title: Synthesis and physicochemical, in vitro and in vivo evaluation of an anisotropic, nanocrystalline hydroxyapatite bisque scaffold with parallel-aligned pores mimicking the microstructure of cortical bone.
abstract: Scaffolds for bone regeneration are mostly prepared with an isotropic, sponge-like structure mimicking the architecture of trabecular bone. We have developed an anisotropic bioceramic with parallel aligned pores resembling the honeycomb arrangement of Haversian canals of cortical bone and investigated its potential as a scaffold for tissue engineering. Parallel channel-like pores were generated by ionotropic gelation of an alginate-hydroxyapatite (HA) slurry, followed by ceramic processing. Organic components were thermally removed at 650 °C, whereas the pore system was preserved in the obtained HA bioceramic in the processing stage of a bisque. Even without further sintering at higher temperatures, the anisotropic HA bisque (AHAB) became mechanically stable with a compressive strength (4.3 MPa) comparable to that of native trabecular bone. Owing to the low-temperature treatment, a nanocrystalline microstructure with high porosity (82%) and surface area (24.9 m(2)/g) was achieved that kept the material dissolvable in acidic conditions, similar to osteoclastic degradation of bone. Human mesenchymal stem cells (hMSCs) adhered, proliferated and differentiated into osteoblasts when osteogenically induced, indicating the cytocompatibility of the bisque scaffold. Furthermore, we demonstrated fusion of human monocytes to osteoclast-like cells in vitro on this substrate, similar to the natural pathway. Biocompatibility was demonstrated in vivo by implantation of the bisque ceramic into cortical rabbit femur defects, followed by histological analysis, where new bone formation inside the channel-like pores and generation of an osteon-like tissue morphology was observed.
authors.affiliation: Technische Universität Dresden, Medical Faculty and University Hospital, Centre for Translational Bone, Joint and Soft Tissue Research, Dresden, Germany.|Technische Universität Dresden, Institute for Materials Science, Max Bergmann Centre of Biomaterials, Dresden, Germany.
authors.forename: F
authors.initials: F
authors.lastname: Despang
authors.affiliation: Technische Universität Dresden, Medical Faculty and University Hospital, Centre for Translational Bone, Joint and Soft Tissue Research, Dresden, Germany.|Technische Universität Dresden, Institute for Materials Science, Max Bergmann Centre of Biomaterials, Dresden, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Bernhardt
authors.affiliation: Technische Universität Dresden, Medical Faculty and University Hospital, Centre for Translational Bone, Joint and Soft Tissue Research, Dresden, Germany.|Technische Universität Dresden, Institute for Materials Science, Max Bergmann Centre of Biomaterials, Dresden, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Lode
authors.affiliation: TU Bergakademie Freiberg, Institute of Electronic und Sensor Materials, Freiberg, Germany.
authors.forename: R
authors.initials: R
authors.lastname: Dittrich
authors.affiliation: Technische Universität Dresden, Institute for Materials Science, Max Bergmann Centre of Biomaterials, Dresden, Germany.
authors.forename: T
authors.initials: T
authors.lastname: Hanke
authors.affiliation: Sree Chitra Tirunal Institute for Medical Sciences and Technology, Thiruvananthapuram, Kerala, India.
authors.forename: S J
authors.initials: SJ
authors.lastname: Shenoy
authors.affiliation: Sree Chitra Tirunal Institute for Medical Sciences and Technology, Thiruvananthapuram, Kerala, India.
authors.forename: S
authors.initials: S
authors.lastname: Mani
authors.affiliation: Sree Chitra Tirunal Institute for Medical Sciences and Technology, Thiruvananthapuram, Kerala, India.
authors.forename: A
authors.initials: A
authors.lastname: John
authors.affiliation: Technische Universität Dresden, Medical Faculty and University Hospital, Centre for Translational Bone, Joint and Soft Tissue Research, Dresden, Germany.|Technische Universität Dresden, Institute for Materials Science, Max Bergmann Centre of Biomaterials, Dresden, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Gelinsky
mesh_terms: D000818:Animals; D016880:Anisotropy; D018786:Bone Substitutes / Q000737:chemistry / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects; D017886:Durapatite / Q000737:chemistry / Q000494:pharmacology; D005260:Female; D005269:Femur / Q000737:chemistry / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D008297:Male; D059630:Mesenchymal Stem Cells / Q000378:metabolism / Q000473:pathology; D053758:Nanoparticles / Q000737:chemistry*; D010006:Osteoblasts / Q000378:metabolism / Q000473:pathology; D010012:Osteogenesis / Q000187:drug effects; D016062:Porosity; D011817:Rabbits; D054457:Tissue Scaffolds / Q000737:chemistry*
chemical_list: D018786:Bone Substitutes; D017886:Durapatite
keywords: anisotropic scaffold; biomimetic material; bone tissue engineering; cytocompatibility; femoral defect; human mesenchymal stem cells; ionotropic gelation of alginate; nanocrystalline apatite