title: Enhancing the biological performance of synthetic polymeric materials by decoration with engineered, decellularized extracellular matrix.
abstract: Materials based on synthetic polymers can be extensively tailored in their physical properties but often suffer from limited biological functionality. Here we tested the hypothesis that the biological performance of 3D synthetic polymer-based scaffolds can be enhanced by extracellular matrix (ECM) deposited by cells in vitro and subsequently decellularized. The hypothesis was tested in the context of bone graft substitutes, using polyesterurethane (PEU) foams and mineralized ECM laid by human mesenchymal stromal cells (hMSC). A perfusion-based bioreactor system was critically employed to uniformly seed and culture hMSC in the scaffolds and to efficiently decellularize (94% DNA reduction) the resulting ECM while preserving its main organic and inorganic components. As compared to plain PEU, the decellularized ECM-polymer hybrids supported the osteoblastic differentiation of newly seeded hMSC by up-regulating the mRNA expression of typical osteoblastic genes (6-fold higher bone sialoprotein; 4-fold higher osteocalcin and osteopontin) and increasing calcium deposition (6-fold higher), approaching the performance of ceramic-based materials. After ectopic implantation in nude mice, the decellularized hybrids induced the formation of a mineralized matrix positively immunostained for bone sialoprotein and resembling an immature osteoid tissue. Our findings consolidate the perspective of bioreactor-based production of ECM-decorated polymeric scaffolds as off-the-shelf materials combining tunable physical properties with the physiological presentation of instructive biological signals.
authors.affiliation: Department of Surgery, University Hospital Basel, Hebelstrasse 20, CH-4031 Basel, Switzerland.
authors.forename: Nasser
authors.initials: N
authors.lastname: Sadr
authors.forename: Benjamin E
authors.initials: BE
authors.lastname: Pippenger
authors.forename: Arnaud
authors.initials: A
authors.lastname: Scherberich
authors.forename: David
authors.initials: D
authors.lastname: Wendt
authors.forename: Sara
authors.initials: S
authors.lastname: Mantero
authors.forename: Ivan
authors.initials: I
authors.lastname: Martin
authors.forename: Adam
authors.initials: A
authors.lastname: Papadimitropoulos
mesh_terms: D000818:Animals; D001672:Biocompatible Materials; D002454:Cell Differentiation; D005109:Extracellular Matrix; D005434:Flow Cytometry; D020869:Gene Expression Profiling; D006801:Humans; D007150:Immunohistochemistry; D059630:Mesenchymal Stem Cells / Q000166:cytology; D051379:Mice; D008819:Mice, Nude; D010006:Osteoblasts / Q000166:cytology; D011108:Polymers; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D023822:Tissue Engineering
chemical_list: D001672:Biocompatible Materials; D011108:Polymers