Three dimensional printing of calcium sulfate and mesoporous bioactive glass scaffolds for improving bone regeneration in vitro and in vivo

In the clinic, bone defects resulting from infections, trauma, surgical resection and genetic malformations remain a significant challenge. In the field of bone tissue engineering, three-dimensional (3D) scaffolds are promising for the treatment of bone defects. In this study, calcium sulfate hydrate (CSH)/mesoporous bioactive glass (MBG) scaffolds were successfully fabricated using a 3D printing technique, which had a regular and uniform square macroporous structure, high porosity and excellent apatite mineralization ability. Human bone marrow-derived mesenchymal stem cells (hBMSCs) were cultured on scaffolds to evaluate hBMSC attachment, proliferation and osteogenesis-related gene expression. Critical-sized rat calvarial defects were applied to investigate the effect of CSH/MBG scaffolds on bone regeneration in vivo. The in vitro results showed that CSH/MBG scaffolds stimulated the adhesion, proliferation, alkaline phosphatase (ALP) activity and osteogenesis-related gene expression of hBMSCs. In vivo results showed that CSH/MBG scaffolds could significantly enhance new bone formation in calvarial defects compared to CSH scaffolds. Thus 3D printed CSH/MBG scaffolds would be promising candidates for promoting bone regeneration.

[1]  Su A. Park,et al.  Fabrication of porous polycaprolactone/hydroxyapatite (PCL/HA) blend scaffolds using a 3D plotting system for bone tissue engineering , 2011, Bioprocess and biosystems engineering.

[2]  S. Hollister,et al.  Biomineral Coating Increases Bone Formation by Ex Vivo BMP‐7 Gene Therapy in Rapid Prototyped Poly(l‐lactic acid) (PLLA) and Poly(ε‐caprolactone) (PCL) Porous Scaffolds , 2015, Advanced healthcare materials.

[3]  S. Graves,et al.  Formation of mineralized nodules by bone derived cells in vitro: a model of bone formation? , 1993, American journal of medical genetics.

[4]  Changqing Zhang,et al.  Three dimensionally printed mesoporous bioactive glass and poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) composite scaffolds for bone regeneration. , 2014, Journal of materials chemistry. B.

[5]  X. Cui,et al.  Effects of Chitosan-Coated Pressed Calcium Sulfate Pellet Combined With Recombinant Human Bone Morphogenetic Protein 2 on Restoration of Segmental Bone Defect , 2008, The Journal of craniofacial surgery.

[6]  Qi-yuan Chen,et al.  Effects of surfactants on the microstructure of porous ceramic scaffolds fabricated by foaming for bone tissue engineering , 2009 .

[7]  D. Loca,et al.  The effect of TiO2 nanopowder coating on in vitro bioactivity of porous TiO2 scaffolds , 2015 .

[8]  Shinn-Jyh Ding,et al.  Improvement of in vitro physicochemical properties and osteogenic activity of calcium sulfate cement for bone repair by dicalcium silicate , 2014 .

[9]  Søren Overgaard,et al.  No effect of Osteoset ® , a bone graft substitute, on bone healing in humans: A prospective randomized double-blind study , 2002, Acta orthopaedica Scandinavica.

[10]  Keming Chen,et al.  The preliminary performance study of the 3D printing of a tricalcium phosphate scaffold for the loading of sustained release anti-tuberculosis drugs , 2015, Journal of Materials Science.

[11]  K. Jandt,et al.  Mineralisation of chitosan scaffolds with nano-apatite formation by double diffusion technique. , 2006, Acta biomaterialia.

[12]  Yongxiang Luo,et al.  Hierarchical mesoporous bioactive glass/alginate composite scaffolds fabricated by three-dimensional plotting for bone tissue engineering , 2012, Biofabrication.

[13]  M. Vallet‐Regí,et al.  Interaction of an ordered mesoporous bioactive glass with osteoblasts, fibroblasts and lymphocytes, demonstrating its biocompatibility as a potential bone graft material. , 2010, Acta biomaterialia.

[14]  J. Ricci,et al.  Bone-defect healing with calcium-sulfate particles and cement: an experimental study in rabbit. , 2004, Journal of biomedical materials research. Part B, Applied biomaterials.

[15]  Jianhua Zhang,et al.  3D-printed magnetic Fe3O4/MBG/PCL composite scaffolds with multifunctionality of bone regeneration, local anticancer drug delivery and hyperthermia. , 2014, Journal of materials chemistry. B.

[16]  Richard Appleyard,et al.  The effect of mesoporous bioactive glass on the physiochemical, biological and drug-release properties of poly(DL-lactide-co-glycolide) films. , 2009, Biomaterials.

[17]  Huazi Xu,et al.  Bioactive calcium sulfate/magnesium phosphate cement for bone substitute applications. , 2014, Materials science & engineering. C, Materials for biological applications.

[18]  Yin Xiao,et al.  Structure-property relationships of silk-modified mesoporous bioglass scaffolds. , 2010, Biomaterials.

[19]  Larry L Hench,et al.  Third-Generation Biomedical Materials , 2002, Science.

[20]  Susmita Bose,et al.  Polycaprolactone-Coated 3D Printed Tricalcium Phosphate Scaffolds for Bone Tissue Engineering: In Vitro Alendronate Release Behavior and Local Delivery Effect on In Vivo Osteogenesis , 2014, ACS applied materials & interfaces.

[21]  R. Holmes,et al.  Hydroxyapatite/Calcium Carbonate (HA/CC) vs. Plaster of Paris: A Histomorphometric and Radiographic Study in a Rabbit Tibial Defect Model , 2002, Calcified Tissue International.

[22]  X. Niu,et al.  Exosomes Secreted by Human-Induced Pluripotent Stem Cell-Derived Mesenchymal Stem Cells Repair Critical-Sized Bone Defects through Enhanced Angiogenesis and Osteogenesis in Osteoporotic Rats , 2016, International journal of biological sciences.

[23]  Do-Gyoon Kim,et al.  Preparation and characterization of nano-sized hydroxyapatite/alginate/chitosan composite scaffolds for bone tissue engineering. , 2015, Materials science & engineering. C, Materials for biological applications.

[24]  María Vallet-Regí,et al.  Setting Behavior and in Vitro Bioactivity of Hydroxyapatite/Calcium Sulfate Cements , 2002 .

[25]  Jiang Chang,et al.  Synthesis of a Well‐Ordered Mesoporous 58S Bioactive Glass by a Simple Method , 2011 .

[26]  Lei Peng,et al.  Engineering scaffolds integrated with calcium sulfate and oyster shell for enhanced bone tissue regeneration. , 2014, ACS applied materials & interfaces.

[27]  Changqing Zhang,et al.  Three-dimensional printed strontium-containing mesoporous bioactive glass scaffolds for repairing rat critical-sized calvarial defects. , 2015, Acta biomaterialia.

[28]  Amit Bandyopadhyay,et al.  Effects of silica and zinc oxide doping on mechanical and biological properties of 3D printed tricalcium phosphate tissue engineering scaffolds. , 2012, Dental materials : official publication of the Academy of Dental Materials.

[29]  D. Zhao,et al.  The in-vitro bioactivity of mesoporous bioactive glasses. , 2006, Biomaterials.

[30]  Chengtie Wu,et al.  In vitro assessment of three-dimensionally plotted nagelschmidtite bioceramic scaffolds with varied macropore morphologies. , 2014, Acta biomaterialia.

[31]  S. Ferrari,et al.  Author contributions , 2021 .

[32]  Xiaolin Li,et al.  Three-dimensional poly (ε-caprolactone)/hydroxyapatite/collagen scaffolds incorporating bone marrow mesenchymal stem cells for the repair of bone defects , 2016, Biomedical materials.

[33]  Chengtie Wu,et al.  Biological response of human bone cells to zinc-modified Ca-Si-based ceramics. , 2008, Acta biomaterialia.

[34]  Changqing Zhang,et al.  Three-dimensional printing of strontium-containing mesoporous bioactive glass scaffolds for bone regeneration. , 2014, Acta biomaterialia.

[35]  David A Puleo,et al.  Calcium sulfate: Properties and clinical applications. , 2009, Journal of biomedical materials research. Part B, Applied biomaterials.

[36]  Stefan Kaskel,et al.  Preparation, characterization and in vitro bioactivity of mesoporous bioactive glasses (MBGs) scaffolds for bone tissue engineering , 2008 .

[37]  Dong Zhai,et al.  Three-Dimensional Printing of Hollow-Struts-Packed Bioceramic Scaffolds for Bone Regeneration. , 2015, ACS applied materials & interfaces.

[38]  A. Coetzee Regeneration of bone in the presence of calcium sulfate. , 1980, Archives of otolaryngology.

[39]  Jiang Chang,et al.  Reconstruction of calvarial defect of rabbits using porous calcium silicate bioactive ceramics. , 2008, Biomaterials.

[40]  Ramille N Shah,et al.  Three-dimensional printing of soy protein scaffolds for tissue regeneration. , 2013, Tissue engineering. Part C, Methods.

[41]  Gianaurelio Cuniberti,et al.  Three-dimensional printing of hierarchical and tough mesoporous bioactive glass scaffolds with a controllable pore architecture, excellent mechanical strength and mineralization ability. , 2011, Acta biomaterialia.

[42]  Jiang Chang,et al.  Self-setting properties and in vitro bioactivity of calcium sulfate hemihydrate-tricalcium silicate composite bone cements. , 2007, Acta biomaterialia.

[43]  N. Annabi,et al.  Fabrication of poly-DL-lactide/polyethylene glycol scaffolds using the gas foaming technique. , 2012, Acta biomaterialia.

[44]  Wim E Hennink,et al.  In vivo biocompatibility and biodegradation of 3D-printed porous scaffolds based on a hydroxyl-functionalized poly(ε-caprolactone). , 2012, Biomaterials.

[45]  Jiang Chang,et al.  Well-ordered mesoporous bioactive glasses (MBG): a promising bioactive drug delivery system. , 2006, Journal of controlled release : official journal of the Controlled Release Society.