Injectable shear-thinning hydrogels for delivering osteogenic and angiogenic cells and growth factors

被引:79
作者
Alarcin, Emine [1 ,2 ,3 ]
Lee, Tae Yong [1 ,2 ,4 ]
Karuthedom, Sobha [1 ,2 ]
Mohammadi, Marzieh [1 ,2 ]
Brennan, Meadhbh A. [1 ,2 ,5 ]
Lee, Dong Hoon [1 ,2 ]
Marrella, Alessandra [1 ,2 ]
Zhang, Jin [1 ,2 ]
Syla, Denata [1 ,2 ]
Zhang, Yu Shrike [1 ,2 ,6 ]
Khademhosseini, Ali [1 ,2 ,6 ,7 ,8 ,9 ,10 ,11 ,12 ]
Jang, Hae Lin [1 ,2 ,6 ]
机构
[1] Harvard Med Sch, Brigham & Womens Hosp, Dept Med, Div Engn Med, Cambridge, MA 02139 USA
[2] Harvard, MIT, Div Hlth Sci & Technol, Cambridge, MA 02139 USA
[3] Marmara Univ, Dept Pharmaceut Technol, Fac Pharm, TR-34668 Istanbul, Turkey
[4] Korea Adv Inst Sci & Technol, Dept Chem & Biomol Engn, Daejeon 34141, South Korea
[5] Univ Nantes, Fac Med, PHYOS, INSERM,UMR 1238, Nantes, France
[6] Harvard Univ, Wyss Inst Biol Inspired Engn, Boston, MA 02115 USA
[7] Konkuk Univ, Coll Anim Biosci & Technol, Dept Bioind Technol, Seoul 143701, South Korea
[8] King Abdulaziz Univ, Dept Phys, Ctr Nanotechnol, Jeddah 21569, Saudi Arabia
[9] Univ Calif Los Angeles, Henry Samueli Sch Engn & Appl Sci, Dept Chem & Biomol Engn, Dept Bioengn, Los Angeles, CA USA
[10] Univ Calif Los Angeles, David Geffen Sch Med, Dept Radiol, Los Angeles, CA 90095 USA
[11] Univ Calif Los Angeles, Ctr Minimally Invas Therapeut C MIT, Los Angeles, CA USA
[12] Univ Calif Los Angeles, Calif NanoSyst Inst CNSI, Los Angeles, CA USA
基金
欧盟地平线“2020”;
关键词
MESENCHYMAL STEM-CELLS; LOADED PLGA NANOPARTICLES; IN-VITRO; ENGINEERING STRATEGIES; AVASCULAR NECROSIS; CONTROLLED-RELEASE; ENDOTHELIAL-CELLS; BONE REPAIR; DIFFERENTIATION; VASCULARIZATION;
D O I
10.1039/c8bm00293b
中图分类号
TB3 [工程材料学]; R318.08 [生物材料学];
学科分类号
0805 ; 080501 ; 080502 ;
摘要
Bone nonunion may occur when the fracture is unstable, or blood supply is impeded. To provide an effective treatment for the healing of nonunion defects, we introduce an injectable osteogenic hydrogel that can deliver cells and vasculogenic growth factors. We used a silicate-based shear-thinning hydrogel (STH) to engineer an injectable scaffold and incorporated polycaprolactone (PCL) nanoparticles that entrap and release vasculogenic growth factors in a controlled manner. By adjusting the solid composition of gelatin and silicate nanoplatelets in the STH, we defined optimal conditions that enable injection of STHs, which can deliver cells and growth factors. Different types of STHs could be simultaneously injected into 3D constructs through a single extrusion head composed of multiple syringes and needles, while maintaining their engineered structure in a continuous manner. The injected STHs were also capable of filling any irregularly shaped defects in bone. Osteogenic cells and endothelial cells were encapsulated in STHs with and without vasculogenic growth factors, respectively, and when co-cultured, their growth and differentiation were significantly enhanced compared to cells grown in monoculture. This study introduces an initial step of developing a new platform of shape-tunable materials with controlled release of angiogenic growth factors by utilizing PCL nanoparticles.
引用
收藏
页码:1604 / 1615
页数:12
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