title: Modulation of Host Osseointegration during Bone Regeneration by Controlling Exogenous Stem Cells Differentiation Using a Material Approach.
abstract: Stem cell-based tissue engineering for large bone defect healing has attracted enormous attention in regenerative medicine. However, sufficient osseointegration of the grafts combined with exogenous stem cells still remains a major challenge. Here we developed a material approach to modulate the integration of the grafts to the host tissue when exogenous bone marrow stromal cells (BMSCs) were used as donor cells. Distinctive osseointegration of bone grafts was observed as we varied the content of hydroxyapatite (HA) in the tissue scaffolds implanted in a mouse femur model. More than 80% of new bone was formed in the first two weeks of implantation in high HA content scaffold but lack of host integration while only less than 5% of the new bone was formed during this time period in the no HA group but with much stronger host integration. Cell origin analysis leveraging GFP reporter indicates new bone in HA containing groups was mainly derived from donor BMSCs. In comparison, both host and donor cells were found on new bone surface in the no HA groups which led to seamless bridging between host tissue and the scaffold. Most importantly, host integration during bone formation is closely dictated to the content of HA present in the scaffolds. Taken together, we demonstrate a material approach to modulate the osseointegration of bone grafts in the context of exogenous stem cell-based bone healing strategy which might lead to fully functional bone tissue regeneration.
authors.affiliation: Department of Materials Science and Engineering, Department of Reconstructive Sciences, School of Dental Medicine, University of Connecticut Health Center, Farmington, CT 06030, USA, University of Connecticut, Storrs, CT 06269, USA.
authors.forename: Xiaohua
authors.initials: X
authors.lastname: Yu
authors.affiliation: Department of Materials Science and Engineering, Department of Reconstructive Sciences, School of Dental Medicine, University of Connecticut Health Center, Farmington, CT 06030, USA, University of Connecticut, Storrs, CT 06269, USA.
authors.forename: Liping
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Materials Science and Engineering, Department of Reconstructive Sciences, School of Dental Medicine, University of Connecticut Health Center, Farmington, CT 06030, USA, University of Connecticut, Storrs, CT 06269, USA.
authors.forename: Zengmin
authors.initials: Z
authors.lastname: Xia
authors.affiliation: Department of Materials Science and Engineering, Department of Reconstructive Sciences, School of Dental Medicine, University of Connecticut Health Center, Farmington, CT 06030, USA, University of Connecticut, Storrs, CT 06269, USA.
authors.forename: Li
authors.initials: L
authors.lastname: Chen
authors.affiliation: Department of Materials Science and Engineering, Department of Reconstructive Sciences, School of Dental Medicine, University of Connecticut Health Center, Farmington, CT 06030, USA, University of Connecticut, Storrs, CT 06269, USA.
authors.forename: Xi
authors.initials: X
authors.lastname: Jiang
authors.affiliation: Department of Materials Science and Engineering, Department of Reconstructive Sciences, School of Dental Medicine, University of Connecticut Health Center, Farmington, CT 06030, USA, University of Connecticut, Storrs, CT 06269, USA.
authors.forename: David
authors.initials: D
authors.lastname: Rowe
authors.affiliation: Department of Materials Science and Engineering, Department of Reconstructive Sciences, School of Dental Medicine, University of Connecticut Health Center, Farmington, CT 06030, USA, University of Connecticut, Storrs, CT 06269, USA.
authors.forename: Mei
authors.initials: M
authors.lastname: Wei