Correction of large jawbone defect in the mouse using immature osteoblast–like cells and a 3D polylactic acid scaffold

Abstract Bone tissue engineering has been developed using a combination of mesenchymal stem cells (MSCs) and calcium phosphate–based scaffolds. However, these complexes cannot regenerate large jawbone defects. To overcome this limitation of MSCs and ceramic scaffolds, a novel bone regeneration technology must be developed using cells possessing high bone forming ability and a scaffold that provides space for vertical bone augmentation. To approach this problem in our study, we developed alveolar bone–derived immature osteoblast–like cells (HAOBs), which have the bone regenerative capacity to correct a large bone defect when used as a grafting material in combination with polylactic acid fibers that organize the 3D structure and increase the strength of the scaffold material (3DPL). HAOB-3DPL constructs could not regenerate bone via xenogeneic transplantation in a micromini pig alveolar bone defect model. However, the autogenic transplantation of mouse calvaria–derived immature osteoblast–like cells (MCOBs) isolated using the identical protocol for HAOBs and mixed with 3DPL scaffolds successfully regenerated the bone in a large jawbone defect mouse model, compared to the 3DPL scaffold alone. Nanoindentation analysis indicated that the regenerated bone had a similar micromechanical strength to native bone. In addition, this MCOB-3DPL regenerated bone possesses osseointegration ability wherein a direct structural connection is established with the titanium implant surface. Hence, a complex formed between a 3DPL scaffold and immature osteoblast–like cells such as MCOBs represents a novel bone tissue engineering approach that enables the formation of vertical bone with the micromechanical properties required to treat large bone defects.

[1]  Koichiro Hayashi,et al.  Carbonate apatite artificial bone , 2021, Science and technology of advanced materials.

[2]  K. Pramanik,et al.  Electrospun scaffold for bone regeneration , 2021, International Journal of Polymeric Materials and Polymeric Biomaterials.

[3]  N. López-Valverde,et al.  Effectiveness of Antibacterial Surfaces in Osseointegration of Titanium Dental Implants: A Systematic Review , 2021, Antibiotics.

[4]  A. Shrestha,et al.  Biomaterial Properties Modulating Bone Regeneration. , 2021, Macromolecular bioscience.

[5]  Y. Yusuf,et al.  Bioceramic hydroxyapatite-based scaffold with a porous structure using honeycomb as a natural polymeric Porogen for bone tissue engineering , 2021, Biomaterials Research.

[6]  Lianfei Wang,et al.  Horizontal bone augmentation and simultaneous implant placement using xenogeneic bone rings technique: a retrospective clinical study , 2020, Scientific Reports.

[7]  Miaoda Shen,et al.  Bone tissue regeneration: The role of finely tuned pore architecture of bioactive scaffolds before clinical translation , 2020, Bioactive materials.

[8]  Jin-Yuan Guo,et al.  Mega-oss and Mega-TCP versus Bio-Oss granules fixed by alginate gel for bone regeneration , 2020, BDJ Open.

[9]  R. Levato,et al.  Endochondral Bone Regeneration by Non-autologous Mesenchymal Stem Cells , 2020, Frontiers in Bioengineering and Biotechnology.

[10]  J. Locs,et al.  In vitro comparison of 3D printed polylactic acid/hydroxyapatite and polylactic acid/bioglass composite scaffolds: Insights into materials for bone regeneration. , 2020, Journal of the mechanical behavior of biomedical materials.

[11]  Koichiro Hayashi,et al.  Granular Honeycombs Composed of Carbonate Apatite, Hydroxyapatite, and β-Tricalcium Phosphate as Bone Graft Substitutes: Effects of Composition on Bone Formation and Maturation. , 2020, ACS applied bio materials.

[12]  Nam-Trung Nguyen,et al.  Porous scaffolds for bone regeneration , 2020 .

[13]  Yan Liu,et al.  Effect of the nano/microscale structure of biomaterial scaffolds on bone regeneration , 2020, International Journal of Oral Science.

[14]  S. Marchianò,et al.  Cardiomyocyte maturation: advances in knowledge and implications for regenerative medicine , 2020, Nature Reviews Cardiology.

[15]  T. Kawai,et al.  Clinical study of octacalcium phosphate and collagen composite in oral and maxillofacial surgery , 2020, Journal of tissue engineering.

[16]  Y. Yahata,et al.  Comparison of the vertical bone defect healing abilities of carbonate apatite, β-tricalcium phosphate, hydroxyapatite and bovine-derived heterogeneous bone. , 2019, Dental materials journal.

[17]  Richard Weinkamer,et al.  Mechanoregulation of Bone Remodeling and Healing as Inspiration for Self-Repair in Materials , 2019, Biomimetics.

[18]  Eamon J. Sheehy,et al.  Biomaterial-based endochondral bone regeneration: a shift from traditional tissue engineering paradigms to developmentally inspired strategies , 2019, Materials today. Bio.

[19]  J. Ryan,et al.  Polymer scaffold architecture is a key determinant in mast cell inflammatory and angiogenic responses. , 2019, Journal of biomedical materials research. Part A.

[20]  I. Asahina,et al.  First clinical application of octacalcium phosphate collagen composite on bone regeneration in maxillary sinus floor augmentation: A prospective, single-arm, open-label clinical trial. , 2019, Journal of biomedical materials research. Part B, Applied biomaterials.

[21]  A. Ignatius,et al.  Autologous Mesenchymal Stroma Cells Are Superior to Allogeneic Ones in Bone Defect Regeneration , 2018, International journal of molecular sciences.

[22]  R. Wong,et al.  Unraveling the mechanical strength of biomaterials used as a bone scaffold in oral and maxillofacial defects , 2018, Oral Science International.

[23]  Alexander Schramm,et al.  Autogenous bone grafts in oral implantology—is it still a “gold standard”? A consecutive review of 279 patients with 456 clinical procedures , 2017, International Journal of Implant Dentistry.

[24]  A. Ignatius,et al.  Mechanobiology of bone remodeling and fracture healing in the aged organism , 2016, Innovative surgical sciences.

[25]  K. Shinomiya,et al.  Efficacy and safety of porous hydroxyapatite/type 1 collagen composite implantation for bone regeneration: A randomized controlled study. , 2016, Journal of orthopaedic science : official journal of the Japanese Orthopaedic Association.

[26]  U. Stachewicz,et al.  3D imaging of cell interactions with electrospun PLGA nanofiber membranes for bone regeneration. , 2015, Acta biomaterialia.

[27]  Y. Lv,et al.  3D Scaffolds with Different Stiffness but the Same Microstructure for Bone Tissue Engineering. , 2015, ACS applied materials & interfaces.

[28]  Cato T Laurencin,et al.  Biomaterials for Bone Regenerative Engineering , 2015, Advanced healthcare materials.

[29]  W. Grayson,et al.  Stromal cells and stem cells in clinical bone regeneration , 2015, Nature Reviews Endocrinology.

[30]  T. Yoneda,et al.  Isolation and characterization of the human immature osteoblast culture system from the alveolar bones of aged donors for bone regeneration therapy , 2014, Expert opinion on biological therapy.

[31]  M. Stevens,et al.  Cotton-wool-like bioactive glasses for bone regeneration. , 2014, Acta biomaterialia.

[32]  L. Rimondini,et al.  Analysis of human alveolar osteoblast behavior on a nano-hydroxyapatite substrate: an in vitro study , 2014, BMC Oral Health.

[33]  L. Rimondini,et al.  Analysis of human alveolar osteoblast behavior on a nano-hydroxyapatite substrate: an in vitro study , 2014, BMC oral health.

[34]  Cleo Choong,et al.  Three-dimensional scaffolds for tissue engineering applications: role of porosity and pore size. , 2013, Tissue engineering. Part B, Reviews.

[35]  M. Sakane,et al.  Histological Analysis of Bone Bonding and Ingrowth into Connected Porous Hydroxyapatite Spacers in Spinal Surgery , 2012 .

[36]  J. Jansen,et al.  Evaluation of bone regeneration using the rat critical size calvarial defect , 2012, Nature Protocols.

[37]  R. Othman,et al.  Macroporous bioceramics: A remarkable material for bone regeneration , 2012, Journal of biomaterials applications.

[38]  G. Warnock,et al.  Maturation of Human Embryonic Stem Cell–Derived Pancreatic Progenitors Into Functional Islets Capable of Treating Pre-existing Diabetes in Mice , 2012, Diabetes.

[39]  Warren L. Grayson,et al.  Engineering bone tissue from human embryonic stem cells , 2012, Proceedings of the National Academy of Sciences.

[40]  Heidi-Lynn Ploeg,et al.  Mechanical characterization of injection-molded macro porous bioceramic bone scaffolds. , 2012, Journal of the mechanical behavior of biomedical materials.

[41]  J. Planell,et al.  A short review: Recent advances in electrospinning for bone tissue regeneration , 2012, Journal of tissue engineering.

[42]  Guillaume Haiat,et al.  Nanoindentation measurements of biomechanical properties in mature and newly formed bone tissue surrounding an implant. , 2012, Journal of biomechanical engineering.

[43]  A. Weiss,et al.  Increasing the pore size of electrospun scaffolds. , 2011, Tissue engineering. Part B, Reviews.

[44]  Shicheng Wei,et al.  Electrospun PCL/PLA/HA based nanofibers as scaffold for osteoblast-like cells. , 2010, Journal of nanoscience and nanotechnology.

[45]  F. O'Brien,et al.  Addition of hydroxyapatite improves stiffness, interconnectivity and osteogenic potential of a highly porous collagen-based scaffold for bone tissue regeneration. , 2010, European cells & materials.

[46]  David J. Mooney,et al.  Harnessing Traction-Mediated Manipulation of the Cell-Matrix Interface to Control Stem Cell Fate , 2010, Nature materials.

[47]  P. Kasten,et al.  Transplantation of human mesenchymal stem cells in a non-autogenous setting for bone regeneration in a rabbit critical-size defect model. , 2010, Acta biomaterialia.

[48]  Stefan Milz,et al.  Xenogenic transplantation of human mesenchymal stem cells in a critical size defect of the sheep tibia for bone regeneration. , 2010, Tissue engineering. Part A.

[49]  H. Kim,et al.  Biomimetic approach to dental implants. , 2008, Current pharmaceutical design.

[50]  Molly M Stevens,et al.  Exploring and engineering the cell surface interface. , 2011, Science.