title: Effect of collagen-glycosaminoglycan scaffold pore size on matrix mineralization and cellular behavior in different cell types.
abstract: We have previously examined osteoblast behavior on porous collagen-glycosaminoglycan (CG) scaffolds with a range of mean pore sizes demonstrating superior cell attachment and migration in scaffolds with the largest pores (325 μm). Scaffolds provide a framework for construct development; therefore, it is crucial to identify the optimal pore size for augmented tissue formation. Utilizing the same range of scaffolds (85 μm - 325 μm), this study aimed to examine the effects of mean pore size on subsequent osteoblast differentiation and matrix mineralization, and to understand the mechanism by which pore size influences behavior of different cell types. Consequently, primary mesenchymal stem cells (MSCs) were assessed and their behavior compared to osteoblasts. Results demonstrated that scaffolds with the largest pore size (325 μm) facilitated improved osteoblast infiltration, earlier expression of mature bone markers osteopontin (OPN) and osteocalcin (OCN), and increased mineralization. MSCs responded similarly to osteoblasts whereby cell attachment and scaffold infiltration improved with increasing pore size. However, MSCs showed reduced cell motility, proliferation, and scaffold infiltration compared to osteoblasts. This was associated with differences in the profile of integrin subunits (α2) and collagen receptors (CD44), indicating that osteoblasts have a stronger affinity for CG scaffolds compared to MSCs. In summary, these results reveal how larger pores promote improved cell infiltration, essential for construct development, however the optimal scaffold pore size can be cell type specific. As such, this study highlights a necessity to tailor both scaffold micro-architecture and cell-type when designing constructs for successful bone tissue engineering applications.
authors.affiliation: School of Medicine & Medical Science, University College Dublin, Dublin, Ireland.|Tissue Engineering Research Group, Department of Anatomy, Royal College of Surgeons in Ireland (RCSI), Dublin, Ireland.|Trinity Centre for Bioengineering, Trinity College Dublin (TCD), Dublin, Ireland.
authors.forename: Ciara M
authors.initials: CM
authors.lastname: Murphy
authors.affiliation: Tissue Engineering Research Group, Department of Anatomy, Royal College of Surgeons in Ireland (RCSI), Dublin, Ireland.|Trinity Centre for Bioengineering, Trinity College Dublin (TCD), Dublin, Ireland.|Advanced Materials and Bioengineering Research Centre (AMBER) RCSI & TCD, Dublin, Ireland.
authors.forename: Garry P
authors.initials: GP
authors.lastname: Duffy
authors.affiliation: Orthopaedic Research & Biotechnology Unit the Children's Hospital at Westmead.|Discipline of Paediatrics and Child Health, University of Sydney, Sydney, Australia.
authors.forename: Aaron
authors.initials: A
authors.lastname: Schindeler
authors.affiliation: Tissue Engineering Research Group, Department of Anatomy, Royal College of Surgeons in Ireland (RCSI), Dublin, Ireland.|Trinity Centre for Bioengineering, Trinity College Dublin (TCD), Dublin, Ireland.|Advanced Materials and Bioengineering Research Centre (AMBER) RCSI & TCD, Dublin, Ireland.
authors.forename: Fergal J
authors.initials: FJ
authors.lastname: O'brien
mesh_terms: D000818:Animals; D002113:Calcification, Physiologic / Q000187:drug effects*; D002417:Cattle; D002448:Cell Adhesion / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects; D048430:Cell Shape / Q000187:drug effects; D003094:Collagen / Q000494:pharmacology*; D005109:Extracellular Matrix / Q000378:metabolism*; D005434:Flow Cytometry; D006025:Glycosaminoglycans / Q000494:pharmacology*; D016023:Integrins / Q000378:metabolism; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000187:drug effects; D051379:Mice; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects; D010012:Osteogenesis / Q000187:drug effects; D053495:Osteopontin / Q000378:metabolism; D016062:Porosity; D017208:Rats, Wistar; D012754:Sharks; D054457:Tissue Scaffolds / Q000737:chemistry*
chemical_list: D006025:Glycosaminoglycans; D016023:Integrins; D053495:Osteopontin; D003094:Collagen
keywords: bone tissue engineering; cell infiltration; mesenchymal stem cell; pore size; scaffold