Mineral deposition and vascular invasion of hydroxyapatite reinforced collagen scaffolds seeded with human adipose-derived stem cells

Abstract Background Collagen-based scaffolds reinforced with hydroxyapatite (HA) are an attractive choice for bone tissue engineering because their composition mimics that of bone. We previously reported the development of compression-molded collagen-HA scaffolds that exhibited high porosity, interc...

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Main Authors: Holly E. Weiss-Bilka, Matthew J. Meagher, Joshua A. Gargac, Glen L. Niebur, Ryan K. Roeder, Diane R. Wagner
Format: Article
Language:English
Published: American Association for the Advancement of Science (AAAS) 2019-10-01
Series:Biomaterials Research
Subjects:
Online Access:http://link.springer.com/article/10.1186/s40824-019-0167-9
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author Holly E. Weiss-Bilka
Matthew J. Meagher
Joshua A. Gargac
Glen L. Niebur
Ryan K. Roeder
Diane R. Wagner
author_facet Holly E. Weiss-Bilka
Matthew J. Meagher
Joshua A. Gargac
Glen L. Niebur
Ryan K. Roeder
Diane R. Wagner
author_sort Holly E. Weiss-Bilka
collection DOAJ
description Abstract Background Collagen-based scaffolds reinforced with hydroxyapatite (HA) are an attractive choice for bone tissue engineering because their composition mimics that of bone. We previously reported the development of compression-molded collagen-HA scaffolds that exhibited high porosity, interconnected pores, and mechanical properties that were well-suited for surgical handling and fixation. The objective of this study was to investigate these novel collagen-HA scaffolds in combination with human adipose-derived stem cells (hASCs) as a template for bone formation in a subcutaneous athymic mouse model. Methods Collagen-HA scaffolds and collagen-only scaffolds were fabricated as previously described, and a clinically approved bone void filler was used as a control for the material. Constructs were seeded with hASCs and were pre-treated with either control or osteogenic media. A cell-free group was also included. Scaffolds were implanted subcutaneously in the backs of athymic nude mice for 8 weeks. Mineral deposition was quantified via micro-computed tomography. Histological and immunofluorescence images of the explants were used to analyze their vascular invasion, remodeling and cellularity. Results Cell-free collagen-HA scaffolds and those that were pre-seeded with osteogenically differentiated hASCs supported mineral deposition and vascular invasion at comparable rates, while cell-seeded constructs treated with the control medium showed lower mineralization after implantation. HA-reinforcement allowed collagen constructs to maintain their shape, provided improved cell-tissue-scaffold integration, and resulted in a more organized tissue when pre-treated in an osteogenic medium. Scaffold type and pre-treatment also determined osteoclast activity and therefore potential remodeling of the constructs. Conclusions The results of this study cumulatively indicate that treatment medium and scaffold composition direct mineralization and angiogenic tissue formation in an ectopic model. The data suggest that it may be necessary to match the scaffold with a particular cell type and cell-specific pre-treatment to achieve optimal bone formation.
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spelling doaj.art-1afda1b17fcf48a489d859a621bbe9072024-03-02T15:03:50ZengAmerican Association for the Advancement of Science (AAAS)Biomaterials Research2055-71242019-10-0123111310.1186/s40824-019-0167-9Mineral deposition and vascular invasion of hydroxyapatite reinforced collagen scaffolds seeded with human adipose-derived stem cellsHolly E. Weiss-Bilka0Matthew J. Meagher1Joshua A. Gargac2Glen L. Niebur3Ryan K. Roeder4Diane R. Wagner5Bioengineering Graduate Program, University of Notre DameBioengineering Graduate Program, University of Notre DameSchool of Engineering, University of Mount UnionBioengineering Graduate Program, University of Notre DameBioengineering Graduate Program, University of Notre DameDepartment of Mechanical and Energy Engineering, Indiana University-Purdue University IndianapolisAbstract Background Collagen-based scaffolds reinforced with hydroxyapatite (HA) are an attractive choice for bone tissue engineering because their composition mimics that of bone. We previously reported the development of compression-molded collagen-HA scaffolds that exhibited high porosity, interconnected pores, and mechanical properties that were well-suited for surgical handling and fixation. The objective of this study was to investigate these novel collagen-HA scaffolds in combination with human adipose-derived stem cells (hASCs) as a template for bone formation in a subcutaneous athymic mouse model. Methods Collagen-HA scaffolds and collagen-only scaffolds were fabricated as previously described, and a clinically approved bone void filler was used as a control for the material. Constructs were seeded with hASCs and were pre-treated with either control or osteogenic media. A cell-free group was also included. Scaffolds were implanted subcutaneously in the backs of athymic nude mice for 8 weeks. Mineral deposition was quantified via micro-computed tomography. Histological and immunofluorescence images of the explants were used to analyze their vascular invasion, remodeling and cellularity. Results Cell-free collagen-HA scaffolds and those that were pre-seeded with osteogenically differentiated hASCs supported mineral deposition and vascular invasion at comparable rates, while cell-seeded constructs treated with the control medium showed lower mineralization after implantation. HA-reinforcement allowed collagen constructs to maintain their shape, provided improved cell-tissue-scaffold integration, and resulted in a more organized tissue when pre-treated in an osteogenic medium. Scaffold type and pre-treatment also determined osteoclast activity and therefore potential remodeling of the constructs. Conclusions The results of this study cumulatively indicate that treatment medium and scaffold composition direct mineralization and angiogenic tissue formation in an ectopic model. The data suggest that it may be necessary to match the scaffold with a particular cell type and cell-specific pre-treatment to achieve optimal bone formation.http://link.springer.com/article/10.1186/s40824-019-0167-9BoneOsteogenesisAngiogenesisAdipose-derived stem cellCollagenHydroxyapatite
spellingShingle Holly E. Weiss-Bilka
Matthew J. Meagher
Joshua A. Gargac
Glen L. Niebur
Ryan K. Roeder
Diane R. Wagner
Mineral deposition and vascular invasion of hydroxyapatite reinforced collagen scaffolds seeded with human adipose-derived stem cells
Biomaterials Research
Bone
Osteogenesis
Angiogenesis
Adipose-derived stem cell
Collagen
Hydroxyapatite
title Mineral deposition and vascular invasion of hydroxyapatite reinforced collagen scaffolds seeded with human adipose-derived stem cells
title_full Mineral deposition and vascular invasion of hydroxyapatite reinforced collagen scaffolds seeded with human adipose-derived stem cells
title_fullStr Mineral deposition and vascular invasion of hydroxyapatite reinforced collagen scaffolds seeded with human adipose-derived stem cells
title_full_unstemmed Mineral deposition and vascular invasion of hydroxyapatite reinforced collagen scaffolds seeded with human adipose-derived stem cells
title_short Mineral deposition and vascular invasion of hydroxyapatite reinforced collagen scaffolds seeded with human adipose-derived stem cells
title_sort mineral deposition and vascular invasion of hydroxyapatite reinforced collagen scaffolds seeded with human adipose derived stem cells
topic Bone
Osteogenesis
Angiogenesis
Adipose-derived stem cell
Collagen
Hydroxyapatite
url http://link.springer.com/article/10.1186/s40824-019-0167-9
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