Effect of polycaprolactone scaffold permeability on bone regeneration in vivo - PubMed (original) (raw)

Effect of polycaprolactone scaffold permeability on bone regeneration in vivo

Anna G Mitsak et al. Tissue Eng Part A. 2011 Jul.

Abstract

Successful bone tissue engineering depends on the scaffold's ability to allow nutrient diffusion to and waste removal from the regeneration site, as well as provide an appropriate mechanical environment. Since bone is highly vascularized, scaffolds that provide greater mass transport may support increased bone regeneration. Permeability encompasses the salient features of three-dimensional porous scaffold architecture effects on scaffold mass transport. We hypothesized that higher permeability scaffolds will enhance bone regeneration for a given cell seeding density. We manufactured poly-ɛ-caprolactone scaffolds, designed to have the same internal pore design and either a low permeability (0.688×10(-7)m(4)/N-s) or a high permeability (3.991×10(-7)m(4)/N-s), respectively. Scaffolds were seeded with bone morphogenic protein-7-transduced human gingival fibroblasts and implanted subcutaneously in immune-compromised mice for 4 and 8 weeks. Micro-CT evaluation showed better bone penetration into high permeability scaffolds, with blood vessel infiltration visible at 4 weeks. Compression testing showed that scaffold design had more influence on elastic modulus than time point did and that bone tissue infiltration increased the mechanical properties of the high permeability scaffolds at 8 weeks. These results suggest that for polycaprolactone, a more permeable scaffold with regular architecture is best for in vivo bone regeneration. This finding is an important step toward the end goal of optimizing a scaffold for bone tissue engineering.

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Figures

FIG. 1.

FIG. 1.

(a) Bone volume (BV) inside the scaffold ROI at 4 and 8 weeks. (b) Bone in-growth for the entire scaffold ROI at 4 and 8 weeks. *_p_≤0.05. **_p_≤0.01. ROI, region of interest. Color images available online at

www.liebertonline.com/tea

FIG. 2.

FIG. 2.

Micro-CT image slices from the center of representative low and high permeability scaffolds. (a) Low permeability scaffold at 4 weeks, (b) low permeability scaffold at 8 weeks, (c) high permeability scaffold at 4 weeks, and (d) high permeability scaffold at 8 weeks. Color images available online at

www.liebertonline.com/tea

FIG. 3.

FIG. 3.

(a) Tissue mineral content (TMC) and (b) tissue mineral density (TMD) at 4 and 8 weeks. *_p_≤0.05. Color images available online at

www.liebertonline.com/tea

FIG. 4.

FIG. 4.

Micro-CT slice images showing top-down views of the cylindrical ROIs used for the concentric BV analysis. (a–d) show the four concentric ROIs, each with a progressively smaller outer diameter, and (e) shows all four ROIs overlaid on one another. Color images available online at

www.liebertonline.com/tea

FIG. 5.

FIG. 5.

Concentric cylinder BV analysis. (a) BV and (b) bone in-growth for high and low permeability scaffolds and 4 and 8 weeks, for four hollow, cylindrical ROIs. **_p_≤0.01. Color images available online at

www.liebertonline.com/tea

FIG. 6.

FIG. 6.

(a) Tangent modulus at 12.5% strain, 4 and 8 weeks. (b) Compressive yield strength at 0.2% offset. *_p_≤0.05. **_p_≤0.01. Color images available online at

www.liebertonline.com/tea

FIG. 7.

FIG. 7.

Representative histological sections of high permeability (a, b) and low permeability (c, d) scaffolds at 8 weeks. (b) and (d) are higher magnification images of rectangular insets indicated in (a) and (c). The scaffold is indicated by “S” and bone growth in and around the scaffold is indicated by the dark pink staining and arrows. Osteocytes in lacunae are seen in both high and low permeability scaffolds (indicated by dashed circles) as is marrow space (“M”). Blood vessels are also seen in the high permeability scaffold (BV). Color images available online at

www.liebertonline.com/tea

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References

    1. Karande T.S. Ong J.L. Agrawal C.M. Diffusion in musculoskeletal tissue engineering scaffolds: design issues related to porosity, permeability, and nutrient mixing. Ann Biomed Eng. 2004;32:1728. - PubMed
    1. Jones A.C. Arns C.H. Hutmacher D.W. Milthorpe B.K. Sheppard A.P. Knackstedt M.A. The correlation of pore morphology, interconnectivity and physical properties of 3D ceramic scaffolds with bone ingrowth. Biomaterials. 2009;30:1440. - PubMed
    1. Lee K.E. Wang S. Fox B.C. Ritman E.L. Yaszemski M.J. Lu L. Poly(propylene fumurate) bone tissue engineering scaffold fabrication using stereolithography: effects of resin formulations and laser parameters. Biomacromolecules. 2007;8:1077. - PubMed
    1. Wang K. Cai L. Hao F. Xu X. Cui M. Wang S. Distinct cell responses to substrates consisting of poly-ɛ-caprolactone and poly(propylene fumurate) in the presence or absence of cross-links. Biomacromolecules. 2010;11:2748. - PubMed
    1. Ciapetti G. Ambrosio L. Savarino L. Granchi D. Cenni E. Baldini N., et al. Osteoblast growth and function in porous poly-ɛ-caprolactone matrices for bone repair: a preliminary study. Biomaterials. 2003;24:3815. - PubMed

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