TY - JOUR
T1 - Multiscale Porosity Directs Bone Regeneration in Biphasic Calcium Phosphate Scaffolds
AU - Rustom, Laurence E.
AU - Boudou, Thomas
AU - Nemke, Brett W.
AU - Lu, Yan
AU - Hoelzle, David J.
AU - Markel, Mark D.
AU - Picart, Catherine
AU - Wagoner Johnson, Amy J.
N1 - Funding Information:
This work was funded by a grant from the AO Foundation (S-11-17W) and in part by a National Science Foundation grant (CMMI 09-00184). L.E.R. acknowledges the Reǵ ion Rhône-Alpes for International Cooperation and Mobility (CMIRA) and the GIS Mateŕ iaux (Grenoble, France) for travel fellowships. AJWJ acknowledges the support of the Nanosciences Foundation program for Chairs of Excellence (Grenoble, France). C.P. acknowledges the European Commission (FP7) for a European Research Council grant (GA259370). We also acknowledge staff of the Imaging Technology Group at the Beckman Institute for Advanced Science and Technology, part of the University of Illinois at Urbana−Champaign. In particular, we acknowledge L. Yin, S. J. Robinson, C. L. Wallace, and T. Ross for training in the use of micro-CT instruments, scanning electron microscopy, and image processing software, respectively.
Publisher Copyright:
© 2016 American Chemical Society.
PY - 2017/11/13
Y1 - 2017/11/13
N2 - Large and load-bearing bone defects are challenging to treat and cause pain and disfigurement. The design of efficacious bone scaffolds for the repair of such defects involves a range of length scales from the centimeter down to the micrometer-scale. Here, we assess the influence on bone regeneration of scaffold rod spacing (>300 μm) and microporosity (<50 μm), as well as the combination of different structures and materials in the same scaffold, i.e., at the millimeter scale. We use four single-domain scaffolds, microporous (MP) or nonmicroporous (NMP) and with either a "small" or "large" rod spacing. Multidomain scaffolds combine four regions corresponding to the macro- and microarchitectures of the single-domain scaffolds. The scaffolds are implanted in pig mandibles for 3 weeks and bone regeneration is assessed by measuring the average bone volume fraction, BVF, the bone distribution and the trabecular thickness from micro-CT data. For the single-domain scaffolds, BVF was 45 ± 3% for MP-small, 39 ± 2% for MP-large, 25 ± 2% for NMP-small, and 25 ± 2% for NMP-large. MP scaffolds have significantly higher BVF and a more uniform bone distribution compared to NMP, regardless of rod spacing. The average trabecular thickness is significantly larger in MP compared to NMP, and in "large" compared to "small" scaffolds. Microporosity affects trabecular thickness throughout the scaffold, while rod spacing affects it only at the scaffold periphery. In multidomain scaffolds, MP-large and NMP-large domains have similar BVF as compared to their respective single-domain counterparts. These results suggest that combining different architectures into one scaffold conserves the properties of each domain. Hence, bone growth and morphology can be tailored by controlling scaffold architecture from the millimeter down to the micrometer level. This will allow the customization of scaffold designs for the treatment of large and load-bearing bone defects.
AB - Large and load-bearing bone defects are challenging to treat and cause pain and disfigurement. The design of efficacious bone scaffolds for the repair of such defects involves a range of length scales from the centimeter down to the micrometer-scale. Here, we assess the influence on bone regeneration of scaffold rod spacing (>300 μm) and microporosity (<50 μm), as well as the combination of different structures and materials in the same scaffold, i.e., at the millimeter scale. We use four single-domain scaffolds, microporous (MP) or nonmicroporous (NMP) and with either a "small" or "large" rod spacing. Multidomain scaffolds combine four regions corresponding to the macro- and microarchitectures of the single-domain scaffolds. The scaffolds are implanted in pig mandibles for 3 weeks and bone regeneration is assessed by measuring the average bone volume fraction, BVF, the bone distribution and the trabecular thickness from micro-CT data. For the single-domain scaffolds, BVF was 45 ± 3% for MP-small, 39 ± 2% for MP-large, 25 ± 2% for NMP-small, and 25 ± 2% for NMP-large. MP scaffolds have significantly higher BVF and a more uniform bone distribution compared to NMP, regardless of rod spacing. The average trabecular thickness is significantly larger in MP compared to NMP, and in "large" compared to "small" scaffolds. Microporosity affects trabecular thickness throughout the scaffold, while rod spacing affects it only at the scaffold periphery. In multidomain scaffolds, MP-large and NMP-large domains have similar BVF as compared to their respective single-domain counterparts. These results suggest that combining different architectures into one scaffold conserves the properties of each domain. Hence, bone growth and morphology can be tailored by controlling scaffold architecture from the millimeter down to the micrometer level. This will allow the customization of scaffold designs for the treatment of large and load-bearing bone defects.
KW - bone scaffold
KW - calcium phosphate
KW - micro-CT
KW - multiscale porosity
KW - scaffold patterning
KW - trabecular morphology
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U2 - 10.1021/acsbiomaterials.6b00632
DO - 10.1021/acsbiomaterials.6b00632
M3 - Article
AN - SCOPUS:85034019286
SN - 2373-9878
VL - 3
SP - 2768
EP - 2778
JO - ACS Biomaterial Science and Engineering
JF - ACS Biomaterial Science and Engineering
IS - 11
ER -