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Novel In Situ Gelling Hydrogels Loaded with Recombinant Collagen Peptide Microspheres as a Slow-Release System Induce Ectopic Bone Formation.

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.
AuthorsShorouk 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
JournalAdvanced healthcare materials (Adv Healthc Mater) Vol. 7 Issue 21 Pg. e1800507 (11 2018) ISSN: 2192-2659 [Electronic] Germany
PMID30230271 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Copyright© 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
Chemical References
  • Alginates
  • Hydrogels
  • Recombinant Proteins
  • Hyaluronic Acid
  • Collagen
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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