Hydrogels that mimic developmentally relevant matrix and N-cadherin interactions enhance MSC chondrogenesis

被引:335
作者
Bian, Liming [1 ,3 ]
Guvendiren, Murat [1 ]
Mauck, Robert L. [1 ,2 ]
Burdick, Jason A. [1 ]
机构
[1] Univ Penn, Perelman Sch Med, Dept Bioengn, Philadelphia, PA 19104 USA
[2] Univ Penn, Perelman Sch Med, Dept Orthopaed Surg, Philadelphia, PA 19104 USA
[3] Chinese Univ Hong Kong, Dept Mech & Automat Engn, Div Biomed Engn, Sheitin, Hong Kong, Peoples R China
基金
美国国家卫生研究院;
关键词
MESENCHYMAL STEM-CELLS; HYALURONIC-ACID HYDROGELS; IN-VITRO CHONDROGENESIS; EXTRACELLULAR-MATRIX; LIMB CHONDROGENESIS; TRANSIENT EXPOSURE; BETA-CATENIN; EXPRESSION; DIFFERENTIATION; ADHESION;
D O I
10.1073/pnas.1214100110
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Methacrylated hyaluronic acid (HA) hydrogels provide a backbone polymer with which mesenchymal stem cells (MSCs) can interact through several cell surface receptors that are expressed by MSCs, including CD44 and CD168. Previous studies showed that this 3D hydrogel environment supports the chondrogenesis of MSCs, and here we demonstrate through functional blockade that these specific cell-material interactions play a role in this process. Beyond matrix interactions, cadherin molecules, a family of transmembrane glycoproteins, play a critical role in tissue development during embryogenesis, and N-cadherin is a key factor in mediating cell-cell interactions during mesenchymal condensation and chondrogenesis. In this study, we functionalized HA hydrogels with N-cadherin mimetic peptides and evaluated their role in regulating chondrogenesis and cartilage matrix deposition by encapsulated MSCs. Our results show that conjugation of cadherin peptides onto HA hydrogels promotes both early chondrogenesis of MSCs and cartilage-specific matrix production with culture, compared with unmodified controls or those with inclusion of a scrambled peptide domain. This enhanced chondrogenesis was abolished via treatment with N-cadherin-specific antibodies, confirming the contribution of these N-cadherin peptides to chondrogenesis. Subcutaneous implantation of MSC-seeded constructs also showed superior neocartilage formation in implants functionalized with N-cadherin mimetic peptides compared with controls. This study demonstrates the inherent biologic activity of HA-based hydrogels, as well as the promise of biofunctionalizing HA hydrogels to emulate the complexity of the natural cell microenvironment during embryogenesis, particularly in stem cell-based cartilage regeneration.
引用
收藏
页码:10117 / 10122
页数:6
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