Enhanced Proliferation of Human Mesenchymal Stem Cells by Self-Assembled Peptide Hydrogel Modified with Heparin Mimetic Peptide
Year 2022,
Issue: 41, 59 - 66, 30.11.2022
Gülşah Sunal
,
Günnur Onak Pulat
,
Ozan Karaman
Abstract
The development of three-dimensional (3D) microenvironments that mimic the role of native extracellular matrix (ECM) components is very crucial. Self-assembling peptide (SAP) hydrogels have been utilized as scaffolds for encapsulation, 3D culture, proliferation, and differentiation of cells and also for repairing defects in cartilage tissue. SAPs can be biofunctionalized with short peptide epitopes to form biomimetic scaffolds. Herein, KLD (KLDLKLDLKLDL) SAP was functionalized with a short bioactive motif, EGDK, to fabricate KLD-HM (KLDLKLDLKLDL-EGDK) SAP hydrogel and self-assembled. In this study, it was aimed to investigate the effect of developed KLD-HM SAP hydrogels on the viability and proliferation of human mesenchymal stem cells (hMSCs). For ensuring the stability of SAPs, the rheological properties and degradation profile of produced SAP hydrogels were assessed. After the encapsulation of hMSCs in SAP hydrogels, MTT assay and Live and Dead staining assay were conducted. We showed that these biomimetic peptide hydrogel scaffolds provided a proper microenvironment for encapsulated hMSCs and the developed SAP hydrogels promoted the adhesion, viability, and proliferation of hMSCs. Our results suggest that designed bioactive SAP hydrogel scaffolds might be useful for promoting the regeneration of cartilage tissue.
Project Number
Authors acknowledge funding from TÜBİTAK (The Scientific and Technological Research Council of Turkey) in the scope of 2209-A University Students Research Projects Support Program and TÜBİTAK 1002 Program (Project No:121S133).
Thanks
Authors acknowledge funding from TÜBİTAK (The Scientific and Technological Research Council of Turkey) in the scope of 2209-A University Students Research Projects Support Program and TÜBİTAK 1002 Program (Project No:121S133).
References
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- Arslan, E., Üstün Yaylacı, S., Güler, M. O., & Tekinay, A. B. (2016). Therapeutic nanomaterials for cartilage regeneration. In Therapeutic nanomaterials (pp. 59-85): Wiley Online Library.
- Barati, D., Moeinzadeh, S., Karaman, O., & Jabbari, E. (2014). Time dependence of material properties of polyethylene glycol hydrogels chain extended with short hydroxy acid segments. Polymer (Guildf), 55(16), 3894-3904.
- Carballo, C. B., Nakagawa, Y., Sekiya, I., & Rodeo, S. A. (2017). Basic science of articular cartilage. Clinics in sports medicine, 36(3), 413-425.
- Chung, C., & Burdick, J. A. (2008). Engineering cartilage tissue. Advanced drug delivery reviews, 60(2), 243-262.
- Dikecoglu, F. B., Topal, A. E., Ozkan, A. D., Tekin, E. D., Tekinay, A. B., Guler, M. O., & Dana, A. (2018). Force and time-dependent self-assembly, disruption and recovery of supramolecular peptide amphiphile nanofibers. Nanotechnology, 29(28), 285701.
- Eren Cimenci, C., Kurtulus, G. U., Caliskan, O. S., Guler, M. O., & Tekinay, A. B. (2019). N-cadherin mimetic peptide nanofiber system induces chondrogenic differentiation of mesenchymal stem cells. Bioconjugate chemistry, 30(9), 2417-2426.
- Jackson, R. L., Busch, S. J., & Cardin, A. D. (1991). Glycosaminoglycans: molecular properties, protein interactions, and role in physiological processes. Physiological reviews, 71(2), 481-539.
- Karaman, K., Kumar, A., He, X., & Jabbari, E. (2012). Glutamic acid grafted nanofibers as a biomimetic template for mineralization and osteogenic differentiation of mesenchymal stem cells. Paper presented at the Journal of tissue engineering and regenerative medicine.
- Karaman, O., Kumar, A., Moeinzadeh, S., He, X., Cui, T., & Jabbari, E. (2016). Effect of surface modification of nanofibres with glutamic acid peptide on calcium phosphate nucleation and osteogenic differentiation of marrow stromal cells. Journal of tissue engineering and regenerative medicine, 10(2), E132-E146.
- Kisiday, J., Jin, M., Kurz, B., Hung, H., Semino, C., Zhang, S., & Grodzinsky, A. (2002). Self-assembling peptide hydrogel fosters chondrocyte extracellular matrix production and cell division: implications for cartilage tissue repair. Proceedings of the National Academy of Sciences, 99(15), 9996-10001.
- Kocabey, S., Ceylan, H., Tekinay, A. B., & Guler, M. O. (2013). Glycosaminoglycan mimetic peptide nanofibers promote mineralization by osteogenic cells. Acta biomaterialia, 9(11), 9075-9085.
- Koch, F., Müller, M., König, F., Meyer, N., Gattlen, J., Pieles, U., . . . Saxer, S. (2018). Mechanical characteristics of beta sheet-forming peptide hydrogels are dependent on peptide sequence, concentration and buffer composition. Royal Society open science, 5(3), 171562-171562. doi:10.1098/rsos.171562
- Kokubo, T., & Takadama, H. (2006). Leading Opinion. How useful is SBF in predicting in vivo bone bioactivity, Biomaterial, 27, 2907-2915.
- Li, R., Xu, J., Wong, D. S. H., Li, J., Zhao, P., & Bian, L. (2017). Self-assembled N-cadherin mimetic peptide hydrogels promote the chondrogenesis of mesenchymal stem cells through inhibition of canonical Wnt/β-catenin signaling. Biomaterials, 145, 33-43.
- Lim, E.-H., Sardinha, J. P., & Myers, S. (2014). Nanotechnology biomimetic cartilage regenerative scaffolds. Archives of plastic surgery, 41(3), 231.
- Liu, M., Zeng, X., Ma, C., Yi, H., Ali, Z., Mou, X., . . . He, N. (2017). Injectable hydrogels for cartilage and bone tissue engineering. Bone research, 5(1), 1-20.
- Liu, S. Q., Tian, Q., Hedrick, J. L., Hui, J. H. P., Ee, P. L. R., & Yang, Y. Y. (2010). Biomimetic hydrogels for chondrogenic differentiation of human mesenchymal stem cells to neocartilage. Biomaterials, 31(28), 7298-7307.
- Lu, J., & Wang, X. (2018). Biomimetic self-assembling peptide hydrogels for tissue engineering applications. Biomimetic Medical Materials, 297-312.
- Lum, L., & Elisseeff, J. (2003). Injectable hydrogels for cartilage tissue engineering. Topics in tissue engineering, 1.
Mammadov, R., Mammadov, B., Guler, M. O., & Tekinay, A. B. (2012). Growth factor binding on heparin mimetic peptide nanofibers. Biomacromolecules, 13(10), 3311-3319.
- Mammadov, R., Mammadov, B., Toksoz, S., Aydin, B., Yagci, R., Tekinay, A. B., & Guler, M. O. (2011). Heparin mimetic peptide nanofibers promote angiogenesis. Biomacromolecules, 12(10), 3508-3519.
- Nune, M., Kumaraswamy, P., Maheswari Krishnan, U., & Sethuraman, S. (2013). Self-assembling peptide nanofibrous scaffolds for tissue engineering: novel approaches and strategies for effective functional regeneration. Current Protein and Peptide Science, 14(1), 70-84.
- Onak, G., Gökmen, O., Yaralı, Z. B., & Karaman, O. (2020). Enhanced osteogenesis of human mesenchymal stem cells by self‐assembled peptide hydrogel functionalized with glutamic acid templated peptides. Journal of Tissue Engineering and Regenerative Medicine, 14(9), 1236-1249.
- Onak, G., & Karaman, O. (2019). Accelerated mineralization on nanofibers via non-thermal atmospheric plasma assisted glutamic acid templated peptide conjugation. Regenerative biomaterials, 6(4), 231-240.
- Onak, G., Şen, M., Horzum, N., Ercan, U. K., Yaralı, Z. B., Garipcan, B., & Karaman, O. (2018). Aspartic and glutamic acid templated peptides conjugation on plasma modified nanofibers for osteogenic differentiation of human mesenchymal stem cells: a comparative study. Scientific reports, 8(1), 1-15.
- Onak Pulat, G., Gökmen, O., Çevik, Z. B. Y., & Karaman, O. (2021). Role of functionalized self-assembled peptide hydrogels in in vitro vasculogenesis. Soft Matter, 17(27), 6616-6626. doi:10.1039/d1sm00680k
- Parmar, P. A., Chow, L. W., St-Pierre, J.-P., Horejs, C.-M., Peng, Y. Y., Werkmeister, J. A., . . . Stevens, M. M. (2015). Collagen-mimetic peptide-modifiable hydrogels for articular cartilage regeneration. Biomaterials, 54, 213-225.
- Pérez, C. M. R., Stephanopoulos, N., Sur, S., Lee, S. S., Newcomb, C., & Stupp, S. I. (2015). The powerful functions of peptide-based bioactive matrices for regenerative medicine. Annals of biomedical engineering, 43(3), 501-514.
- Sendemir‐Urkmez, A., & Jamison, R. D. (2007). The addition of biphasic calcium phosphate to porous chitosan scaffolds enhances bone tissue development in vitro. Journal of Biomedical Materials Research Part A, 81(3), 624-633.
- Sun, J., & Zheng, Q. (2009). Experimental study on self-assembly of KLD-12 peptide hydrogel and 3-D culture of MSC encapsulated within hydrogel in vitro. Journal of Huazhong University of Science and Technology [Medical Sciences], 29(4), 512-516.
- Sun, J., Zheng, Q., Wu, Y., Liu, Y., Guo, X., & Wu, W. (2010). Biocompatibility of KLD-12 peptide hydrogel as a scaffold in tissue engineering of intervertebral discs in rabbits. Journal of Huazhong University of Science and Technology [Medical Sciences], 30(2), 173-177.
- Uzunalli, G., Mammadov, R., Yesildal, F., Alhan, D., Ozturk, S., Ozgurtas, T., . . . Tekinay, A. B. (2017). Angiogenic heparin-mimetic peptide nanofiber gel improves regenerative healing of acute wounds. ACS Biomaterials Science & Engineering, 3(7), 1296-1303.
- Vedadghavami, A., Minooei, F., Mohammadi, M. H., Khetani, S., Kolahchi, A. R., Mashayekhan, S., & Sanati-Nezhad, A. (2017). Manufacturing of hydrogel biomaterials with controlled mechanical properties for tissue engineering applications. Acta biomaterialia, 62, 42-63.
- Vinatier, C., & Guicheux, J. (2016). Cartilage tissue engineering: From biomaterials and stem cells to osteoarthritis treatments. Annals of physical and rehabilitation medicine, 59(3), 139-144.
- Wang, M., Liu, X., Lyu, Z., Gu, H., Li, D., & Chen, H. (2017). Glycosaminoglycans (GAGs) and GAG mimetics regulate the behavior of stem cell differentiation. Colloids and Surfaces B: Biointerfaces, 150, 175-182.
- Webber, M. J., Kessler, J., & Stupp, S. (2010). Emerging peptide nanomedicine to regenerate tissues and organs. Journal of internal medicine, 267(1), 71-88.
- Wei, W., Ma, Y., Yao, X., Zhou, W., Wang, X., Li, C., . . . Ouyang, H. (2021). Advanced hydrogels for the repair of cartilage defects and regeneration. Bioactive Materials, 6(4), 998-1011.
- Wu, S.-C., Huang, P.-Y., Chen, C.-H., Teong, B., Chen, J.-W., Wu, C.-W., . . . Ho, M.-L. (2018). Hyaluronan microenvironment enhances cartilage regeneration of human adipose-derived stem cells in a chondral defect model. International journal of biological macromolecules, 119, 726-740.
- Yang, J., Zhang, Y. S., Yue, K., & Khademhosseini, A. (2017). Cell-laden hydrogels for osteochondral and cartilage tissue engineering. Acta biomaterialia, 57, 1-25.
- Yaylaci, S. U., Sen, M., Bulut, O., Arslan, E., Guler, M. O., & Tekinay, A. B. (2016). Chondrogenic differentiation of mesenchymal stem cells on glycosaminoglycan-mimetic peptide nanofibers. ACS Biomaterials Science & Engineering, 2(5), 871-878.
Heparin Mimetik Peptid ile Modifiye Edilmiş Kendiliğinden Yapılanan Peptid Hidrojel ile İnsan Mezenkimal Kök Hücrelerinin Çoğalma Kinetiğinin Arttırılması
Year 2022,
Issue: 41, 59 - 66, 30.11.2022
Gülşah Sunal
,
Günnur Onak Pulat
,
Ozan Karaman
Abstract
Doğal hücre dışı matris (HDM) bileşenlerinin rolünü taklit eden üç boyutlu (3B) mikro ortamların geliştirilmesi çok önemlidir. Kendiliğinden yapılanan peptit (KYP) hidrojeller, hücrelerin enkapsülasyonu, 3B kültürü, çoğalması ve farklılaşması için ve ayrıca kıkırdak dokusundaki kusurları onarmak için yapı iskeleleri olarak kullanılmıştır. KYP'ler, biyomimetik yapı iskeleleri oluşturmak için kısa peptit epitopları ile biyofonksiyonelleştirilebilir. Burada, KLD (KLDLKLDLKLDL) KYP, KLD-HM (KLDLKLDLKLDL-EGDK) KYP hidrojeli üretmek için kısa bir biyoaktif motif olan EGDK ile işlevselleştirildi ve kendiliğinden yapılandırıldı. Bu çalışmada, geliştirilen KLD-HM KYP hidrojellerinin insan mezenkimal kök hücrelerinin (iMKH'ler) canlılığı ve proliferasyonu üzerindeki etkisinin araştırılması amaçlanmıştır. KYP'lerin stabilitesini sağlamak için, üretilen KYP hidrojellerin reolojik özellikleri ve bozunma profili değerlendirildi. iMKH'lerin KYP hidrojelleri içerisine enkapsüle edilmesinden sonra, MTT tahlili ve Canlı ve Ölü boyama tahlili yapıldı. Bu biyomimetik peptit hidrojel iskelelerinin, enkapsüle edilmiş iMKH'ler için uygun bir mikro ortam sağladığını ve geliştirilen KYP hidrojellerinin iMKH'lerin yapışmasını, canlılığını ve çoğalmasını desteklediğini gösterdik. Sonuçlarımız, tasarlanmış olan biyoaktif SAP hidrojel iskelelerinin kıkırdak dokusunun yenilenmesini teşvik etmek için yararlı olabileceğini düşündürmektedir.
Project Number
Authors acknowledge funding from TÜBİTAK (The Scientific and Technological Research Council of Turkey) in the scope of 2209-A University Students Research Projects Support Program and TÜBİTAK 1002 Program (Project No:121S133).
References
- Arslan, E., Guler, M. O., & Tekinay, A. B. (2016). Glycosaminoglycan-mimetic signals direct the osteo/chondrogenic differentiation of mesenchymal stem cells in a three-dimensional peptide nanofiber extracellular matrix mimetic environment. Biomacromolecules, 17(4), 1280-1291.
- Arslan, E., Üstün Yaylacı, S., Güler, M. O., & Tekinay, A. B. (2016). Therapeutic nanomaterials for cartilage regeneration. In Therapeutic nanomaterials (pp. 59-85): Wiley Online Library.
- Barati, D., Moeinzadeh, S., Karaman, O., & Jabbari, E. (2014). Time dependence of material properties of polyethylene glycol hydrogels chain extended with short hydroxy acid segments. Polymer (Guildf), 55(16), 3894-3904.
- Carballo, C. B., Nakagawa, Y., Sekiya, I., & Rodeo, S. A. (2017). Basic science of articular cartilage. Clinics in sports medicine, 36(3), 413-425.
- Chung, C., & Burdick, J. A. (2008). Engineering cartilage tissue. Advanced drug delivery reviews, 60(2), 243-262.
- Dikecoglu, F. B., Topal, A. E., Ozkan, A. D., Tekin, E. D., Tekinay, A. B., Guler, M. O., & Dana, A. (2018). Force and time-dependent self-assembly, disruption and recovery of supramolecular peptide amphiphile nanofibers. Nanotechnology, 29(28), 285701.
- Eren Cimenci, C., Kurtulus, G. U., Caliskan, O. S., Guler, M. O., & Tekinay, A. B. (2019). N-cadherin mimetic peptide nanofiber system induces chondrogenic differentiation of mesenchymal stem cells. Bioconjugate chemistry, 30(9), 2417-2426.
- Jackson, R. L., Busch, S. J., & Cardin, A. D. (1991). Glycosaminoglycans: molecular properties, protein interactions, and role in physiological processes. Physiological reviews, 71(2), 481-539.
- Karaman, K., Kumar, A., He, X., & Jabbari, E. (2012). Glutamic acid grafted nanofibers as a biomimetic template for mineralization and osteogenic differentiation of mesenchymal stem cells. Paper presented at the Journal of tissue engineering and regenerative medicine.
- Karaman, O., Kumar, A., Moeinzadeh, S., He, X., Cui, T., & Jabbari, E. (2016). Effect of surface modification of nanofibres with glutamic acid peptide on calcium phosphate nucleation and osteogenic differentiation of marrow stromal cells. Journal of tissue engineering and regenerative medicine, 10(2), E132-E146.
- Kisiday, J., Jin, M., Kurz, B., Hung, H., Semino, C., Zhang, S., & Grodzinsky, A. (2002). Self-assembling peptide hydrogel fosters chondrocyte extracellular matrix production and cell division: implications for cartilage tissue repair. Proceedings of the National Academy of Sciences, 99(15), 9996-10001.
- Kocabey, S., Ceylan, H., Tekinay, A. B., & Guler, M. O. (2013). Glycosaminoglycan mimetic peptide nanofibers promote mineralization by osteogenic cells. Acta biomaterialia, 9(11), 9075-9085.
- Koch, F., Müller, M., König, F., Meyer, N., Gattlen, J., Pieles, U., . . . Saxer, S. (2018). Mechanical characteristics of beta sheet-forming peptide hydrogels are dependent on peptide sequence, concentration and buffer composition. Royal Society open science, 5(3), 171562-171562. doi:10.1098/rsos.171562
- Kokubo, T., & Takadama, H. (2006). Leading Opinion. How useful is SBF in predicting in vivo bone bioactivity, Biomaterial, 27, 2907-2915.
- Li, R., Xu, J., Wong, D. S. H., Li, J., Zhao, P., & Bian, L. (2017). Self-assembled N-cadherin mimetic peptide hydrogels promote the chondrogenesis of mesenchymal stem cells through inhibition of canonical Wnt/β-catenin signaling. Biomaterials, 145, 33-43.
- Lim, E.-H., Sardinha, J. P., & Myers, S. (2014). Nanotechnology biomimetic cartilage regenerative scaffolds. Archives of plastic surgery, 41(3), 231.
- Liu, M., Zeng, X., Ma, C., Yi, H., Ali, Z., Mou, X., . . . He, N. (2017). Injectable hydrogels for cartilage and bone tissue engineering. Bone research, 5(1), 1-20.
- Liu, S. Q., Tian, Q., Hedrick, J. L., Hui, J. H. P., Ee, P. L. R., & Yang, Y. Y. (2010). Biomimetic hydrogels for chondrogenic differentiation of human mesenchymal stem cells to neocartilage. Biomaterials, 31(28), 7298-7307.
- Lu, J., & Wang, X. (2018). Biomimetic self-assembling peptide hydrogels for tissue engineering applications. Biomimetic Medical Materials, 297-312.
- Lum, L., & Elisseeff, J. (2003). Injectable hydrogels for cartilage tissue engineering. Topics in tissue engineering, 1.
Mammadov, R., Mammadov, B., Guler, M. O., & Tekinay, A. B. (2012). Growth factor binding on heparin mimetic peptide nanofibers. Biomacromolecules, 13(10), 3311-3319.
- Mammadov, R., Mammadov, B., Toksoz, S., Aydin, B., Yagci, R., Tekinay, A. B., & Guler, M. O. (2011). Heparin mimetic peptide nanofibers promote angiogenesis. Biomacromolecules, 12(10), 3508-3519.
- Nune, M., Kumaraswamy, P., Maheswari Krishnan, U., & Sethuraman, S. (2013). Self-assembling peptide nanofibrous scaffolds for tissue engineering: novel approaches and strategies for effective functional regeneration. Current Protein and Peptide Science, 14(1), 70-84.
- Onak, G., Gökmen, O., Yaralı, Z. B., & Karaman, O. (2020). Enhanced osteogenesis of human mesenchymal stem cells by self‐assembled peptide hydrogel functionalized with glutamic acid templated peptides. Journal of Tissue Engineering and Regenerative Medicine, 14(9), 1236-1249.
- Onak, G., & Karaman, O. (2019). Accelerated mineralization on nanofibers via non-thermal atmospheric plasma assisted glutamic acid templated peptide conjugation. Regenerative biomaterials, 6(4), 231-240.
- Onak, G., Şen, M., Horzum, N., Ercan, U. K., Yaralı, Z. B., Garipcan, B., & Karaman, O. (2018). Aspartic and glutamic acid templated peptides conjugation on plasma modified nanofibers for osteogenic differentiation of human mesenchymal stem cells: a comparative study. Scientific reports, 8(1), 1-15.
- Onak Pulat, G., Gökmen, O., Çevik, Z. B. Y., & Karaman, O. (2021). Role of functionalized self-assembled peptide hydrogels in in vitro vasculogenesis. Soft Matter, 17(27), 6616-6626. doi:10.1039/d1sm00680k
- Parmar, P. A., Chow, L. W., St-Pierre, J.-P., Horejs, C.-M., Peng, Y. Y., Werkmeister, J. A., . . . Stevens, M. M. (2015). Collagen-mimetic peptide-modifiable hydrogels for articular cartilage regeneration. Biomaterials, 54, 213-225.
- Pérez, C. M. R., Stephanopoulos, N., Sur, S., Lee, S. S., Newcomb, C., & Stupp, S. I. (2015). The powerful functions of peptide-based bioactive matrices for regenerative medicine. Annals of biomedical engineering, 43(3), 501-514.
- Sendemir‐Urkmez, A., & Jamison, R. D. (2007). The addition of biphasic calcium phosphate to porous chitosan scaffolds enhances bone tissue development in vitro. Journal of Biomedical Materials Research Part A, 81(3), 624-633.
- Sun, J., & Zheng, Q. (2009). Experimental study on self-assembly of KLD-12 peptide hydrogel and 3-D culture of MSC encapsulated within hydrogel in vitro. Journal of Huazhong University of Science and Technology [Medical Sciences], 29(4), 512-516.
- Sun, J., Zheng, Q., Wu, Y., Liu, Y., Guo, X., & Wu, W. (2010). Biocompatibility of KLD-12 peptide hydrogel as a scaffold in tissue engineering of intervertebral discs in rabbits. Journal of Huazhong University of Science and Technology [Medical Sciences], 30(2), 173-177.
- Uzunalli, G., Mammadov, R., Yesildal, F., Alhan, D., Ozturk, S., Ozgurtas, T., . . . Tekinay, A. B. (2017). Angiogenic heparin-mimetic peptide nanofiber gel improves regenerative healing of acute wounds. ACS Biomaterials Science & Engineering, 3(7), 1296-1303.
- Vedadghavami, A., Minooei, F., Mohammadi, M. H., Khetani, S., Kolahchi, A. R., Mashayekhan, S., & Sanati-Nezhad, A. (2017). Manufacturing of hydrogel biomaterials with controlled mechanical properties for tissue engineering applications. Acta biomaterialia, 62, 42-63.
- Vinatier, C., & Guicheux, J. (2016). Cartilage tissue engineering: From biomaterials and stem cells to osteoarthritis treatments. Annals of physical and rehabilitation medicine, 59(3), 139-144.
- Wang, M., Liu, X., Lyu, Z., Gu, H., Li, D., & Chen, H. (2017). Glycosaminoglycans (GAGs) and GAG mimetics regulate the behavior of stem cell differentiation. Colloids and Surfaces B: Biointerfaces, 150, 175-182.
- Webber, M. J., Kessler, J., & Stupp, S. (2010). Emerging peptide nanomedicine to regenerate tissues and organs. Journal of internal medicine, 267(1), 71-88.
- Wei, W., Ma, Y., Yao, X., Zhou, W., Wang, X., Li, C., . . . Ouyang, H. (2021). Advanced hydrogels for the repair of cartilage defects and regeneration. Bioactive Materials, 6(4), 998-1011.
- Wu, S.-C., Huang, P.-Y., Chen, C.-H., Teong, B., Chen, J.-W., Wu, C.-W., . . . Ho, M.-L. (2018). Hyaluronan microenvironment enhances cartilage regeneration of human adipose-derived stem cells in a chondral defect model. International journal of biological macromolecules, 119, 726-740.
- Yang, J., Zhang, Y. S., Yue, K., & Khademhosseini, A. (2017). Cell-laden hydrogels for osteochondral and cartilage tissue engineering. Acta biomaterialia, 57, 1-25.
- Yaylaci, S. U., Sen, M., Bulut, O., Arslan, E., Guler, M. O., & Tekinay, A. B. (2016). Chondrogenic differentiation of mesenchymal stem cells on glycosaminoglycan-mimetic peptide nanofibers. ACS Biomaterials Science & Engineering, 2(5), 871-878.