Abstract
Introduction
Physical and mechanical properties of ceramic-based scaffolds can be modulated by introducing hydrogel coatings on their surface. For instance, hydrogels can be used as elastic layers to overcome the brittleness of synthetic ceramic materials or to control the delivery of essential osteogenic factors. In this work, we aimed to achieve both goals by fabricating a novel cytocompatible hydrogel made of gelatin-alginate as a coating for beta-tricalcium phosphate (β-TCP) scaffolds.
Methods
The hydrogel synthesis was optimized by varying the concentration of the crosslinkers N-hydroxysuccinimide and N-ethyl-N′-(3-dimethyl aminopropyl) carbodiimide (NHS/EDC). Swelling, degradability and mechanical studies were carried out to identify the suitable hydrogel coating formulation for the β-TCP scaffolds. The cytocompatibility of the coated ceramic was assessed in vitro by testing the proliferation and the osteogenic differentiation of human adipose stem cell (hASCs) for 2 weeks.
Results
The designed hydrogel layer could withstand cyclic compression and protected the brittle internal core of the ceramic. The hydrogel coating modulated the diffusion of the model protein BSA according to the degree of crosslinking of the hydrogel layer. Additionally, the polymeric network was able to retain positively charged proteins such as lysozyme due to the strong electrostatic interactions with carboxylic groups of alginate. A higher expression of alkaline phosphatase activity was found on hASCs seeded on the coated scaffolds compared to the hydrogels without any β-TCP.
Conclusion
Overall, the hydrogel coating characterized in this study represents a valid strategy to overcome limitations of brittle ceramic-based materials used as scaffolds for bone tissue engineering applications.
References
Amini, A. R., C. T. Laurencin, and S. P. Nukavarapu. Bone tissue engineering: recent advances and challenges. Crit. Rev. Biomed. Eng. 40:363–408, 2012.
Arosarena, O. A., F. E. Del Carpio-Cano, R. A. Dela Cadena, M. C. Rico, E. Nwodim, and F. F. Safadi. Comparison of bone morphogenetic protein-2 and osteoactivin for mesenchymal cell differentiation: effects of bolus and continuous administration. J. Cell. Physiol. 226:2943–2952, 2011.
Bose, S., and S. Tarafder. Calcium phosphate ceramic systems in growth factor and drug delivery for bone tissue engineering: a review. Acta Biomater. 8:1401–1421, 2012.
Davidenko, N., C. F. Schuster, D. V. Bax, R. W. Farndale, S. Hamaia, S. M. Best, and R. E. Cameron. Evaluation of cell binding to collagen and gelatin: a study of the effect of 2D and 3D architecture and surface chemistry. J. Mater. Sci. Mater. Med. 27:148, 2016.
Gurkan, U., and O. Akkus. The mechanical environment of bone marrow: a review. Ann. Biomed. Eng. 36:1978–1991, 2008.
Kang, Y. Q., A. Scully, D. A. Young, S. Kim, H. Tsao, M. Sen, and Y. Z. Yang. Enhanced mechanical performance and biological evaluation of a PLGA coated beta-TCP composite scaffold for load-bearing applications. Eur. Polym. J. 47:1569–1577, 2011.
Kuijpers, A. J., G. H. M. Engbers, J. Krijgsveld, S. A. J. Zaat, J. Dankert, and J. Feijen. Cross-linking and characterisation of gelatin matrices for biomedical applications. J. Biomater. Sci. Polym. Ed. 11:225–243, 2000.
Layman, H., M. G. Spiga, T. Brooks, S. Pham, K. A. Webster, and F. M. Andreopoulos. The effect of the controlled release of basic fibroblast growth factor from ionic gelatin-based hydrogels on angiogenesis in a murine critical limb ischemic model. Biomaterials 28:2646–2654, 2007.
Li, Y. B., W. J. Weng, and K. C. Tam. Novel highly biodegradable biphasic tricalcium phosphates composed of alpha-tricalcium phosphate and beta-tricalcium phosphate. Acta Biomater. 3:251–254, 2007.
Liang, G., Y. Z. Yang, S. H. Oh, J. L. Ong, C. Q. Zheng, J. G. Ran, G. F. Yin, and D. L. Zhou. Ectopic osteoinduction and early degradation of recombinant human bone morphogenetic protein-2-loaded porous beta-tricalcium phosphate in mice. Biomaterials 26:4265–4271, 2005.
Lin, K., L. Xia, J. Gan, Z. Zhang, H. Chen, X. Jiang, and J. Chang. Tailoring the nanostructured surfaces of hydroxyapatite bioceramics to promote protein adsorption, osteoblast growth, and osteogenic differentiation. ACS Appl. Mater. Interfaces 5:8008–8017, 2013.
Liu, Y. X., J. H. Kim, D. Young, S. Kim, S. K. Nishimoto, and Y. Z. Yang. Novel template-casting technique for fabricating beta-tricalcium phosphate scaffolds with high interconnectivity and mechanical strength and in vitro cell responses. J. Biomed. Mater. Res. A 92:997–1006, 2010.
Matsushita, N., H. Terai, T. Okada, K. Nozaki, H. Inoue, S. Miyamoto, and K. Takaoka. A new bone-inducing biodegradable porous beta-tricalcium phosphate. J. Biomed. Mater. Res. A 70A:450–458, 2004.
Pacelli, S., S. Basu, J. Whitlow, A. Chakravarti, F. Acosta, A. Varshney, S. Modaresi, C. Berkland, and A. Paul. Strategies to develop endogenous stem cell-recruiting bioactive materials for tissue repair and regeneration. Adv. Drug Deliv. Rev. 120:50–70, 2017.
Pacelli, S., V. Manoharan, A. Desalvo, N. Lomis, K. S. Jodha, S. Prakash, and A. Paul. Tailoring biomaterial surface properties to modulate host-implant interactions: implication in cardiovascular and bone therapy. J. Mater. Chem. B 4(1586):1599, 2016.
Park, I. S., P. S. Chung, and J. C. Ahn. Angiogenic synergistic effect of adipose-derived stromal cell spheroids with low-level light therapy in a model of acute skin flap ischemia. Cells Tissues Organs 202:307–318, 2016.
Reddi, A. H. Bone morphogenetic proteins: from basic science to clinical applications. J. Bone Jt. Surg 83A:S1–S6, 2001.
Samavedi, S., A. R. Whittington, and A. S. Goldstein. Calcium phosphate ceramics in bone tissue engineering: a review of properties and their influence on cell behavior. Acta Biomater. 9:8037–8045, 2013.
Sun, J. Y., X. H. Zhao, W. R. K. Illeperuma, O. Chaudhuri, K. H. Oh, D. J. Mooney, J. J. Vlassak, and Z. G. Suo. Highly stretchable and tough hydrogels. Nature 489:133–136, 2012.
Tarafder, S., K. Nansen, and S. Bose. Lovastatin release from polycaprolactone coated beta-tricalcium phosphate: effects of pH, concentration and drug-polymer interactions. Mater. Sci. Eng. C Mater. Biol. Appl. 33:3121–3128, 2013.
Townsend, J. M., S. C. Dennis, J. Whitlow, Y. Feng, J. Wang, B. Andrews, R. J. Nudo, M. S. Detamore, and C. J. Berkland. Colloidal gels with extracellular matrix particles and growth factors for bone regeneration in critical size rat calvarial defects. AAPS J. 19:703–711, 2017.
Vallet-Regi, M., and A. J. Salinas. Ceramics as Bone Repair Materials. Cambridge: Woodhead Publishing, pp. 194–230, 2009.
Wang, Q., J. Wang, Q. Lu, M. S. Detamore, and C. Berkland. Injectable PLGA based colloidal gels for zero-order dexamethasone release in cranial defects. Biomaterials 31:4980–4986, 2010.
Wang, K., C. Zhou, Y. Hong, and X. Zhang. A review of protein adsorption on bioceramics. Interface Focus 2:259–277, 2012.
Wilson, A., and A. Trumpp. Bone-marrow hematopoietic-stem-cell niches. Nat. Rev. Immunol. 6:93–106, 2006.
Yang, C., H. Frei, F. M. Rossi, and H. M. Burt. The differential in vitro and in vivo responses of bone marrow stromal cells on novel porous gelatin-alginate scaffolds. J. Tissue Eng. Regen. Med. 3:601–614, 2009.
Acknowledgments
A.P. acknowledges an investigator grant provided by the Institutional Development Award (IDeA) from the National Institute of General Medical Sciences (NIGMS) of the NIH Award Number P20GM103638, University of Kansas New Faculty General Research Fund, and Umbilical Cord Matrix Project fund from the State of Kansas (to C.B. and A.P.). J.W. would like to acknowledge the funding support provided by the U.S. National Institute of Health (NIH) under Award Number R01 DE018713.
Conflict of interest
Settimio Pacelli, Sayantani Basu, Cory Berkland, Jinxi Wang and Arghya Paul have no conflicts of interest to disclose.
Ethical Approval
This article does not contain any studies with human participants or animals performed by any of the authors. Only commercially obtained cells were used.
Author information
Authors and Affiliations
Corresponding author
Additional information
Associate Editor Stephanie Michelle Willerth oversaw the review of this article.
Electronic supplementary material
Below is the link to the electronic supplementary material.
Rights and permissions
About this article
Cite this article
Pacelli, S., Basu, S., Berkland, C. et al. Design of a Cytocompatible Hydrogel Coating to Modulate Properties of Ceramic-Based Scaffolds for Bone Repair. Cel. Mol. Bioeng. 11, 211–217 (2018). https://doi.org/10.1007/s12195-018-0521-3
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s12195-018-0521-3