Hyperelastic "bone"

A highly versatile, growth factor-free, osteoregenerative, scalable, and surgically friendly biomaterial

Adam E. Jakus, Alexandra L. Rutz, Sumanas Wanant Jordan, Abhishek Kannan, Sean M. Mitchell, Chawon Yun, Katie D. Koube, Sung C. Yoo, Herbert E. Whiteley, Claus-Peter Richter, Robert D Galiano, Wellington K Hsu, Stuart R Stock, Erin L Hsu, Ramille Nirav Shah*

*Corresponding author for this work

Research output: Contribution to journalArticle

71 Citations (Scopus)

Abstract

Despite substantial attention given to the development of osteoregenerative biomaterials, severe deficiencies remain in current products. These limitations include an inability to adequately, rapidly, and reproducibly regenerate new bone; high costs and limited manufacturing capacity; and lack of surgical ease of handling. To address these shortcomings, we generated a new, synthetic osteoregenerative biomaterial, hyperelastic "bone" (HB). HB, which is composed of 90 weight % (wt %) hydroxyapatite and 10 wt % polycaprolactone or poly(lacticco- glycolic acid), could be rapidly three-dimensionally (3D) printed (up to 275 cm3/hour) from room temperature extruded liquid inks. The resulting 3D-printed HB exhibited elastic mechanical properties (32 to 67% strain to failure, ~4 to 11 MPa elastic modulus), was highly absorbent (50% material porosity), supported cell viability and proliferation, and induced osteogenic differentiation of bone marrow-derived human mesenchymal stem cells cultured in vitro over 4 weeks without any osteo-inducing factors in the medium. We evaluated HB in vivo in a mouse subcutaneous implant model for material biocompatibility (7 and 35 days), in a rat posterolateral spinal fusion model for new bone formation (8 weeks), and in a large, non-human primate calvarial defect case study (4 weeks). HB did not elicit a negative immune response, became vascularized, quickly integrated with surrounding tissues, and rapidly ossified and supported new bone growth without the need for added biological factors.

Original languageEnglish (US)
Article number358ra128
JournalScience translational medicine
Volume8
Issue number358
DOIs
StatePublished - Sep 28 2016

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Biocompatible Materials
Intercellular Signaling Peptides and Proteins
Bone and Bones
glycolic acid
Weights and Measures
Spinal Fusion
Ink
Elastic Modulus
Porosity
Bone Development
Biological Factors
Durapatite
Mesenchymal Stromal Cells
Osteogenesis
Primates
Cell Survival
Bone Marrow
Cell Proliferation
Costs and Cost Analysis
Temperature

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Jakus, Adam E. ; Rutz, Alexandra L. ; Jordan, Sumanas Wanant ; Kannan, Abhishek ; Mitchell, Sean M. ; Yun, Chawon ; Koube, Katie D. ; Yoo, Sung C. ; Whiteley, Herbert E. ; Richter, Claus-Peter ; Galiano, Robert D ; Hsu, Wellington K ; Stock, Stuart R ; Hsu, Erin L ; Shah, Ramille Nirav. / Hyperelastic "bone" : A highly versatile, growth factor-free, osteoregenerative, scalable, and surgically friendly biomaterial. In: Science translational medicine. 2016 ; Vol. 8, No. 358.
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Hyperelastic "bone" : A highly versatile, growth factor-free, osteoregenerative, scalable, and surgically friendly biomaterial. / Jakus, Adam E.; Rutz, Alexandra L.; Jordan, Sumanas Wanant; Kannan, Abhishek; Mitchell, Sean M.; Yun, Chawon; Koube, Katie D.; Yoo, Sung C.; Whiteley, Herbert E.; Richter, Claus-Peter; Galiano, Robert D; Hsu, Wellington K; Stock, Stuart R; Hsu, Erin L; Shah, Ramille Nirav.

In: Science translational medicine, Vol. 8, No. 358, 358ra128, 28.09.2016.

Research output: Contribution to journalArticle

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T1 - Hyperelastic "bone"

T2 - A highly versatile, growth factor-free, osteoregenerative, scalable, and surgically friendly biomaterial

AU - Jakus, Adam E.

AU - Rutz, Alexandra L.

AU - Jordan, Sumanas Wanant

AU - Kannan, Abhishek

AU - Mitchell, Sean M.

AU - Yun, Chawon

AU - Koube, Katie D.

AU - Yoo, Sung C.

AU - Whiteley, Herbert E.

AU - Richter, Claus-Peter

AU - Galiano, Robert D

AU - Hsu, Wellington K

AU - Stock, Stuart R

AU - Hsu, Erin L

AU - Shah, Ramille Nirav

PY - 2016/9/28

Y1 - 2016/9/28

N2 - Despite substantial attention given to the development of osteoregenerative biomaterials, severe deficiencies remain in current products. These limitations include an inability to adequately, rapidly, and reproducibly regenerate new bone; high costs and limited manufacturing capacity; and lack of surgical ease of handling. To address these shortcomings, we generated a new, synthetic osteoregenerative biomaterial, hyperelastic "bone" (HB). HB, which is composed of 90 weight % (wt %) hydroxyapatite and 10 wt % polycaprolactone or poly(lacticco- glycolic acid), could be rapidly three-dimensionally (3D) printed (up to 275 cm3/hour) from room temperature extruded liquid inks. The resulting 3D-printed HB exhibited elastic mechanical properties (32 to 67% strain to failure, ~4 to 11 MPa elastic modulus), was highly absorbent (50% material porosity), supported cell viability and proliferation, and induced osteogenic differentiation of bone marrow-derived human mesenchymal stem cells cultured in vitro over 4 weeks without any osteo-inducing factors in the medium. We evaluated HB in vivo in a mouse subcutaneous implant model for material biocompatibility (7 and 35 days), in a rat posterolateral spinal fusion model for new bone formation (8 weeks), and in a large, non-human primate calvarial defect case study (4 weeks). HB did not elicit a negative immune response, became vascularized, quickly integrated with surrounding tissues, and rapidly ossified and supported new bone growth without the need for added biological factors.

AB - Despite substantial attention given to the development of osteoregenerative biomaterials, severe deficiencies remain in current products. These limitations include an inability to adequately, rapidly, and reproducibly regenerate new bone; high costs and limited manufacturing capacity; and lack of surgical ease of handling. To address these shortcomings, we generated a new, synthetic osteoregenerative biomaterial, hyperelastic "bone" (HB). HB, which is composed of 90 weight % (wt %) hydroxyapatite and 10 wt % polycaprolactone or poly(lacticco- glycolic acid), could be rapidly three-dimensionally (3D) printed (up to 275 cm3/hour) from room temperature extruded liquid inks. The resulting 3D-printed HB exhibited elastic mechanical properties (32 to 67% strain to failure, ~4 to 11 MPa elastic modulus), was highly absorbent (50% material porosity), supported cell viability and proliferation, and induced osteogenic differentiation of bone marrow-derived human mesenchymal stem cells cultured in vitro over 4 weeks without any osteo-inducing factors in the medium. We evaluated HB in vivo in a mouse subcutaneous implant model for material biocompatibility (7 and 35 days), in a rat posterolateral spinal fusion model for new bone formation (8 weeks), and in a large, non-human primate calvarial defect case study (4 weeks). HB did not elicit a negative immune response, became vascularized, quickly integrated with surrounding tissues, and rapidly ossified and supported new bone growth without the need for added biological factors.

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