Novel in situ gelling hydrogels loaded with recombinant collagen peptide microspheres as a slow-release system induce ectopic bone formation

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

Research output: Contribution to journalArticleAcademicpeer-review

2 Citations (Scopus)

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.

Original languageEnglish
Article number1800507
Number of pages14
JournalAdvanced Healthcare Materials
Volume7
Issue number21
Early online date19 Sep 2018
DOIs
Publication statusPublished - 7 Nov 2018

Keywords

  • alginate
  • BMP-2 (bone morphogenetic protein-2)
  • bone tissue engineering
  • hyaluronan
  • injectable in situ gelling slow release system

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