title: Multi-protein delivery by nanodiamonds promotes bone formation.
abstract: Bone morphogenetic proteins (BMPs) are well-studied regulators of cartilage and bone development that have been Food and Drug Administration (FDA)-approved for the promotion of bone formation in certain procedures. BMPs are seeing more use in oral and maxillofacial surgeries because of recent FDA approval of InFUSE(®) for sinus augmentation and localized alveolar ridge augmentation. However, the utility of BMPs in medical and dental applications is limited by the delivery method. Currently, BMPs are delivered to the surgical site by the implantation of bulky collagen sponges. Here we evaluate the potential of detonation nanodiamonds (NDs) as a delivery vehicle for BMP-2 and basic fibroblast growth factor (bFGF). Nanodiamonds are biocompatible, 4- to 5-nm carbon nanoparticles that have previously been used to deliver a wide variety of molecules, including proteins and peptides. We find that both BMP-2 and bFGF are readily loaded onto NDs by physisorption, forming a stable colloidal solution, and are triggered to release in slightly acidic conditions. Simultaneous delivery of BMP-2 and bFGF by ND induces differentiation and proliferation in osteoblast progenitor cells. Overall, we find that NDs provide an effective injectable alternative for the delivery of BMP-2 and bFGF to promote bone formation.
authors.affiliation: Biomedical Engineering, Northwestern University, Evanston, IL, USA.
authors.forename: L
authors.initials: L
authors.lastname: Moore
authors.forename: M
authors.initials: M
authors.lastname: Gatica
authors.forename: H
authors.initials: H
authors.lastname: Kim
authors.forename: E
authors.initials: E
authors.lastname: Osawa
authors.forename: D
authors.initials: D
authors.lastname: Ho
mesh_terms: D000469:Alkaline Phosphatase / Q000032:analysis; D001672:Biocompatible Materials / Q000737:chemistry; D055396:Bone Morphogenetic Protein 2 / Q000008:administration & dosage*; D018929:Cell Culture Techniques; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D003102:Colloids / Q000737:chemistry; D004058:Diffusion; D016503:Drug Delivery Systems; D016222:Fibroblast Growth Factor 2 / Q000008:administration & dosage*; D006801:Humans; D032446:Myoblasts / Q000187:drug effects; D058612:Nanodiamonds / Q000737:chemistry*; D010006:Osteoblasts / Q000187:drug effects / Q000502:physiology; D010012:Osteogenesis / Q000187:drug effects*; D010316:Particle Size; D011485:Protein Binding; D017550:Spectroscopy, Fourier Transform Infrared; D013234:Stem Cells / Q000187:drug effects / Q000502:physiology; D013499:Surface Properties
chemical_list: C525718:BMP2 protein, human; D001672:Biocompatible Materials; D055396:Bone Morphogenetic Protein 2; D003102:Colloids; D058612:Nanodiamonds; D016222:Fibroblast Growth Factor 2; D000469:Alkaline Phosphatase
keywords: bioengineering; biomaterials; carbon; drug delivery; nanomedicine; nanoparticle
references.citation: Spine (Phila Pa 1976). 2010 Sep 1;35(19):1794-800
references.pmid: 20700081
references.citation: Sci Transl Med. 2011 Mar 9;3(73):73ra21
references.pmid: 21389265
references.citation: Clin Oral Implants Res. 2005 Oct;16(5):563-9
references.pmid: 16164462
references.citation: Nanoscale Res Lett. 2010 Apr 14;5(6):1045-50
references.pmid: 20672037
references.citation: J Biomed Mater Res A. 2009 Nov;91(2):548-56
references.pmid: 18985788
references.citation: Talanta. 2010 Jan 15;80(3):1298-304
references.pmid: 20006091
references.citation: Oral Dis. 2006 Jul;12(4):420-3
references.pmid: 16792729
references.citation: Biomaterials. 2009 Oct;30(28):5143-55
references.pmid: 19540582
references.citation: J Mol Biol. 1999 Mar 19;287(1):103-15
references.pmid: 10074410
references.citation: J Orthop Surg Res. 2011 Feb 09;6:8
references.pmid: 21306641
references.citation: Nanoscale. 2011 Jul;3(7):2844-8
references.pmid: 21617824
references.citation: Dev Biol. 1992 Nov;154(1):169-81
references.pmid: 1426624
references.citation: Biomaterials. 2011 Jan;32(1):87-94
references.pmid: 20869765
references.citation: Biomaterials. 2009 Oct;30(29):5720-8
references.pmid: 19635632
references.citation: J Biomed Mater Res B Appl Biomater. 2004 Feb 15;68(2):127-31
references.pmid: 14737759
references.citation: J Biomed Mater Res. 1999 Aug;46(2):193-202
references.pmid: 10379997
references.citation: Adv Mater. 2013 Jul 12;25(26):3532-41
references.pmid: 23584895
references.citation: J Cell Biol. 1994 Dec;127(6 Pt 1):1755-66
references.pmid: 7798324
references.citation: Science. 1988 Dec 16;242(4885):1528-34
references.pmid: 3201241
references.citation: Biomaterials. 2006 Sep;27(26):4547-56
references.pmid: 16725197
references.citation: Anal Chem. 2008 Jun 15;80(12):4659-65
references.pmid: 18476720
references.citation: J Bone Joint Surg Am. 2002 Dec;84(12):2123-34
references.pmid: 12473698
references.citation: ANZ J Surg. 2007 Aug;77(8):626-31
references.pmid: 17635273
references.citation: Biochemistry. 1996 Oct 22;35(42):13552-61
references.pmid: 8885834
references.citation: Arch Oral Biol. 2002 Aug;47(8):577-84
references.pmid: 12221014
references.citation: Development. 1991 Mar;111(3):741-8
references.pmid: 1715258
references.citation: Proc Natl Acad Sci U S A. 1990 Dec;87(24):9843-7
references.pmid: 2263636
references.citation: Bone. 2005 Mar;36(3):399-407
references.pmid: 15777655
references.citation: Bone. 2002 Oct;31(4):465-71
references.pmid: 12398941