title: A mechanism for effective cell-seeding in rigid, microporous substrates.
abstract: Seeding cells into porous ceramic substrates has been shown to improve outcomes in surgical repair of large bone defects, but the physics underlying cellular ingress into such scaffolds remains elusive. This paper demonstrates capillary forces as a novel, yet simple, self-loading or self-seeding mechanism for rigid, microporous substrates. Capillary forces were found to draw cells through a microporous network with interconnections smaller than the diameter of the cells in suspension. Work here emphasizes CaP-based bone scaffolds containing both macroporosity (>100μm) and microporosity (5-50μm); these have been shown to improve bone formation in vivo as compared to their macroporous counterparts and also performed better than microporous scaffolds containing BMP-2 by some measures of bone regeneration. We hypothesize that capillary force driven self-seeding in both macro- and micropores may underlie this improvement, and present a mathematical model and experiments that support this hypothesis. The cell localization and penetration depth within these two-dimensional substrates in vitro depends upon both the cell type (size and stiffness) and the capillary forces generated by the microstructure. Additional experiments showing that cell penetration depth in vitro depends on cell size and stiffness suggest that microporosity could be tailored to optimize cell infiltration in a cell-specific way. Endogenous cells are also drawn into the microporous network in vivo. Results have important implications for design of scaffolds for the healing of large bone defects, and for controlled release of drugs in vivo.
authors.affiliation: Department of Bioengineering, University of Illinois at Urbana-Champaign, 1304 West Springfield Avenue, Urbana, IL 61801, USA. spolak2@illinois.edu
authors.forename: S J
authors.initials: SJ
authors.lastname: Polak
authors.forename: L E
authors.initials: LE
authors.lastname: Rustom
authors.forename: G M
authors.initials: GM
authors.lastname: Genin
authors.forename: M
authors.initials: M
authors.lastname: Talcott
authors.forename: A J
authors.initials: AJ
authors.lastname: Wagoner Johnson
mesh_terms: D000818:Animals; D018786:Bone Substitutes / Q000138:chemical synthesis*; D002130:Calcium Phosphates / Q000737:chemistry*; D002197:Capillary Action; D002448:Cell Adhesion / Q000502:physiology; D002460:Cell Line; D049109:Cell Proliferation; D055119:Elastic Modulus; D004867:Equipment Design; D019544:Equipment Failure Analysis; D008297:Male; D008337:Mandibular Fractures / Q000473:pathology / Q000601:surgery*; D008422:Materials Testing; D008904:Miniaturization; D010006:Osteoblasts / Q000166:cytology* / Q000502:physiology / Q000637:transplantation*; D016062:Porosity; D013499:Surface Properties; D013552:Swine; D023822:Tissue Engineering / Q000295:instrumentation*; D054457:Tissue Scaffolds; D016896:Treatment Outcome
chemical_list: D018786:Bone Substitutes; D002130:Calcium Phosphates; C020243:calcium phosphate