
- Collagen
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Topics |
- Alginates
(chemistry)
- Animals
- Bone Regeneration
(physiology)
- Collagen
(chemistry)
- Hyaluronic Acid
(chemistry)
- Hydrogels
(chemistry)
- Male
- Microspheres
- Rats
- Rats, Sprague-Dawley
- Recombinant Proteins
(genetics, metabolism)
- Tomography, X-Ray
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