Abstract
Cell-material and cell-cell interactions represent two crucial aspects of the regulation of cell behavior. In the present study, poly (L-glutamic acid) (PLG) hydrogels were prepared by catalyst-free click crosslinking via a strain-promoted azide-alkyne cycloaddition (SPAAC) reaction between azido-grafted PLG (PLG-N3) and azadibenzocyclooctyne-grafted PLG (PLG-ADIBO). The bioactive peptides c(RGDfK) and N-cadherin mimetic peptide (N-Cad) were both conjugated to the PLG hydrogel (denoted PLG+RGD/N-Cad) in order to regulate cell-material and cell-cell interactions. Gelation time and storage modulus of the hydrogels were tunable through variations in the concentration of polypeptide precursors. The hydrogels degraded gradually in the presence of proteinases. The viability of bone marrow mesenchymal stem cells (BMSCs) was maintained when cultured with extracts of the hydrogels or encapsulated within the hydrogels. Degradation was observed within 10 weeks following the subcutaneous injection of hydrogel solution in rats, displaying excellent histocompatibility in vivo. The introduction of RGD into the PLG hydrogel promoted the adhesion of BMSCs onto the hydrogels. Moreover, when encapsulated within the PLG+RGD/N-Cad hydrogel, BMSCs secreted cartilage-specific matrix, in addition to chondrogenic gene and protein expression being significantly enhanced in comparison with BMSCs encapsulated in hydrogels without N-Cad modification. These findings suggest that these biodegradable, bioactive polypeptide hydrogels have great potential for use in 3D cell culture and in cartilage tissue engineering.
Article PDF
Similar content being viewed by others
Explore related subjects
Discover the latest articles, news and stories from top researchers in related subjects.Avoid common mistakes on your manuscript.
References
Langer R. Mol Ther, 2000, 1: 12–15
Lee KY, Mooney DJ. Chem Rev, 2001, 101: 1869–1880
Moon HJ, Ko DY, Park MH, Joo MK, Jeong B. Chem Soc Rev, 2012, 41: 4860
Tsou YH, Khoneisser J, Huang PC, Xu X. Bioactive Mater, 2016, 1: 39–55
Zhong L, Qu Y, Shi K, Chu B, Lei M, Huang K, Gu Y, Qian Z. Sci China Chem, 2018, 61: 1553–1567
Yu L, Ding J. Chem Soc Rev, 2008, 37: 1473
Rice JJ, Martino MM, De Laporte L, Tortelli F, Briquez PS, Hubbell JA. Adv Healthc Mater, 2013, 2: 57–71
Annabi N, Tamayol A, Uquillas JA, Akbari M, Bertassoni LE, Cha C, Camci-Unal G, Dokmeci MR, Peppas NA, Khademhosseini A. Adv Mater, 2015, 26: 85–124
Xue K, Wang X, Yong PW, Young DJ, Wu YL, Li Z, Loh XJ. Adv Therap, 2019, 2: 1800088
Lv J, Wu G, Liu Y, Li C, Huang F, Zhang Y, Liu J, An Y, Ma R, Shi L. Sci China Chem, 2019, 62: 637–648
Deming TJ. Prog Polym Sci, 2007, 32: 858–875
He C, Zhuang X, Tang Z, Tian H, Chen X. Adv Healthc Mater, 2012, 1: 48–78
Shirbin SJ, Karimi F, Chan NJA, Heath DE, Qiao GG. Biomacromolecules, 2016, 17: 2981–2991
Hu C, Liu X, Ran W, Meng J, Zhai Y, Zhang P, Yin Q, Yu H, Zhang Z, Li Y. Biomaterials, 2017, 144: 60–72
Ren K, He C, Xiao C, Li G, Chen X. Biomaterials, 2015, 51: 238–249
Ren K, Cui H, Xu Q, He C, Li G, Chen X. Biomacromolecules, 2016, 17: 3862–3871
Xu Q, He C, Zhang Z, Ren K, Chen X. ACS Appl Mater Interfaces, 2016, 8: 30692–30702
Zhou X, Li Z. Adv Healthc Mater, 2018, 7: 1800020
Patel M, Park S, Lee HJ, Jeong B. Tissue Eng Regen Med, 2018, 15: 521–530
Liu R, Shi Z, Sun J, Li Z. Sci China Chem, 2018, 61: 1414–1319
Yan S, Zhang X, Zhang K, Di H, Feng L, Li G, Fang J, Cui L, Chen X, Yin J. J Mater Chem B, 2016, 4: 947–961
Agard NJ, Prescher JA, Bertozzi CR. J Am Chem Soc, 2004, 126: 15046–15047
Kim E, Koo H. Chem Sci, 2019, 10: 7835–7851
Madl CM, Katz LM, Heilshorn SC. Adv Funct Mater, 2016, 26: 3612–3620
Xu J, Filion TM, Prifti F, Song J. Chem Asian J, 2011, 6: 2730–2737
DeForest CA, Anseth KS. Annu Rev Chem Biomol Eng, 2012, 3: 421–444
Tibbitt MW, Rodell CB, Burdick JA, Anseth KS. Proc Natl Acad Sci USA, 2015, 112: 14444–14451
Shi S, Yu SJ, Li G, He CL, Chen XS. Sci China Technol Sci, 2020, https://doi.org/10.1007/s11431-019-1466-1
Hersel U, Dahmen C, Kessler H. Biomaterials, 2003, 24: 4385–4415
Leahy DJ, Aukhil I, Erickson HP. Cell, 1996, 84: 155–164
Yao X, Peng R, Ding J. Adv Mater, 2013, 25: 5257–5286
DeLise AM, Tuan RS. J Cell Biochem, 2002, 87: 342–359
Delise AM, Tuan RS. Dev Dyn, 2002, 225: 195–204
Gumbiner BM. Nat Rev Mol Cell Biol, 2005, 6: 622–634
Blaschuk OW, Sullivan R, David S, Pouliot Y. Dev Biol, 1990, 139: 227–229
Williams E, Williams G, Gour BJ, Blaschuk OW, Doherty P. J Biol Chem, 2000, 275: 4007–4012
Li R, Xu J, Wong DSH, Li J, Zhao P, Bian L. Biomaterials, 2017, 145: 33–43
Bian L, Guvendiren M, Mauck RL, Burdick JA. Proc Natl Acad Sci USA, 2013, 110: 10117–10122
Cosgrove BD, Mui KL, Driscoll TP, Caliari SR, Mehta KD, Assoian RK, Burdick JA, Mauck RL. Nat Mater, 2016, 15: 1297–1306
Kwon MY, Vega SL, Gramlich WM, Kim M, Mauck RL, Burdick JA. Adv Healthc Mater, 2018, 7: 1701199
Zhao C, Zhuang X, He C, Chen X, Jing X. Macromol Rapid Commun, 2008, 29: 1810–1816
Cheng Y, He C, Xiao C, Ding J, Zhuang X, Chen X. Polym Chem, 2011, 2: 2627
Graf N, Bielenberg DR, Kolishetti N, Muus C, Banyard J, Farokhzad OC, Lippard SJ. ACS Nano, 2012, 6: 4530–4539
Mann T, Leone E. Biochem J, 1953, 53: 140–148
Chung C, Anderson E, Pera RR, Pruitt BL, Heilshorn SC. Soft Matter, 2012, 8: 10141
Bian L, Hou C, Tous E, Rai R, Mauck RL, Burdick JA. Biomaterials, 2013, 34: 413–421
M. Jonker A, A. Bode S, H. Kusters A, van Hest JCM, Löwik DWPM. Macromol Biosci, 2015, 15: 1338–1347
Even-Ram S, Artym V, Yamada KM. Cell, 2006, 126: 645–647
Sridhar BV, Brock JL, Silver JS, Leight JL, Randolph MA, Anseth KS. Adv Healthc Mater, 2015, 4: 702–713
Ren K, He C, Cheng Y, Li G, Chen X. Polym Chem, 2014, 5: 5069–5076
Park H, Choi B, Hu J, Lee M. Acta Biomater, 2013, 9: 4779–4786
Qu C, Bao Z, Zhang X, Wang Z, Ren J, Zhou Z, Tian M, Cheng X, Chen X, Feng C. Int J Biol Macromolecules, 2019, 125: 78–86
Lueckgen A, Garske DS, Ellinghaus A, Mooney DJ, Duda GN, Cipitria A. Biomaterials, 2019, 217: 119294
Ansari S, Chen C, Xu X, Annabi N, Zadeh HH, Wu BM, Khademhosseini A, Shi S, Moshaverinia A. Ann Biomed Eng, 2016, 44: 1908–1920
Hong KH, Song SC. Biomaterials, 2019, 218: 119338
Yang J, Zhang YS, Yue K, Khademhosseini A. Acta Biomater, 2017, 57: 1–25
Acknowledgements
This work was supported by the National Natural Science Foundation of China (51973218, 51622307, 21574127, 51520105004) and the Youth Innovation Promotion Association, Chinese Academy of Sciences.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interest The authors declare no conflict of interest.
Supporting Information
11426_2020_9772_MOESM1_ESM.docx
Bioactive polypeptide hydrogels modified with RGD and N-cadherin mimetic peptide promote chondrogenic differentiation of bone marrow mesenchymal stem cells
Rights and permissions
About this article
Cite this article
Rong, Y., Zhang, Z., He, C. et al. Bioactive polypeptide hydrogels modified with RGD and N-cadherin mimetic peptide promote chondrogenic differentiation of bone marrow mesenchymal stem cells. Sci. China Chem. 63, 1100–1111 (2020). https://doi.org/10.1007/s11426-020-9772-0
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11426-020-9772-0