title: Silk implants for the healing of critical size bone defects.
abstract: Bone (re)-generation and bone fixation strategies utilize biomaterial implants, which are gradually replaced by autologous tissues. Ideally, these biomaterials should be biodegradable, osteoconductive, and provide mechanical strength and integrity until newly formed host tissues can maintain function. Some protein-based biomaterials such as collagens are promising because of their biological similarities to natural proteins on bone surfaces. However, their use as bone implant materials is largely hampered by poor mechanical properties. In contrast, silks offer distinguishing mechanical properties that are tailorable, along with slow degradability to permit adequate time for remodeling. To assess the suitability of silk-based biomaterials as implants for bone healing, we explored the use of novel porous silk fibroin scaffolds as templates for the engineering of bone tissues starting from human bone marrow derived stem cells cultured under osteogenic conditions for up to 5 weeks. The slowly degrading protein matrix permitted adequate temporal control of hydroxyapatite deposition and resulted in the formation of a trabecular-like bone matrix in bioreactor studies. The organic and inorganic components of the engineered bone tissues resembled those of bone, as shown by gene expression analysis, biochemical assays, and X-ray diffractometry. Implantation of the tissue-engineered bone implants (grown in bioreactors for 5 weeks prior to implantation) into calvarial critical size defects in mice demonstrated the capacity of these systems to induce advanced bone formation within 5 weeks, whereas the implantation of stem cell loaded silk scaffolds, and scaffolds alone resulted in less bone formation. These results demonstrate the feasibility of silk-based implants with engineered bone for the (re-)generation of bone tissues and expand the class of protein-based bone-implant materials with a mechanically stable and durable option.
authors.affiliation: Department of Biomedical Engineering, Tufts University, 4 Colby Street, Medford, MA 02155, USA.
authors.forename: Lorenz
authors.initials: L
authors.lastname: Meinel
authors.forename: Robert
authors.initials: R
authors.lastname: Fajardo
authors.forename: Sandra
authors.initials: S
authors.lastname: Hofmann
authors.forename: Robert
authors.initials: R
authors.lastname: Langer
authors.forename: Jake
authors.initials: J
authors.lastname: Chen
authors.forename: Brian
authors.initials: B
authors.lastname: Snyder
authors.forename: Gordana
authors.initials: G
authors.lastname: Vunjak-Novakovic
authors.forename: David
authors.initials: D
authors.lastname: Kaplan
mesh_terms: D000818:Animals; D001672:Biocompatible Materials; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins / Q000096:biosynthesis / Q000235:genetics; D050659:Core Binding Factor Alpha 1 Subunit / Q000096:biosynthesis / Q000235:genetics; D005349:Fibroins; D017102:Fracture Healing / Q000235:genetics / Q000502:physiology*; D006801:Humans; D007150:Immunohistochemistry; D058574:Integrin-Binding Sialoprotein; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism / Q000502:physiology; D051379:Mice; D008819:Mice, Nude; D010012:Osteogenesis / Q000235:genetics; D053495:Osteopontin; D019736:Prostheses and Implants; D012795:Sialoglycoproteins / Q000096:biosynthesis / Q000235:genetics; D012886:Skull / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D012887:Skull Fractures; D023822:Tissue Engineering; D014158:Transcription, Genetic; D016212:Transforming Growth Factor beta / Q000096:biosynthesis / Q000235:genetics; D014961:X-Ray Diffraction
chemical_list: C525718:BMP2 protein, human; D001672:Biocompatible Materials; C525719:Bmp2 protein, mouse; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins; D050659:Core Binding Factor Alpha 1 Subunit; C546871:IBSP protein, human; C546872:Ibsp protein, mouse; D058574:Integrin-Binding Sialoprotein; C506895:SPP1 protein, human; D012795:Sialoglycoproteins; C506896:Spp1 protein, mouse; D016212:Transforming Growth Factor beta; C482288:fibroin, silkworm; D053495:Osteopontin; D005349:Fibroins