TY - JOUR
T1 - Novel in situ gelling hydrogels loaded with recombinant collagen peptide microspheres as a slow-release system induce ectopic bone formation
AU - Fahmy-Garcia, Shorouk
AU - Mumcuoglu, Didem
AU - de Miguel, Laura
AU - Dieleman, Veerle
AU - Witte-Bouma, Janneke
AU - van der Eerden, Bram C.J.
AU - van Driel, Marjolein
AU - Eglin, David
AU - Verhaar, Jan A.N.
AU - Kluijtmans, Sebastiaan G.J.M.
AU - van Osch, Gerjo J.V.M.
AU - Farrell, Eric
N1 - © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
PY - 2018/11/7
Y1 - 2018/11/7
N2 - 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.
AB - 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.
KW - alginate
KW - BMP-2 (bone morphogenetic protein-2)
KW - bone tissue engineering
KW - hyaluronan
KW - injectable in situ gelling slow release system
UR - http://www.scopus.com/inward/record.url?scp=85053489917&partnerID=8YFLogxK
U2 - 10.1002/adhm.201800507
DO - 10.1002/adhm.201800507
M3 - Article
C2 - 30230271
VL - 7
JO - Advanced Healthcare Materials
JF - Advanced Healthcare Materials
SN - 2192-2659
IS - 21
M1 - 1800507
ER -