title: In vitro and in vivo bone formation potential of surface calcium phosphate-coated polycaprolactone and polycaprolactone/bioactive glass composite scaffolds.
abstract: In this study, polycaprolactone (PCL)-based composite scaffolds containing 50wt% of 45S5 Bioglass(®) (45S5) or strontium-substituted bioactive glass (SrBG) particles were fabricated into scaffolds using an additive manufacturing technique for bone tissue engineering purposes. The PCL scaffolds were surface coated with calcium phosphate (CaP) to enable further comparison of the osteoinductive potential of different scaffolds: PCL (control), PCL/CaP-coated, PCL/50-45S5 and PCL/50-SrBG scaffolds. The PCL/50-45S5 and PCL/50-SrBG composite scaffolds were reproducibly manufactured with a morphology highly resembling that of PCL only scaffolds. However, 50wt% loading of the bioactive glass (BG) particles into the PCL bulk decreased the scaffold's compressive Young's modulus. Coating of PCL scaffolds with CaP had a negligible effect on the scaffold's porosity and compressive Young's modulus. When immersed in culture media, BG dissolution ions (Si and Sr) were detected for up to 10weeks in the immersion media and surface precipitates were formed on both PCL/50-45S5 and PCL/50-SrBG scaffolds' surfaces, indicating good in vitro bioactivity. In vitro cell studies were conducted using sheep bone marrow stromal cells (BMSCs) under non-osteogenic or osteogenic conditioned media, and under static or dynamic culture environments. All scaffolds were able to support cell adhesion, growth and proliferation. However, when cultured in non-osteogenic media, only PCL/CaP, PCL/50-45S5 and PCL/50-SrBG scaffolds showed an up-regulation of osteogenic gene expression. Additionally, under a dynamic culture environment, the rate of cell growth, proliferation and osteoblast-related gene expression was enhanced across all scaffold groups. Subsequently, PCL/CaP, PCL/50-45S5 and PCL/50-SrBG scaffolds, with or without seeded cells, were implanted subcutaneously into nude rats for the evaluation of osteoinductivity potential. After 8 and 16weeks, host tissue infiltrated well into the scaffolds, but no mature bone formation was observed in any scaffolds groups.
  
  
  CONCLUSIONS
  This novelty of this research work is that it provide a comprehensive comparison, both in vitro and in vivo, between 3 different composite materials widely used in the field of bone tissue engineering for their bone regeneration capabilities. The materials used in this study include polycaprolactone, 45S5 Bioglass, strontium-substituted bioactive glass and calcium phosphate. Additionally, the composite materials were fabricated into the form of 3D scaffolds using additive manufacturing technique, a widely used technique in tissue engineering.
authors.affiliation: Institute of Health and Biomedical Innovation, Queensland University of Technology, 60 Musk Avenue, Kelvin Grove, 4059 Brisbane, Australia; Department of Experimental Trauma Surgery, Klinikum Rechts der Isar, Technical University Munich, Ismaninger 22, 81675 Munich, Germany.
authors.forename: Patrina S P
authors.initials: PSP
authors.lastname: Poh
authors.affiliation: Institute of Health and Biomedical Innovation, Queensland University of Technology, 60 Musk Avenue, Kelvin Grove, 4059 Brisbane, Australia; Institute for Advanced Study, Technical University Munich, Lichtenbergstrasse 2a, 85748 Garching, Munich, Germany.
authors.forename: Dietmar W
authors.initials: DW
authors.lastname: Hutmacher
authors.affiliation: Institute of Health and Biomedical Innovation, Queensland University of Technology, 60 Musk Avenue, Kelvin Grove, 4059 Brisbane, Australia; Department of Orthopaedic Surgery, Koenig-Ludwig Haus, University of Wuerzburg, Brettreichstr. 11, 97074 Wuerzburg, Germany.
authors.forename: Boris M
authors.initials: BM
authors.lastname: Holzapfel
authors.affiliation: Department of Materials and Department of Bioengineering, Institute of Biomedical Engineering, Imperial College London, Exhibition Road, London SW7 2AZ, United Kingdom.
authors.forename: Anu K
authors.initials: AK
authors.lastname: Solanki
authors.affiliation: Department of Materials and Department of Bioengineering, Institute of Biomedical Engineering, Imperial College London, Exhibition Road, London SW7 2AZ, United Kingdom.
authors.forename: Molly M
authors.initials: MM
authors.lastname: Stevens
authors.affiliation: Institute of Health and Biomedical Innovation, Queensland University of Technology, 60 Musk Avenue, Kelvin Grove, 4059 Brisbane, Australia. Electronic address: mia.woodruff@qut.edu.au.
authors.forename: Maria A
authors.initials: MA
authors.lastname: Woodruff
mesh_terms: D000818:Animals; D002130:Calcium Phosphates / Q000737:chemistry / Q000494:pharmacology; D002516:Ceramics / Q000737:chemistry / Q000494:pharmacology; D020099:Coated Materials, Biocompatible / Q000737:chemistry / Q000494:pharmacology; D010012:Osteogenesis / Q000187:drug effects*; D011091:Polyesters / Q000737:chemistry / Q000494:pharmacology; D051381:Rats; D011923:Rats, Nude; D012756:Sheep; D013499:Surface Properties; D054457:Tissue Scaffolds / Q000737:chemistry*
chemical_list: C022107:Bioglass; D002130:Calcium Phosphates; D020099:Coated Materials, Biocompatible; D011091:Polyesters; C016240:polycaprolactone; C020243:calcium phosphate
keywords: 45S5 Bioglass; Bioactive glass; Bone tissue engineering; Polycaprolactone; Strontium