Three-dimensional printed PLA scaffold and human gingival stem cell-derived extracellular vesicles: a new tool for bone defect repair

被引：201
作者：
Diomede, Francesca [1 ]
Gugliandolo, Agnese [2 ]
Cardelli, Paolo [1 ]
Merciaro, Ilaria [1 ]
Ettorre, Valeria [3 ]
Traini, Tonino [1 ]
Bedini, Rossella [4 ]
Scionti, Domenico [2 ]
Bramanti, Alessia [2 ,5 ]
Nanci, Antonio [6 ]
Caputi, Sergio [1 ]
Fontana, Antonella [3 ]
Mazzon, Emanuela [2 ]
Trubiani, Oriana [7 ]
机构：
[1] Univ G DAnnunzio, Dept Med Oral & Biotechnol Sci, Chieti, Italy
[2] IRCCS Ctr Neurolesi Bonino Pulejo, Messina, Italy
[3] Univ G DAnnunzio, Dept Pharm, Chieti, Italy
[4] Italian Natl Inst Hlth, Natl Ctr Innovat Technol Publ Hlth, Rome, Italy
[5] CNR, Inst Appl Sci & Intelligent Syst ISASI Eduardo Ca, Messina, Italy
[6] Univ Montreal, Fac Dent, Dept Stomatol, Lab Study Calcified Tissues & Biomat, Montreal, PQ, Canada
[7] Univ G DAnnunzio, Dept Med Oral & Biotechnol Sci, Via Vestini, I-66100 Chieti, Italy
来源：
STEM CELL RESEARCH & THERAPY | 2018年 / 9卷
关键词：
Human gingival mesenchymal stem cells; 3D scaffold; Extracellular vesicles; Bone regeneration; HUMAN PERIODONTAL-LIGAMENT; TISSUE-ENGINEERED BONE; PLATELET-RICH PLASMA; IN-VITRO; EXOSOMES; REGENERATION; DEGRADATION; RELEASE; DESIGN; DIFFERENTIATION;
D O I：
10.1186/s13287-018-0850-0
中图分类号：
Q813 [细胞工程];
学科分类号：
摘要：
Background: The role of bone tissue engineering in the field of regenerative medicine has been a main research topic over the past few years. There has been much interest in the use of three-dimensional (3D) engineered scaffolds (PLA) complexed with human gingival mesenchymal stem cells (hGMSCs) as a new therapeutic strategy to improve bone tissue regeneration. These devices can mimic a more favorable endogenous microenvironment for cells in vivo by providing 3D substrates which are able to support cell survival, proliferation and differentiation. The present study evaluated the in vitro and in vivo capability of bone defect regeneration of 3D PLA, hGMSCs, extracellular vesicles (EVs), or polyethyleneimine (PEI)-engineered EVs (PEI-EVs) in the following experimental groups: 3D-PLA, 3D-PLA + hGMSCs, 3D-PLA + EVs, 3D-PLA + EVs + hGMSCs, 3D-PLA + PEI-EVs, 3D-PLA + PEI-EVs + hGMSCs. Methods: The structural parameters of the scaffold were evaluated using both scanning electron microscopy and nondestructive microcomputed tomography. Nanotopographic surface features were investigated by means of atomic force microscopy. Scaffolds showed a statistically significant mass loss along the 112-day evaluation. Results: Our in vitro results revealed that both 3D-PLA + EVs + hGMSCs and 3D-PLA + PEI-EVs + hGMSCs showed no cytotoxicity. However, 3D-PLA + PEI-EVs + hGMSCs exhibited greater osteogenic inductivity as revealed by morphological evaluation and transcriptomic analysis performed by next-generation sequencing (NGS). In addition, in vivo results showed that 3D-PLA + PEI-EVs + hGMSCs and 3D-PLA + PEI-EVs scaffolds implanted in rats subjected to cortical calvaria bone tissue damage were able to improve bone healing by showing better osteogenic properties. These results were supported also by computed tomography evaluation that revealed the repair of bone calvaria damage. Conclusion: The re-establishing of the integrity of the bone lesions could be a promising strategy in the treatment of accidental or surgery trauma, especially for cranial bones.
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页数：21
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