Reinforcement of Mono- and Bi-layer Poly(Ethylene Glycol) Hydrogels with a Fibrous Collagen Scaffold
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Biomaterial-based tissue engineering strategies hold great promise for osteochondral tissue repair. Yet significant challenges remain in joining highly dissimilar materials to achieve a biomimetic, mechanically robust design for repairing interfaces between soft tissue and bone. This study sought to improve interfacial properties and function in a bi-layer hydrogel interpenetrated with a fibrous collagen scaffold. ‘Soft’ 10% (w/w) and ‘stiff’ 30% (w/w) PEGDM was formed into mono- or bi-layer hydrogels possessing a sharp diffusional interface. Hydrogels were evaluated as single-(hydrogel only) or multi-phase (hydrogel + fibrous scaffold penetrating throughout the stiff layer and extending >500 μm into the soft layer). Including a fibrous scaffold into both soft and stiff mono-layer hydrogels significantly increased tangent modulus and toughness and decreased lateral expansion under compressive loading. Finite element simulations predicted substantially reduced stress and strain gradients across the soft—stiff hydrogel interface in multi-phase, bi-layer hydrogels. When combining two low moduli constituent materials, composites theory poorly predicts the observed, large modulus increases. These results suggest material structure associated with the fibrous scaffold penetrating within the PEG hydrogel as the major contributor to improved properties and function—the hydrogel bore compressive loads and the 3D fibrous scaffold was loaded in tension thus resisting lateral expansion.
KeywordsMechanical properties Tissue engineering Osteochondral Interface Hydrogel Scaffold Multi-phase
Research reported in this publication was partially supported by the University of Colorado Innovative Seed Grant Program and NSF CAREER Award CBET #1055989 (K.R.C.K., A.N., M.S., V.L.F.); NSF CAREER Award DMR #0847390 (A.H.A., S.J.B.), NIH R21 AR063331 (L.C.M., B.A.C.H), and a NIH Pharmaceutical Biotechnology Training fellowship to A.H.A. Imaging experiments were performed in the University of Colorado Anschutz Medical Campus Advanced Light Microscopy Core supported in part by NIH/NCATS Colorado CTSI Grant #UL1 TR001082. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH or NSF. The authors also thank Dr. Justine J. Roberts for assistance related to hydrogel synthesis and Rachael C. Paietta for contributions to mechanical testing methods and analysis.
- 7.Caliari, S. R., D. W. Weisgerber, M. A. Ramirez, D. O. Kelkhoff, and B. A. Harley. The influence of collagen-glycosaminoglycan scaffold relative density and microstructural anisotropy on tenocyte bioactivity and transcriptomic stability. J. Mech. Behav. Biomed. Mater. 11:27–40, 2012.PubMedCentralCrossRefPubMedGoogle Scholar
- 9.Caliari, S. R., D. W. Weisgerber, W. K. Grier, Z. Mahmassani, M. D. Boppart, and B. A. Harley. Collagen scaffolds incorporating coincident gradations of instructive structural and biochemical cues for osteotendinous junction engineering. Adv. Healthc. Mater. 4:831–837, 2015.Google Scholar
- 12.Chawla, K. K. Composite Materials Science and Engineering. New York: Springer, 2012.Google Scholar
- 13.Coburn, J., M. Gibson, P. A. Bandalini, C. Laird, H. Q. Mao, L. Moroni, D. Seliktar, and J. Elisseeff. Biomimetics of the extracellular matrix: an integrated three-dimensional fiber-hydrogel composite for cartilage tissue engineering. Smart Struct. Syst. 7:213–222, 2011.PubMedCentralCrossRefPubMedGoogle Scholar
- 17.Farrell, E., F. J. O’Brien, P. Doyle, J. Fischer, I. Yannas, B. A. Harley, B. O’Connell, P. J. Prendergast, and V. A. Campbell. A collagen-glycosaminoglycan scaffold supports adult rat mesenchymal stem cell differentiation along osteogenic and chondrogenic routes. Tissue Eng. 12:459–468, 2006.CrossRefPubMedGoogle Scholar
- 21.Guo, X., J. Liao, H. Park, A. Saraf, R. M. Raphael, Y. Tabata, F. K. Kasper, and A. G. Mikos. Effects of TGF-beta 3 and preculture period of osteogenic cells on the chondrogenic differentiation of rabbit marrow mesenchymal stem cells encapsulated in a bilayered hydrogel composite. Acta Biomater. 6:2920–2931, 2010.PubMedCentralCrossRefPubMedGoogle Scholar
- 24.Harley, B. A., A. K. Lynn, Z. Wissner-Gross, W. Bonfield, I. V. Yannas, and L. J. Gibson. Design of a multiphase osteochondral scaffold III: Fabrication of layered scaffolds with continuous interfaces. J. Biomed. Mater. Res. Part A 92A:1078–1093, 2010.Google Scholar
- 33.Lee, J. C., C. Pereira, X. Ren, W. Huang, D. W. Weisgerber, D. T. Yamaguchi, B. A. Harley, and T. A. Miller. Optimizing collagen scaffolds for bone engineering: effects of crosslinking and mineral content on structural contraction and osteogenesis. J. Craniofac. Sur. 2015. http://journals.lww.com/jcraniofacialsurgery/toc/publishahead.
- 37.Lu, S., J. Lam, J. E. Trachtenberg, E. J. Lee, H. Seyednejad, J. J. den van Beucken, Y. Tabata, M. E. Wong, J. A. Jansen, A. G. Mikos, and F. K. Kasper. Dual growth factor delivery from bilayered, biodegradable hydrogel composites for spatially-guided osteochondral tissue repair. Biomaterials 35:8829–8839, 2014.PubMedCentralCrossRefPubMedGoogle Scholar
- 38.Lynn, A. K., S. M. Best, R. E. Cameron, B. A. Harley, I. V. Yannas, L. J. Gibson, and W. Bonfield. Design of a multiphase osteochondral scaffold. I. Control of chemical composition. J. Biomed. Mater. Res. Part A 92A:1057, 2010.Google Scholar
- 50.Steinmetz, N. J., E. A. Aisenbrey, K. K. Westbrook, H. J. Qi, and S. J. Bryant. Mechanical loading regulates human MSC differentiation in a multi-layer hydrogel for osteochondral tissue engineering. Acta Biomater. 2015. doi: 10.1016/j.actbio.2015.04.015.
- 52.Villanueva, I., D. S. Hauschulz, D. Mejic, and S. J. Bryant. Static and dynamic compressive strains influence nitric oxide production and chondrocyte bioactivity when encapsulated in PEG hydrogels of different crosslinking densities. Osteoarthr. Cartil. 16:909–918, 2008.PubMedCentralCrossRefPubMedGoogle Scholar
- 55.Wang, Y., H. Meng, X. Yuan, J. Peng, Q. Guo, S. Lu, and A. Wang. Fabrication and in vitro evaluation of an articular cartilage extracellular matrix-hydroxyapatite bilayered scaffold with low permeability for interface tissue engineering. Biomed. Eng. Online 13:80, 2014.PubMedCentralCrossRefPubMedGoogle Scholar