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Novel In Situ Gelling Hydrogels Loaded with Recombinant Collagen Peptide Microspheres as a Slow‐Release System Induce Ectopic Bone Formation
Author(s) -
FahmyGarcia Shorouk,
Mumcuoglu Didem,
de Miguel Laura,
Dieleman Veerle,
WitteBouma Janneke,
van der Eerden Bram C. J.,
van Driel Marjolein,
Eglin David,
Verhaar Jan A. N.,
Kluijtmans Sebastiaan G. J. M.,
van Osch Gerjo J. V. M.,
Farrell Eric
Publication year - 2018
Publication title -
advanced healthcare materials
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.288
H-Index - 90
eISSN - 2192-2659
pISSN - 2192-2640
DOI - 10.1002/adhm.201800507
Subject(s) - self healing hydrogels , bone morphogenetic protein 2 , chemistry , thixotropy , in situ , peptide , recombinant dna , bone morphogenetic protein , inflammation , biophysics , biomedical engineering , materials science , in vitro , biochemistry , immunology , polymer chemistry , medicine , biology , organic chemistry , composite material , gene
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.