title: Simple signaling molecules for inductive bone regenerative engineering.
abstract: With greater than 500,000 orthopaedic procedures performed in the United States each year requiring a bone graft, the development of novel graft materials is necessary. We report that some porous polymer/ceramic composite scaffolds possess intrinsic osteoinductivity as shown through their capacity to induce in vivo host osteoid mineralization and in vitro stem cell osteogenesis making them attractive synthetic bone graft substitutes. It was discovered that certain low crystallinity ceramics partially dissociate into simple signaling molecules (i.e., calcium and phosphate ions) that induce stem cells to endogenously produce their own osteoinductive proteins. Review of the literature has uncovered a variety of simple signaling molecules (i.e., gases, ions, and redox reagents) capable of inducing other desirable stem cell differentiation through endogenous growth factor production. Inductive simple signaling molecules, which we have termed inducerons, represent a paradigm shift in the field of regenerative engineering where they can be utilized in place of recombinant protein growth factors.
authors.affiliation: Department of Chemical Engineering, University of Virginia, Charlottesville, Virginia, United States of America.
authors.forename: Emily K
authors.initials: EK
authors.lastname: Cushnie
authors.affiliation: Institute for Regenerative Engineering, University of Connecticut Health Center, Farmington, Connecticut, United States of America; Raymond and Beverly Sackler Center for Biological, Physical and Engineering Sciences, University of Connecticut Health Center, Farmington, Connecticut, United States of America; Department of Orthopaedic Surgery, University of Connecticut Health Center, Farmington, Connecticut, United States of America.
authors.forename: Bret D
authors.initials: BD
authors.lastname: Ulery
authors.affiliation: School of Medicine, University of Connecticut Health Center, Farmington, Connecticut, United States of America.
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Nelson
authors.affiliation: Institute for Regenerative Engineering, University of Connecticut Health Center, Farmington, Connecticut, United States of America; Raymond and Beverly Sackler Center for Biological, Physical and Engineering Sciences, University of Connecticut Health Center, Farmington, Connecticut, United States of America; Department of Orthopaedic Surgery, University of Connecticut Health Center, Farmington, Connecticut, United States of America.
authors.forename: Meng
authors.initials: M
authors.lastname: Deng
authors.affiliation: Center for Nanotechnology & Advanced Biomaterials, School of Chemical & Biotechnology, SASTRA University, Thanjavur, Tamil Nadu, India.
authors.forename: Swaminathan
authors.initials: S
authors.lastname: Sethuraman
authors.affiliation: Hospital for Special Surgery, New York, New York, United States of America.
authors.forename: Stephen B
authors.initials: SB
authors.lastname: Doty
authors.affiliation: Institute for Regenerative Engineering, University of Connecticut Health Center, Farmington, Connecticut, United States of America; Department of Medicine, Division of Endocrinology, University of Connecticut Health Center, Farmington, Connecticut, United States of America.
authors.forename: Kevin W H
authors.initials: KW
authors.lastname: Lo
authors.affiliation: Institute for Regenerative Engineering, University of Connecticut Health Center, Farmington, Connecticut, United States of America; Raymond and Beverly Sackler Center for Biological, Physical and Engineering Sciences, University of Connecticut Health Center, Farmington, Connecticut, United States of America; Department of Orthopaedic Surgery, University of Connecticut Health Center, Farmington, Connecticut, United States of America; Department of Materials Science and Engineering, University of Connecticut, Storrs, Connecticut, United States of America.
authors.forename: Yusuf M
authors.initials: YM
authors.lastname: Khan
authors.affiliation: Institute for Regenerative Engineering, University of Connecticut Health Center, Farmington, Connecticut, United States of America; Raymond and Beverly Sackler Center for Biological, Physical and Engineering Sciences, University of Connecticut Health Center, Farmington, Connecticut, United States of America; Department of Orthopaedic Surgery, University of Connecticut Health Center, Farmington, Connecticut, United States of America; Department of Chemical and Biomolecular Engineering, University of Connecticut, Storrs, Connecticut, United States of America.
authors.forename: Cato T
authors.initials: CT
authors.lastname: Laurencin
mesh_terms: D000818:Animals; D001861:Bone Regeneration; D018786:Bone Substitutes; D002130:Calcium Phosphates / Q000494:pharmacology*; D002454:Cell Differentiation; D002516:Ceramics; D007477:Ions / Q000494:pharmacology; D008297:Male; D010012:Osteogenesis / Q000187:drug effects*; D011817:Rabbits; D013234:Stem Cells / Q000187:drug effects*; D023822:Tissue Engineering / Q000379:methods*; D054457:Tissue Scaffolds / Q000737:chemistry*
chemical_list: D018786:Bone Substitutes; D002130:Calcium Phosphates; D007477:Ions