title: Surface-enrichment with hydroxyapatite nanoparticles in stereolithography-fabricated composite polymer scaffolds promotes bone repair.
abstract: Fabrication of composite scaffolds using stereolithography (SLA) for bone tissue engineering has shown great promises. However, in order to trigger effective bone formation and implant integration, exogenous growth factors are commonly combined to scaffold materials. In this study, we fabricated biodegradable composite scaffolds using SLA and endowed them with osteopromotive properties in the absence of biologics. First we prepared photo-crosslinkable poly(trimethylene carbonate) (PTMC) resins containing 20 and 40wt% of hydroxyapatite (HA) nanoparticles and fabricated scaffolds with controlled macro-architecture. Then, we conducted experiments to investigate how the incorporation of HA in photo-crosslinked PTMC matrices improved human bone marrow stem cells osteogenic differentiation in vitro and kinetic of bone healing in vivo. We observed that bone regeneration was significantly improved using composite scaffolds containing as low as 20wt% of HA, along with difference in terms of osteogenesis and degree of implant osseointegration. Further investigations revealed that SLA process was responsible for the formation of a rich microscale layer of HA corralling scaffolds. To summarize, this work is of substantial importance as it shows how the fabrication of hierarchical biomaterials via surface-enrichment of functional HA nanoparticles in composite polymer stereolithographic structures could impact in vitro and in vivo osteogenesis.
  
  
  
  This study reports for the first time the enhance osteopromotion of composite biomaterials, with controlled macro-architecture and microscale distribution of hydroxyapatite particles, manufactured by stereolithography. In this process, the hydroxyapatite particles are not only embedded into an erodible polymer matrix, as reported so far in the literature, but concentrated at the surface of the structures. This leads to robust in vivo bone formation at low concentration of hydroxyapatite. The reported 3D self-corralling composite architecture provides significant opportunities to develop functional biomaterials for bone repair and tissue engineering.
authors.affiliation: AO Research Institute Davos, Clavadelerstrasse 8, CH 7270 Davos, Switzerland.
authors.forename: O
authors.initials: O
authors.lastname: Guillaume
authors.affiliation: MIRA Institute for Biomedical Engineering and Technical Medicine, Department of Biomaterials Science and Technology, University of Twente, P.O. Box 217, 7500 AE Enschede, The Netherlands.
authors.forename: M A
authors.initials: MA
authors.lastname: Geven
authors.affiliation: AO Research Institute Davos, Clavadelerstrasse 8, CH 7270 Davos, Switzerland.
authors.forename: C M
authors.initials: CM
authors.lastname: Sprecher
authors.affiliation: AO Research Institute Davos, Clavadelerstrasse 8, CH 7270 Davos, Switzerland.
authors.forename: V A
authors.initials: VA
authors.lastname: Stadelmann
authors.affiliation: MIRA Institute for Biomedical Engineering and Technical Medicine, Department of Biomaterials Science and Technology, University of Twente, P.O. Box 217, 7500 AE Enschede, The Netherlands.
authors.forename: D W
authors.initials: DW
authors.lastname: Grijpma
authors.affiliation: Shanghai Key Laboratory of Orthopedic Implants, Department of Orthopedic Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: T T
authors.initials: TT
authors.lastname: Tang
authors.affiliation: Translational Medicine Research and Development Centre, Institute of Biomedical and Health Engineering, Shenzhen Institute of Advanced Technology, The Chinese Academy of Sciences, Shenzhen, China.
authors.forename: L
authors.initials: L
authors.lastname: Qin
authors.affiliation: Translational Medicine Research and Development Centre, Institute of Biomedical and Health Engineering, Shenzhen Institute of Advanced Technology, The Chinese Academy of Sciences, Shenzhen, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Lai
authors.affiliation: AO Research Institute Davos, Clavadelerstrasse 8, CH 7270 Davos, Switzerland.
authors.forename: M
authors.initials: M
authors.lastname: Alini
authors.affiliation: Xpand Biotechnology BV, Professor Bronkhorstlaan 10-d, 3723 MB Bilthoven, The Netherlands.
authors.forename: J D
authors.initials: JD
authors.lastname: de Bruijn
authors.affiliation: Xpand Biotechnology BV, Professor Bronkhorstlaan 10-d, 3723 MB Bilthoven, The Netherlands.
authors.forename: H
authors.initials: H
authors.lastname: Yuan
authors.affiliation: AO Research Institute Davos, Clavadelerstrasse 8, CH 7270 Davos, Switzerland.
authors.forename: R G
authors.initials: RG
authors.lastname: Richards
authors.affiliation: AO Research Institute Davos, Clavadelerstrasse 8, CH 7270 Davos, Switzerland. Electronic address: david.eglin@aofoundation.org.
authors.forename: D
authors.initials: D
authors.lastname: Eglin
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000378:metabolism / Q000473:pathology*; D001861:Bone Regeneration / Q000187:drug effects*; D017886:Durapatite / Q000737:chemistry / Q000494:pharmacology; D005260:Female; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000378:metabolism* / Q000473:pathology; D053758:Nanoparticles / Q000737:chemistry*; D010012:Osteogenesis / Q000187:drug effects*; D011817:Rabbits; D012886:Skull / Q000293:injuries / Q000378:metabolism / Q000473:pathology; D054457:Tissue Scaffolds / Q000737:chemistry*
chemical_list: D017886:Durapatite
keywords: Bone regeneration; Hydroxyapatite nanoparticles; Osteoconductive scaffold; Poly(trimethylene carbonate); Stereolithography; Surface-enrichment