title: Nanoparticulate mineralized collagen scaffolds induce in vivo bone regeneration independent of progenitor cell loading or exogenous growth factor stimulation.
abstract: Current strategies for skeletal regeneration often require co-delivery of scaffold technologies, growth factors, and cellular material. However, isolation and expansion of stem cells can be time consuming, costly, and requires an additional procedure for harvest. Further, the introduction of supraphysiologic doses of growth factors may result in untoward clinical side effects, warranting pursuit of alternative methods for stimulating osteogenesis. In this work, we describe a nanoparticulate mineralized collagen glycosaminoglycan scaffold that induces healing of critical-sized rabbit cranial defects without addition of expanded stem cells or exogenous growth factors. We demonstrate that the mechanism of osteogenic induction corresponds to an increase in canonical BMP receptor signalling secondary to autogenous production of BMP-2 and -9 early and BMP-4 later during differentiation. Thus, nanoparticulate mineralized collagen glycosaminoglycan scaffolds may provide a novel growth factor-free and ex vivo progenitor cell culture-free implantable method for bone regeneration.
authors.affiliation: Division of Plastic and Reconstructive Surgery, UCLA David Geffen School of Medicine, Los Angeles, CA 90095, USA; Division of Plastic and Reconstructive Surgery, Greater Los Angeles VA Healthcare System, Los Angeles, CA 90073, USA; Research Service, Greater Los Angeles VA Healthcare System, Los Angeles, CA 90073, USA.
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Ren
authors.affiliation: Division of Plastic and Reconstructive Surgery, UCLA David Geffen School of Medicine, Los Angeles, CA 90095, USA; Division of Plastic and Reconstructive Surgery, Greater Los Angeles VA Healthcare System, Los Angeles, CA 90073, USA; Research Service, Greater Los Angeles VA Healthcare System, Los Angeles, CA 90073, USA.
authors.forename: Victor
authors.initials: V
authors.lastname: Tu
authors.affiliation: Research Service, Greater Los Angeles VA Healthcare System, Los Angeles, CA 90073, USA.
authors.forename: David
authors.initials: D
authors.lastname: Bischoff
authors.affiliation: Department of Chemical and Biomolecular Engineering, Institute for Genomic Biology, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA.
authors.forename: Daniel W
authors.initials: DW
authors.lastname: Weisgerber
authors.affiliation: Department of Pathology, Greater Los Angeles VA Healthcare System, Los Angeles, CA 90073, USA.
authors.forename: Michael S
authors.initials: MS
authors.lastname: Lewis
authors.affiliation: Research Service, Greater Los Angeles VA Healthcare System, Los Angeles, CA 90073, USA.
authors.forename: Dean T
authors.initials: DT
authors.lastname: Yamaguchi
authors.affiliation: Division of Plastic and Reconstructive Surgery, UCLA David Geffen School of Medicine, Los Angeles, CA 90095, USA; Division of Plastic and Reconstructive Surgery, Greater Los Angeles VA Healthcare System, Los Angeles, CA 90073, USA.
authors.forename: Timothy A
authors.initials: TA
authors.lastname: Miller
authors.affiliation: Department of Chemical and Biomolecular Engineering, Institute for Genomic Biology, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA.
authors.forename: Brendan A C
authors.initials: BA
authors.lastname: Harley
authors.affiliation: Division of Plastic and Reconstructive Surgery, UCLA David Geffen School of Medicine, Los Angeles, CA 90095, USA; Division of Plastic and Reconstructive Surgery, Greater Los Angeles VA Healthcare System, Los Angeles, CA 90073, USA; Research Service, Greater Los Angeles VA Healthcare System, Los Angeles, CA 90073, USA. Electronic address: justine@ucla.edu.
authors.forename: Justine C
authors.initials: JC
authors.lastname: Lee
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology; D019485:Bone Morphogenetic Proteins / Q000378:metabolism; D001861:Bone Regeneration; D018786:Bone Substitutes / Q000737:chemistry / Q000627:therapeutic use*; D002478:Cells, Cultured; D003094:Collagen / Q000737:chemistry / Q000627:therapeutic use*; D017102:Fracture Healing; D006025:Glycosaminoglycans / Q000737:chemistry / Q000627:therapeutic use; D053758:Nanoparticles / Q000737:chemistry / Q000627:therapeutic use*; D010012:Osteogenesis; D011817:Rabbits; D015398:Signal Transduction; D012886:Skull / Q000293:injuries* / Q000473:pathology / Q000502:physiology; D017154:Stromal Cells / Q000166:cytology; D054457:Tissue Scaffolds / Q000737:chemistry*
chemical_list: D019485:Bone Morphogenetic Proteins; D018786:Bone Substitutes; D006025:Glycosaminoglycans; D003094:Collagen
keywords: Biomimetic material; Bone regeneration; Nanoparticulate mineralization