Prevascularized hydrogels with mature vascular networks promote the regeneration of critical-size calvarial bone defects in vivo
Ramesh Subbiah
Division of Biomaterials and Biomechanics, Department of Restorative Dentistry, School of Dentistry, Oregon Health and Science University, Portland, Oregon, USA
Search for more papers by this authorGreeshma Thrivikraman
Division of Biomaterials and Biomechanics, Department of Restorative Dentistry, School of Dentistry, Oregon Health and Science University, Portland, Oregon, USA
Search for more papers by this authorS. Prakash Parthiban
Division of Biomaterials and Biomechanics, Department of Restorative Dentistry, School of Dentistry, Oregon Health and Science University, Portland, Oregon, USA
Search for more papers by this authorJames M. Jones
Center for Regenerative Medicine, Oregon Health and Science University, Portland, Oregon, USA
Search for more papers by this authorAvathamsa Athirasala
Department of Biomedical Engineering, Oregon Health and Science University, Portland, Oregon, USA
Search for more papers by this authorHua Xie
Center for Regenerative Medicine, Oregon Health and Science University, Portland, Oregon, USA
Search for more papers by this authorCorresponding Author
Luiz E. Bertassoni
Division of Biomaterials and Biomechanics, Department of Restorative Dentistry, School of Dentistry, Oregon Health and Science University, Portland, Oregon, USA
Center for Regenerative Medicine, Oregon Health and Science University, Portland, Oregon, USA
Department of Biomedical Engineering, Oregon Health and Science University, Portland, Oregon, USA
Cancer Early Detection Advanced Research (CEDAR) Center, Knight Cancer Institute, Oregon Health and Science University, Portland, Oregon, USA
Correspondence
Luiz E. Bertassoni, Division of Biomaterials and Biomechanics, Department of Restorative Dentistry, School of Dentistry, Oregon Health and Science University, Portland, Oregon, USA.
Email: [email protected]
Search for more papers by this authorRamesh Subbiah
Division of Biomaterials and Biomechanics, Department of Restorative Dentistry, School of Dentistry, Oregon Health and Science University, Portland, Oregon, USA
Search for more papers by this authorGreeshma Thrivikraman
Division of Biomaterials and Biomechanics, Department of Restorative Dentistry, School of Dentistry, Oregon Health and Science University, Portland, Oregon, USA
Search for more papers by this authorS. Prakash Parthiban
Division of Biomaterials and Biomechanics, Department of Restorative Dentistry, School of Dentistry, Oregon Health and Science University, Portland, Oregon, USA
Search for more papers by this authorJames M. Jones
Center for Regenerative Medicine, Oregon Health and Science University, Portland, Oregon, USA
Search for more papers by this authorAvathamsa Athirasala
Department of Biomedical Engineering, Oregon Health and Science University, Portland, Oregon, USA
Search for more papers by this authorHua Xie
Center for Regenerative Medicine, Oregon Health and Science University, Portland, Oregon, USA
Search for more papers by this authorCorresponding Author
Luiz E. Bertassoni
Division of Biomaterials and Biomechanics, Department of Restorative Dentistry, School of Dentistry, Oregon Health and Science University, Portland, Oregon, USA
Center for Regenerative Medicine, Oregon Health and Science University, Portland, Oregon, USA
Department of Biomedical Engineering, Oregon Health and Science University, Portland, Oregon, USA
Cancer Early Detection Advanced Research (CEDAR) Center, Knight Cancer Institute, Oregon Health and Science University, Portland, Oregon, USA
Correspondence
Luiz E. Bertassoni, Division of Biomaterials and Biomechanics, Department of Restorative Dentistry, School of Dentistry, Oregon Health and Science University, Portland, Oregon, USA.
Email: [email protected]
Search for more papers by this authorRamesh Subbiah, Greeshma Thrivikraman, and S. Prakash Parthiban contributed equally to this study.
Abstract
Adequate vascularization of scaffolds is a prerequisite for successful repair and regeneration of lost and damaged tissues. It has been suggested that the maturity of engineered vascular capillaries, which is largely determined by the presence of functional perivascular mural cells (or pericytes), plays a vital role in maintaining vessel integrity during tissue repair and regeneration. Here, we investigated the role of pericyte-supported-engineered capillaries in regenerating bone in a critical-size rat calvarial defect model. Prior to implantation, human umbilical vein endothelial cells and human bone marrow stromal cells (hBMSCs) were cocultured in a collagen hydrogel to induce endothelial cell morphogenesis into microcapillaries and hBMSC differentiation into pericytes. Upon implantation into the calvarial bone defects (8 mm), the prevascularized hydrogels showed better bone formation than either untreated controls or defects treated with autologous bone grafts (positive control). Bone formation parameters such as bone volume, coverage area, and vascularity were significantly better in the prevascularized hydrogel group than in the autologous bone group. Our results demonstrate that tissue constructs engineered with pericyte-supported vascular capillaries may approximate the regenerative capacity of autologous bone, despite the absence of osteoinductive or vasculogenic growth factors.
CONFLICT OF INTERESTS
The authors declare no potential conflicts of interest with respect to the authorship and/or publication of this article.
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