Hydrogels that mimic developmentally relevant matrix and N-cadherin interactions enhance MSC chondrogenesis
被引:335
作者:
Bian, Liming
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Univ Penn, Perelman Sch Med, Dept Bioengn, Philadelphia, PA 19104 USA
Chinese Univ Hong Kong, Dept Mech & Automat Engn, Div Biomed Engn, Sheitin, Hong Kong, Peoples R ChinaUniv Penn, Perelman Sch Med, Dept Bioengn, Philadelphia, PA 19104 USA
Bian, Liming
[1
,3
]
Guvendiren, Murat
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Univ Penn, Perelman Sch Med, Dept Bioengn, Philadelphia, PA 19104 USAUniv Penn, Perelman Sch Med, Dept Bioengn, Philadelphia, PA 19104 USA
Guvendiren, Murat
[1
]
Mauck, Robert L.
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机构:
Univ Penn, Perelman Sch Med, Dept Bioengn, Philadelphia, PA 19104 USA
Univ Penn, Perelman Sch Med, Dept Orthopaed Surg, Philadelphia, PA 19104 USAUniv Penn, Perelman Sch Med, Dept Bioengn, Philadelphia, PA 19104 USA
Mauck, Robert L.
[1
,2
]
Burdick, Jason A.
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Univ Penn, Perelman Sch Med, Dept Bioengn, Philadelphia, PA 19104 USAUniv Penn, Perelman Sch Med, Dept Bioengn, Philadelphia, PA 19104 USA
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
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.
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Univ Penn, Dept Bioengn, Philadelphia, PA 19104 USAUniv Penn, Dept Bioengn, Philadelphia, PA 19104 USA
Bian, Liming
Zhai, David Y.
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Univ Penn, Dept Bioengn, Philadelphia, PA 19104 USAUniv Penn, Dept Bioengn, Philadelphia, PA 19104 USA
Zhai, David Y.
Tous, Elena
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Univ Penn, Dept Bioengn, Philadelphia, PA 19104 USAUniv Penn, Dept Bioengn, Philadelphia, PA 19104 USA
Tous, Elena
Rai, Reena
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Univ Penn, Dept Bioengn, Philadelphia, PA 19104 USAUniv Penn, Dept Bioengn, Philadelphia, PA 19104 USA
Rai, Reena
Mauck, Robert L.
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机构:
Univ Penn, Dept Bioengn, Philadelphia, PA 19104 USA
Univ Penn, Dept Orthoped Surg, McKay Orthoped Res Lab, Philadelphia, PA 19104 USAUniv Penn, Dept Bioengn, Philadelphia, PA 19104 USA
Mauck, Robert L.
Burdick, Jason A.
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Univ Penn, Dept Bioengn, Philadelphia, PA 19104 USAUniv Penn, Dept Bioengn, Philadelphia, PA 19104 USA
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Univ Penn, Dept Bioengn, Philadelphia, PA 19104 USAUniv Penn, Dept Bioengn, Philadelphia, PA 19104 USA
Chung, Cindy
Beecham, Michael
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Univ Penn, Dept Bioengn, Philadelphia, PA 19104 USAUniv Penn, Dept Bioengn, Philadelphia, PA 19104 USA
Beecham, Michael
Mauck, Robert L.
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机构:
Univ Penn, Dept Bioengn, Philadelphia, PA 19104 USA
Univ Penn, Dept Orthopaed Surg, McKay Orthopaed Res Lab, Philadelphia, PA 19104 USAUniv Penn, Dept Bioengn, Philadelphia, PA 19104 USA
Mauck, Robert L.
Burdick, Jason A.
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机构:
Univ Penn, Dept Bioengn, Philadelphia, PA 19104 USAUniv Penn, Dept Bioengn, Philadelphia, PA 19104 USA
机构:
Univ Penn, Dept Bioengn, Philadelphia, PA 19104 USAUniv Penn, Dept Bioengn, Philadelphia, PA 19104 USA
Bian, Liming
Zhai, David Y.
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机构:
Univ Penn, Dept Bioengn, Philadelphia, PA 19104 USAUniv Penn, Dept Bioengn, Philadelphia, PA 19104 USA
Zhai, David Y.
Tous, Elena
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h-index: 0
机构:
Univ Penn, Dept Bioengn, Philadelphia, PA 19104 USAUniv Penn, Dept Bioengn, Philadelphia, PA 19104 USA
Tous, Elena
Rai, Reena
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h-index: 0
机构:
Univ Penn, Dept Bioengn, Philadelphia, PA 19104 USAUniv Penn, Dept Bioengn, Philadelphia, PA 19104 USA
Rai, Reena
Mauck, Robert L.
论文数: 0引用数: 0
h-index: 0
机构:
Univ Penn, Dept Bioengn, Philadelphia, PA 19104 USA
Univ Penn, Dept Orthoped Surg, McKay Orthoped Res Lab, Philadelphia, PA 19104 USAUniv Penn, Dept Bioengn, Philadelphia, PA 19104 USA
Mauck, Robert L.
Burdick, Jason A.
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h-index: 0
机构:
Univ Penn, Dept Bioengn, Philadelphia, PA 19104 USAUniv Penn, Dept Bioengn, Philadelphia, PA 19104 USA
机构:
Univ Penn, Dept Bioengn, Philadelphia, PA 19104 USAUniv Penn, Dept Bioengn, Philadelphia, PA 19104 USA
Chung, Cindy
Beecham, Michael
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h-index: 0
机构:
Univ Penn, Dept Bioengn, Philadelphia, PA 19104 USAUniv Penn, Dept Bioengn, Philadelphia, PA 19104 USA
Beecham, Michael
Mauck, Robert L.
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h-index: 0
机构:
Univ Penn, Dept Bioengn, Philadelphia, PA 19104 USA
Univ Penn, Dept Orthopaed Surg, McKay Orthopaed Res Lab, Philadelphia, PA 19104 USAUniv Penn, Dept Bioengn, Philadelphia, PA 19104 USA
Mauck, Robert L.
Burdick, Jason A.
论文数: 0引用数: 0
h-index: 0
机构:
Univ Penn, Dept Bioengn, Philadelphia, PA 19104 USAUniv Penn, Dept Bioengn, Philadelphia, PA 19104 USA