Evaluation of a Novel Thiol-Norbornene-Functionalized Gelatin Hydrogel for Bioprinting of Mesenchymal Stem Cells

被引:10
作者
Burchak, Vadym [1 ]
Koch, Fritz [2 ]
Siebler, Leonard [1 ]
Haase, Sonja [3 ]
Horner, Verena K. [1 ]
Kempter, Xenia [3 ]
Stark, G. Bjoern [1 ]
Schepers, Ute [3 ]
Grimm, Alisa [3 ]
Zimmermann, Stefan [2 ]
Koltay, Peter [2 ]
Strassburg, Sandra [1 ]
Finkenzeller, Gunter [1 ]
Simunovic, Filip [1 ]
Lampert, Florian [1 ]
机构
[1] Univ Freiburg, Fac Med, Med Ctr, Dept Plast & Hand Surg, Hugstetter Str 55, D-79106 Freiburg, Germany
[2] Univ Freiburg, IMTEK, Lab MEMS Applicat, Dept Microsyst Engn, Georges Koehler Allee 103, D-79110 Freiburg, Germany
[3] Karlsruhe Inst Technol KIT, Inst Funct Interfaces IFG, Hermann von Helmholtz Pl 1, D-76344 Eggenstein Leopoldshafen, Germany
关键词
cartilage; hydrogel; bioprinting; mesenchymal stem cells; differentiation; biocompatibility; tissue engineering; STROMAL CELLS; BONE-MARROW; RED O; DIFFERENTIATION; BIOMATERIAL; FABRICATION; STIFFNESS; MAINTAIN; DEFECTS; REPAIR;
D O I
10.3390/ijms23147939
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Introduction: Three-dimensional bioprinting can be considered as an advancement of the classical tissue engineering concept. For bioprinting, cells have to be dispersed in hydrogels. Recently, a novel semi-synthetic thiolene hydrogel system based on norbornene-functionalized gelatin (GelNB) and thiolated gelatin (GelS) was described that resulted in the photoclick hydrogel GelNB/GelS. In this study, we evaluated the printability and biocompatibility of this hydrogel system towards adipose-tissue-derived mesenchymal stem cells (ASCs). Methods: GelNB/GelS was synthesized with three different crosslinking densities (low, medium and high), resulting in different mechanical properties with moduli of elasticity between 206 Pa and 1383 Pa. These hydrogels were tested for their biocompatibility towards ASCs in terms of their viability, proliferation and differentiation. The extrusion-based bioprinting of ASCs in GelNB/GelS-high was performed to manufacture three-dimensional cubic constructs. Results: All three hydrogels supported the viability, proliferation and chondrogenic differentiation of ASCs to a similar extent. The adipogenic differentiation of ASCs was better supported by the softer hydrogel (GelNB/GelS-low), whereas the osteogenic differentiation was more pronounced in the harder hydrogel (GelNB/GelS-high), indicating that the differentiation fate of ASCs can be influenced via the adaption of the mechanical properties of the GelNB/GelS system. After the ex vivo chondrogenic differentiation and subcutaneous implantation of the bioprinted construct into immunocompromised mice, the production of negatively charged sulfated proteoglycans could be observed with only minimal inflammatory signs in the implanted material. Conclusions: Our results indicate that the GelNB/GelS hydrogels are very well suited for the bioprinting of ASCs and may represent attractive hydrogels for subsequent in vivo tissue engineering applications.
引用
收藏
页数:23
相关论文
共 47 条
[21]   SPECIFIC STAINING OF SULPHATE GROUPS WITH ALCIAN BLUE AT LOW PH [J].
LEV, R ;
SPICER, SS .
JOURNAL OF HISTOCHEMISTRY & CYTOCHEMISTRY, 1964, 12 (04) :309-&
[22]   Biomaterial stiffness determines stem cell fate [J].
Lv, Hongwei ;
Wang, Heping ;
Zhang, Zhijun ;
Yang, Wang ;
Liu, Wenbin ;
Li, Yulin ;
Li, Lisha .
LIFE SCIENCES, 2017, 178 :42-48
[23]   Thiol-Ene Photopolymerizations Provide a Facile Method To Encapsulate Proteins and Maintain Their Bioactivity [J].
McCall, Joshua D. ;
Anseth, Kristi S. .
BIOMACROMOLECULES, 2012, 13 (08) :2410-2417
[24]   Imaging of neutral lipids by oil red O for analyzing the metabolic status in health and disease [J].
Mehlem, Annika ;
Hagberg, Carolina E. ;
Muhl, Lars ;
Eriksson, Ulf ;
Falkevall, Annelie .
NATURE PROTOCOLS, 2013, 8 (06) :1149-1154
[25]   Adipose-derived and bone marrow mesenchymal stem cells: a donor-matched comparison [J].
Mohamed-Ahmed, Samih ;
Fristad, Inge ;
Lie, Stein Atle ;
Suliman, Salwa ;
Mustafa, Kamal ;
Vindenes, Hallvard ;
Idris, Shaza B. .
STEM CELL RESEARCH & THERAPY, 2018, 9
[26]   Gelatin hydrogels formed by orthogonal thiol-norbornene photochemistry for cell encapsulation [J].
Munoz, Zachary ;
Shih, Han ;
Lin, Chien-Chi .
BIOMATERIALS SCIENCE, 2014, 2 (08) :1063-1072
[27]   3D bioprinting of tissues and organs [J].
Murphy, Sean V. ;
Atala, Anthony .
NATURE BIOTECHNOLOGY, 2014, 32 (08) :773-785
[28]   A Systemic Review of Adult Mesenchymal Stem Cell Sources and their Multilineage Differentiation Potential Relevant to Musculoskeletal Tissue Repair and Regeneration [J].
Nancarrow-Lei, Rhiannon ;
Mafi, Pouya ;
Mafi, Reza ;
Khan, Wasim .
CURRENT STEM CELL RESEARCH & THERAPY, 2017, 12 (08) :601-610
[29]   3D Photo-Fabrication for Tissue Engineering and Drug Delivery [J].
Pereira, Ruben F. ;
Bartolo, Paulo J. .
ENGINEERING, 2015, 1 (01) :90-112
[30]   Multilineage potential of adult human mesenchymal stem cells [J].
Pittenger, MF ;
Mackay, AM ;
Beck, SC ;
Jaiswal, RK ;
Douglas, R ;
Mosca, JD ;
Moorman, MA ;
Simonetti, DW ;
Craig, S ;
Marshak, DR .
SCIENCE, 1999, 284 (5411) :143-147