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Tissue Eng Part A. 2020 Feb 11. doi: 10.1089/ten.TEA.2019.0310. [Epub ahead of print]

Alginate Hydrogels for In Vivo Bone Regeneration: The Immune Competence of the Animal Model Matters.

Author information

1
Charité Universitätsmedizin Berlin, 14903, Julius Wolff Institute & Center for Musculoskeletal Surgery, Berlin, Berlin, Germany.
2
Max Planck Institute of Colloids and Interfaces, 28321, Department of Biomaterials, Potsdam, Brandenburg, Germany; Daniela.Garske@mpikg.mpg.de.
3
Charité Universitätsmedizin Berlin, 14903, Julius Wolff Institute & Center for Musculoskeletal Surgery, Berlin, Berlin, Germany; katharina.schmidt-bleek@charite.de.
4
Charité Universitätsmedizin Berlin, 14903, Julius Wolff Institute & Center for Musculoskeletal Surgery, Berlin, Berlin, Germany; agnes.ellinghaus@charite.de.
5
Charité Universitätsmedizin Berlin, 14903, Berlin-Brandenburg Center for Regenerative Therapies, Berlin, Berlin, Germany; Anke.Dienelt@gmx.de.
6
Harvard University, 1812, School of Engineering and Applied Sciences, Cambridge, Massachusetts, United States.
7
Harvard University, 1812, Wyss Institute for Biologically Inspired Engineering, Cambridge, Massachusetts, United States.
8
Johns Hopkins University, 1466, Department of Materials Science and Engineering, Baltimore, Maryland, United States; luogu@jhu.edu.
9
Harvard University, School of Engineering and Applied Sciences, Cambridge, Massachusetts, United States.
10
Harvard University, 1812, Wyss Institute for Biologically Inspired Engineering, Cambridge, Massachusetts, United States; mooneyd@seas.harvard.edu.
11
Charité - Universitätsmedizin Berlin, Julius Wolff Institut and Center for Musculoskeletal Surgery, Berlin, Germany.
12
Charité Universitätsmedizin Berlin, 14903, Berlin-Brandenburg Center for Regenerative Therapies, Berlin, Berlin, Germany; Georg.Duda@Charite.de.
13
Max Planck Institute of Colloids and Interfaces, 28321, Department of Biomaterials, Potsdam, Brandenburg, Germany.
14
Charité Universitätsmedizin Berlin, 14903, Berlin-Brandenburg Center for Regenerative Therapies, Berlin, Berlin, Germany; amaia.cipitria@mpikg.mpg.de.

Abstract

Biomaterials with tunable biophysical properties hold great potential for tissue engineering. The adaptive immune system plays an important role in bone regeneration. Our goal is to investigate the regeneration potential of cell-laden alginate hydrogels depending on the immune status of the animal model. Specifically, the regeneration potential of rat mesenchymal stromal cell (MSC)-laden, void-forming alginate hydrogels, with a stiffness optimized for osteogenic differentiation, is studied in 5 mm critical-sized femoral defects, in both T-cell deficient athymic RNU nude rats and immunocompetent Sprague Dawley rats. Bone volume fraction, bone mineral density and tissue mineral density are higher for athymic RNU nude rats 6 weeks post-surgery. Additionally, these animals show a significantly higher number of total cells and cells with non-lymphocyte morphology at the defect site, while the number of cells with lymphocyte-like morphology is lower. Hydrogel degradation is slower and the remaining alginate fragments are surrounded by a thicker fibrous capsule. Ossification islands originating from alginate residues suggest that encapsulated MSCs differentiate into the osteogenic lineage and initiate the mineralization process. However, this effect is insufficient to fully bridge the bone defect in both animal models. Alginate hydrogels can be used to deliver MSCs and thereby recruit endogenous cells through paracrine signaling, but additional osteogenic stimuli are needed to regenerate critical-sized segmental femoral defects.

PMID:
32046626
DOI:
10.1089/ten.TEA.2019.0310

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