Hyperelastic "bone": A highly versatile, growth factor-free, osteoregenerative, scalable, and surgically friendly biomaterial.
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(lactic-co-glycolic acid), could be rapidly three-dimensionally (3D) printed (up to 275 cm(3)/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.
Department of Materials Science and Engineering, Northwestern University, Evanston, IL 60208, USA. Simpson Querrey Institute for BioNanotechnology, Northwestern University, Chicago, IL 60611, USA.
Adam E
AE
Jakus
Simpson Querrey Institute for BioNanotechnology, Northwestern University, Chicago, IL 60611, USA. Department of Biomedical Engineering, Northwestern University, Evanston, IL 60208, USA.
Alexandra L
AL
Rutz
Department of Surgery, Division of Plastic and Reconstructive Surgery, Northwestern University, Chicago, IL 60611, USA.
Sumanas W
SW
Jordan
Department of Orthopaedic Surgery, Northwestern University, Chicago, IL 60611, USA.
Abhishek
A
Kannan
Department of Orthopaedic Surgery, Northwestern University, Chicago, IL 60611, USA.
Sean M
SM
Mitchell
Department of Orthopaedic Surgery, Northwestern University, Chicago, IL 60611, USA.
Chawon
C
Yun
Department of Materials Science and Engineering, Northwestern University, Evanston, IL 60208, USA. Simpson Querrey Institute for BioNanotechnology, Northwestern University, Chicago, IL 60611, USA.
Katie D
KD
Koube
Department of Materials Science and Engineering, Northwestern University, Evanston, IL 60208, USA. Simpson Querrey Institute for BioNanotechnology, Northwestern University, Chicago, IL 60611, USA.
Sung C
SC
Yoo
Department of Veterinary Pathobiology, University of Illinois, Urbana, IL 61822, USA.
Herbert E
HE
Whiteley
Department of Otolaryngology-Head and Neck Surgery, Northwestern University, Chicago, IL 60611, USA.
Claus-Peter
CP
Richter
Department of Surgery, Division of Plastic and Reconstructive Surgery, Northwestern University, Chicago, IL 60611, USA.
Robert D
RD
Galiano
Simpson Querrey Institute for BioNanotechnology, Northwestern University, Chicago, IL 60611, USA. Department of Orthopaedic Surgery, Northwestern University, Chicago, IL 60611, USA.
Wellington K
WK
Hsu
Department of Cell and Molecular Biology, Northwestern University, Chicago, IL 60611, USA.
Stuart R
SR
Stock
Simpson Querrey Institute for BioNanotechnology, Northwestern University, Chicago, IL 60611, USA. Department of Orthopaedic Surgery, Northwestern University, Chicago, IL 60611, USA.
Erin L
EL
Hsu
Department of Materials Science and Engineering, Northwestern University, Evanston, IL 60208, USA. Simpson Querrey Institute for BioNanotechnology, Northwestern University, Chicago, IL 60611, USA. Department of Biomedical Engineering, Northwestern University, Evanston, IL 60208, USA. Department of Surgery, Division of Organ Transplantation, Northwestern University, Chicago, IL 60611, USA. ramille-shah@northwestern.edu.
Ramille N
RN
Shah
D000818:Animals; D001672:Biocompatible Materials / Q000494:pharmacology*; D001861:Bone Regeneration / Q000187:drug effects*; D001842:Bone and Bones / Q000502:physiology*; D004195:Disease Models, Animal; D004548:Elasticity; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000494:pharmacology; D008251:Macaca; D008422:Materials Testing; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000187:drug effects; D051379:Mice; D019637:Orthopedic Procedures; D066330:Printing, Three-Dimensional; D051381:Rats; D012886:Skull / Q000473:pathology; D013123:Spinal Fusion; D040521:Subcutaneous Tissue / Q000187:drug effects; D054457:Tissue Scaffolds / Q000737:chemistry
D001672:Biocompatible Materials; D036341:Intercellular Signaling Peptides and Proteins