Long-term in vivo integrity and safety of3D-bioprinted cartilaginous constructs

被引:20
作者
Apelgren, Peter [1 ]
Amoroso, Matteo [1 ]
Saljo, Karin [1 ]
Lindahl, Anders [2 ]
Brantsing, Camilla [2 ]
Stridh Orrhult, Linnea [3 ]
Markstedt, Kajsa [3 ]
Gatenholm, Paul [3 ]
Kolby, Lars [1 ]
机构
[1] Univ Gothenburg, Sahlgrenska Univ Hosp, Dept Plast Surg, Sahlgrenska Acad,Inst Clin Sci, Gothenburg, Sweden
[2] Sahlgrens Univ Hosp, Inst Biomed, Dept Clin Chem & Transfus Med, Gothenburg, Sweden
[3] Chalmers Univ Technol, 3D Bioprinting Ctr, Dept Chem & Chem Engn, Gothenburg, Sweden
关键词
3D-bioprinting; cartilage; chondrocytes; in vivo; long-term; nude mice; MESENCHYMAL STEM-CELLS; BALB/C-NU MICE; CHONDROGENIC DIFFERENTIATION; REGENERATIVE MEDICINE; SPONTANEOUS TUMORS; LIFE-SPAN; CHONDROCYTES; RECONSTRUCTION; PROLIFERATION; NANOCELLULOSE;
D O I
10.1002/jbm.b.34687
中图分类号
R318 [生物医学工程];
学科分类号
0831 ;
摘要
Long-term stability and biological safety are crucial for translation of 3D-bioprinting technology into clinical applications. Here, we addressed the long-term safety and stability issues associated with 3D-bioprinted constructs comprising a cellulose scaffold and human cells (chondrocytes and stem cells) over a period of 10 months in nude mice. Our findings showed that increasing unconfined compression strength over time significantly improved the mechanical stability of the cell-containing constructs relative to cell-free scaffolds. Additionally, the cell-free constructs exhibited a mean compressive stress and stiffness (compressive modulus) of 0.04 +/- 0.05 MPa and 0.14 +/- 0.18 MPa, respectively, whereas these values for the cell-containing constructs were 0.11 +/- 0.08 MPa (p= .019) and 0.53 +/- 0.59 MPa (p= .012), respectively. Moreover, histomorphologic analysis revealed that cartilage formed from the cell-containing constructs harbored an abundance of proliferating chondrocytes in clusters, and after 10 months, resembled native cartilage. Furthermore, extension of the experiment over the complete lifecycle of the animal model revealed no signs of ossification, fibrosis, necrosis, or implant-related tumor development in the 3D-bioprinted constructs. These findings confirm the in vivo biological safety and mechanical stability of 3D-bioprinted cartilaginous tissues and support their potential translation into clinical applications.
引用
收藏
页码:128 / 136
页数:9
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