TY - JOUR
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 W.
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 N.
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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U2 - 10.1126/scitranslmed.aaf7704
DO - 10.1126/scitranslmed.aaf7704
M3 - Article
C2 - 27683552
AN - SCOPUS:84989940420
SN - 1946-6234
VL - 8
JO - Science Translational Medicine
JF - Science Translational Medicine
IS - 358
M1 - 358ra128
ER -