title: Micropore-induced capillarity enhances bone distribution in vivo in biphasic calcium phosphate scaffolds.
abstract: The increasing demand for bone repair solutions calls for the development of efficacious bone scaffolds. Biphasic calcium phosphate (BCP) scaffolds with both macropores and micropores (MP) have improved healing compared to those with macropores and no micropores (NMP), but the role of micropores is unclear. Here, we evaluate capillarity induced by micropores as a mechanism that can affect bone growth in vivo. Three groups of cylindrical scaffolds were implanted in pig mandibles for three weeks: MP were implanted either dry (MP-Dry), or after submersion in phosphate buffered saline, which fills pores with fluid and therefore suppresses micropore-induced capillarity (MP-Wet); NMP were implanted dry. The amount and distribution of bone in the scaffolds were quantified using micro-computed tomography. MP-Dry had a more homogeneous bone distribution than MP-Wet, although the average bone volume fraction, BVF‾, was not significantly different for these two groups (0.45±0.03 and 0.37±0.03, respectively). There was no significant difference in the radial bone distribution of NMP and MP-Wet, but the BVF‾, of NMP was significantly lower among the three groups (0.25±0.02). These results suggest that micropore-induced capillarity enhances bone regeneration by improving the homogeneity of bone distribution in BCP scaffolds. The explicit design and use of capillarity in bone scaffolds may lead to more effective treatments of large and complex bone defects.
  
  
  
  The increasing demand for bone repair calls for more efficacious bone scaffolds and calcium phosphate-based materials are considered suitable for this application. Macropores (>100μm) are necessary for bone ingrowth and vascularization. However, studies have shown that microporosity (<20μm) also enhances growth, but there is no consensus on the controlling mechanisms. In previous in vitro work, we suggested that micropore-induced capillarity had the potential to enhance bone growth in vivo. This work illustrates the positive effects of capillarity on bone regeneration in vivo; it demonstrates that micropore-induced capillarity significantly enhances the bone distribution in the scaffold. The results will impact the design of scaffolds to better exploit capillarity and improve treatments for large and load-bearing bone defects.
authors.affiliation: Department of Bioengineering, University of Illinois at Urbana-Champaign, 1270 Digital Computer Laboratory, MC-278, 1304 West Springfield Avenue, Urbana, IL 61801, USA; University Grenoble Alpes, LMGP, 38000 Grenoble, France. Electronic address: rustom2@illinois.edu.
authors.forename: Laurence E
authors.initials: LE
authors.lastname: Rustom
authors.affiliation: University Grenoble Alpes, LMGP, 38000 Grenoble, France; CNRS UMR 5628 (LMGP), 3 parvis Louis Néel, 38016 Grenoble, France. Electronic address: thomas.boudou@grenoble-inp.fr.
authors.forename: Thomas
authors.initials: T
authors.lastname: Boudou
authors.affiliation: University Grenoble Alpes, LMGP, 38000 Grenoble, France; CNRS UMR 5628 (LMGP), 3 parvis Louis Néel, 38016 Grenoble, France; School of Materials Science and Engineering, Shanghai Jiao Tong University, 800 Dongchuan Road, 200240 Shanghai, China. Electronic address: lousiyushanghai@gmail.com.
authors.forename: Siyu
authors.initials: S
authors.lastname: Lou
authors.affiliation: University Grenoble Alpes, LMGP, 38000 Grenoble, France; CNRS UMR 5628 (LMGP), 3 parvis Louis Néel, 38016 Grenoble, France. Electronic address: isabelle.paintrand@grenoble-inp.fr.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Pignot-Paintrand
authors.affiliation: School of Veterinary Medicine, University of Wisconsin - Madison, 2015 Linden Drive, Madison, WI 53706, USA. Electronic address: brett.nemke@wisc.edu.
authors.forename: Brett W
authors.initials: BW
authors.lastname: Nemke
authors.affiliation: School of Veterinary Medicine, University of Wisconsin - Madison, 2015 Linden Drive, Madison, WI 53706, USA. Electronic address: yan.lu@wisc.edu.
authors.forename: Yan
authors.initials: Y
authors.lastname: Lu
authors.affiliation: School of Veterinary Medicine, University of Wisconsin - Madison, 2015 Linden Drive, Madison, WI 53706, USA. Electronic address: mark.markel@wisc.edu.
authors.forename: Mark D
authors.initials: MD
authors.lastname: Markel
authors.affiliation: University Grenoble Alpes, LMGP, 38000 Grenoble, France; CNRS UMR 5628 (LMGP), 3 parvis Louis Néel, 38016 Grenoble, France. Electronic address: catherine.picart@grenoble-inp.fr.
authors.forename: Catherine
authors.initials: C
authors.lastname: Picart
authors.affiliation: Department of Bioengineering, University of Illinois at Urbana-Champaign, 1270 Digital Computer Laboratory, MC-278, 1304 West Springfield Avenue, Urbana, IL 61801, USA; University Grenoble Alpes, LMGP, 38000 Grenoble, France; Department of Mechanical Science and Engineering, University of Illinois at Urbana-Champaign, 1206 West Green Street, Urbana, IL 61801, USA. Electronic address: ajwj@illinois.edu.
authors.forename: Amy J
authors.initials: AJ
authors.lastname: Wagoner Johnson
mesh_terms: D000818:Animals; D001861:Bone Regeneration / Q000187:drug effects; D001842:Bone and Bones / Q000098:blood supply / Q000000981:diagnostic imaging / Q000187:drug effects*; D002130:Calcium Phosphates / Q000494:pharmacology*; D002197:Capillary Action; D009929:Organ Size; D016062:Porosity; D034421:Sus scrofa; D054457:Tissue Scaffolds / Q000737:chemistry*; D055114:X-Ray Microtomography
chemical_list: D002130:Calcium Phosphates; C020243:calcium phosphate
keywords: Bone regeneration; Calcium phosphate scaffold; Capillary action; Micro-computed tomography; Microporosity