3D Printed Multifunctional Ti6Al4V-Based Hybrid Scaffold for the Management of Osteosarcoma.

Osteosarcoma is a challenging bone disease which is commonly associated with critical sized bone defect and cancer recurrence. Here we designed and developed a multi-functional, hierarchical structured bone scaffold which can meet the demanding requirements for osteosarcoma management. This is the first 3D printed Ti6Al4V scaffold with hydrothermally induced TiO2/TiP coating offering its unique photothermal conversion property for bone cancer ablation. The scaffold is also infused with drug laden gelatin/hydroxyapatite nanocomposite, which provides the ideal porous structure for cell adhesion / bone ingrowth and promotes bone regeneration. The scaffold has been thoroughly characterized by SEM/EDX, TEM, XPS, XRD, TGA and UV-vis, and its in vitro bone cancer ablation efficiency has been validated using MG-63 cells. The hybrid scaffold showed excellent biocompatibility and its osteointegration function has been demonstrated using an animal model. Highlight • The first Ti6Al4V based bone scaffold with hierarchical microstructure and multi-functions targeting osteosarcoma management and bone defect repair. • The first time TiO2/TiP coating has been deployed for photothermal cancer ablation. • The infused gelatin/hydroxyapatite nanocomposite provides favorable drug release and bone regeneration property which has been validated in vitro and in vivo.

[1]  Emeka Nkenke,et al.  Autogenous bone harvesting and grafting in advanced jaw resorption: morbidity, resorption and implant survival. , 2014, European journal of oral implantology.

[2]  Afra Hadjizadeh,et al.  Chitosan-gelatin porous scaffold incorporated with Chitosan nanoparticles for growth factor delivery in tissue engineering. , 2018, Carbohydrate polymers.

[3]  Dongle Wu,et al.  3D-printed Ti6Al4V scaffolds coated with freeze-dried platelet-rich plasma as bioactive interface for enhancing osseointegration in osteoporosis , 2020 .

[4]  Tae-Geon Kwon,et al.  Effects of phosphoric acid treatment of titanium surfaces on surface properties, osteoblast response and removal of torque forces. , 2010, Acta biomaterialia.

[5]  C. Shuai,et al.  Mg bone implant: Features, developments and perspectives , 2020 .

[6]  C. McCoy,et al.  Nanoscale Hybrid Coating Enables Multifunctional Tissue Scaffold for Potential Multimodal Therapeutic Applications. , 2019, ACS applied materials & interfaces.

[7]  S. Burchill,et al.  ABCG1 and Pgp identify drug resistant, self-renewing osteosarcoma cells. , 2019, Cancer letters.

[8]  Changsheng Liu,et al.  The Horizon of Materiobiology: A Perspective on Material-Guided Cell Behaviors and Tissue Engineering. , 2017, Chemical reviews.

[9]  Q. Wei,et al.  3D-printed porous titanium scaffolds incorporating niobium for high bone regeneration capacity , 2020 .

[10]  Yingjun Wang,et al.  Hollow hydroxyapatite microsphere: a promising carrier for bone tissue engineering , 2016, Journal of microencapsulation.

[11]  A. Khademhosseini,et al.  Bioactive Silicate Nanoplatelets for Osteogenic Differentiation of Human Mesenchymal Stem Cells , 2013, Advanced materials.

[12]  Dan Sun,et al.  Graded/Gradient Porous Biomaterials , 2009, Materials.

[13]  Xiaolong Zhu,et al.  Characterization of nano hydroxyapatite/collagen surfaces and cellular behaviors. , 2006, Journal of biomedical materials research. Part A.

[14]  Chun Gwon Park,et al.  Bioabsorbable bone plates enabled with local, sustained delivery of alendronate for bone regeneration. , 2016, Journal of controlled release : official journal of the Controlled Release Society.

[15]  S. Ferrari,et al.  Postrelapse survival in osteosarcoma of the extremities: prognostic factors for long-term survival. , 2003, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[16]  Yufeng Zheng,et al.  Tailored Surface Treatment of 3D Printed Porous Ti6Al4V by Microarc Oxidation for Enhanced Osseointegration via Optimized Bone In-Growth Patterns and Interlocked Bone/Implant Interface. , 2016, ACS applied materials & interfaces.

[17]  Chunqiu Zhang,et al.  Mechanical behavior of a titanium alloy scaffold mimicking trabecular structure , 2020, Journal of Orthopaedic Surgery and Research.

[18]  R. Adler.  Osteoporosis in men: a review , 2014, Bone Research.

[19]  M. Montjovent,et al.  UvA-DARE ( Digital Academic Repository ) VEGF incorporated into calcium phosphate ceramics promotes vascularisation and bone formation in vivo , 2010 .

[20]  Chengtie Wu,et al.  A hydrogenated black TiO2 coating with excellent effects for photothermal therapy of bone tumor and bone regeneration. , 2019, Materials science & engineering. C, Materials for biological applications.

[21]  Yong Hu,et al.  Dynamically tuning near-infrared-induced photothermal performances of TiO2 nanocrystals by Nb doping for imaging-guided photothermal therapy of tumors. , 2017, Nanoscale.

[22]  Yubao Li,et al.  Promoting Osseointegration of Ti Implants through Micro/Nanoscaled Hierarchical Ti Phosphate/Ti Oxide Hybrid Coating. , 2018, ACS nano.

[23]  Ping Liu,et al.  3D printed biodegradable implants as an individualized drug delivery system for local chemotherapy of osteosarcoma , 2020 .

[24]  Xing‐dong Zhang,et al.  Photo-cross-linkable methacrylated gelatin and hydroxyapatite hybrid hydrogel for modularly engineering biomimetic osteon. , 2015, ACS applied materials & interfaces.

[25]  Yubao Li,et al.  Multifunctional load-bearing hybrid hydrogel with combined drug release and photothermal conversion functions , 2020, NPG Asia Materials.

[26]  F. Weber,et al.  The optimal microarchitecture of 3D-printed β-TCP bone substitutes for vertical bone augmentation differs from that for osteoconduction , 2021, Materials & Design.

[27]  Zhihong Wu,et al.  A novel hybrid 3D-printed titanium scaffold for osteogenesis in a rabbit calvarial defect model. , 2018, American journal of translational research.

[28]  M. Fernández-Gutiérrez,et al.  Bio-safe fabrication of PLA scaffolds for bone tissue engineering by combining phase separation, porogen leaching and scCO2 drying , 2015 .

[29]  Soong Ho Um,et al.  BMP-2 peptide-functionalized nanopatterned substrates for enhanced osteogenic differentiation of human mesenchymal stem cells. , 2013, Biomaterials.

[30]  Yingjun Wang,et al.  Hierarchical porous hydroxyapatite microsphere as drug delivery carrier , 2013 .

[31]  Meng Zhang,et al.  Three-Dimensional-Printed Bioceramic Scaffolds with Osteogenic Activity for Simultaneous Photo/Magnetothermal Therapy of Bone Tumors. , 2019, ACS biomaterials science & engineering.

[32]  Yongxiang Luo,et al.  3D printing of concentrated alginate/gelatin scaffolds with homogeneous nano apatite coating for bone tissue engineering , 2018 .

[33]  L. Raimondi,et al.  Relevance of 3d culture systems to study osteosarcoma environment , 2018, Journal of Experimental & Clinical Cancer Research.

[34]  J. Weng,et al.  Fabrication of TiO2 nanotubes on porous titanium scaffold and biocompatibility evaluation in vitro and in vivo. , 2012, Journal of biomedical materials research. Part A.

[35]  M. Niinomi,et al.  Experiment study on fracture fixation with low rigidity titanium alloy , 2008, Journal of materials science. Materials in medicine.

[36]  C. Elias,et al.  Mechanical properties, surface morphology and stability of a modified commercially pure high strength titanium alloy for dental implants. , 2015, Dental materials : official publication of the Academy of Dental Materials.

[37]  Xingdong Zhang,et al.  3D printing of calcium phosphate scaffolds with controlled release of antibacterial functions for jaw bone repair , 2020 .

[38]  Xing-yu Zhao,et al.  Combining photothermal ablation-based vaccine with immune checkpoint blockade for synergistic osteosarcoma immunotherapy , 2021 .

[39]  M. Shieh,et al.  Platinum(II) Drug-Loaded Gold Nanoshells for Chemo-Photothermal Therapy in Colorectal Cancer. , 2020, ACS applied materials & interfaces.

[40]  Geng Li,et al.  Degradation pattern of porous CaCO3 and hydroxyapatite microspheres in vitro and in vivo for potential application in bone tissue engineering. , 2016, Colloids and surfaces. B, Biointerfaces.

[41]  Shujun Li,et al.  Bioinspired Fabrication of Calcium-doped TiP Coating with Nano-fibrous Microstructure to Accelerate Osseointegration. , 2020, Bioconjugate chemistry.

[42]  Yubao Li,et al.  The custom making of hierarchical micro/nanoscaled titanium phosphate coatings and their formation mechanism analysis , 2019, RSC advances.

[43]  Ying-Jie Zhu,et al.  Microwave-assisted synthesis of hydroxyapatite hollow microspheres in aqueous solution , 2011 .

[44]  Guohua Jiang,et al.  Hydrothermal fabrication of porous hollow hydroxyapatite microspheres for a drug delivery system. , 2016, Materials science & engineering. C, Materials for biological applications.

[45]  L. Cui,et al.  Salvianolic acid B promotes osteogenesis of human mesenchymal stem cells through activating ERK signaling pathway. , 2014, The international journal of biochemistry & cell biology.

[46]  Li Zhang,et al.  Atmospheric Pressure Plasma Synthesized Gold Nanoparticle/Carbon Nanotube Hybrids for Photo-thermal Conversion , 2019 .

[47]  Yubao Li,et al.  Conducting Polyetheretherketone Nanocomposites with an Electrophoretically Deposited Bioactive Coating for Bone Tissue Regeneration and Multimodal Therapeutic Applications. , 2020, ACS applied materials & interfaces.

[48]  K. Su,et al.  Recent advances in the use of gelatin in biomedical research , 2015, Biotechnology Letters.