scholarly journals Scaffold-free human mesenchymal stem cell construct geometry regulates long bone regeneration

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Samuel Herberg ◽  
Daniel Varghai ◽  
Daniel S. Alt ◽  
Phuong N. Dang ◽  
Honghyun Park ◽  
...  

AbstractBiomimetic bone tissue engineering strategies partially recapitulate development. We recently showed functional restoration of femoral defects using scaffold-free human mesenchymal stem cell (hMSC) condensates featuring localized morphogen presentation with delayed in vivo mechanical loading. Possible effects of construct geometry on healing outcome remain unclear. Here, we hypothesized that localized presentation of transforming growth factor (TGF)-β1 and bone morphogenetic protein (BMP)-2 to engineered hMSC tubes mimicking femoral diaphyses induces endochondral ossification, and that TGF-β1 + BMP-2-presenting hMSC tubes enhance defect healing with delayed in vivo loading vs. loosely packed hMSC sheets. Localized morphogen presentation stimulated chondrogenic priming/endochondral differentiation in vitro. Subcutaneously, hMSC tubes formed cartilage templates that underwent bony remodeling. Orthotopically, hMSC tubes stimulated more robust endochondral defect healing vs. hMSC sheets. Tissue resembling normal growth plate was observed with negligible ectopic bone. This study demonstrates interactions between hMSC condensation geometry, morphogen bioavailability, and mechanical cues to recapitulate development for biomimetic bone tissue engineering.

Micromachines ◽  
2019 ◽  
Vol 11 (1) ◽  
pp. 31 ◽  
Author(s):  
Shen Ji ◽  
Murat Guvendiren

There is a growing interest in developing 3D porous scaffolds with tunable architectures for bone tissue engineering. Surface topography has been shown to control stem cell behavior including differentiation. In this study, we printed 3D porous scaffolds with wavy or linear patterns to investigate the effect of wavy scaffold architecture on human mesenchymal stem cell (hMSC) osteogenesis. Five distinct wavy scaffolds were designed using sinusoidal waveforms with varying wavelengths and amplitudes, and orthogonal scaffolds were designed using linear patterns. We found that hMSCs attached to wavy patterns, spread by taking the shape of the curvatures presented by the wavy patterns, exhibited an elongated shape and mature focal adhesion points, and differentiated into the osteogenic lineage. When compared to orthogonal scaffolds, hMSCs on wavy scaffolds showed significantly enhanced osteogenesis, indicated by higher calcium deposition, alkaline phosphatase activity, and osteocalcin staining. This study aids in the development of 3D scaffolds with novel architectures to direct stem osteogenesis for bone tissue engineering.


2020 ◽  
Vol 1 ◽  
Author(s):  
Ruth Tevlin ◽  
Michael T. Longaker ◽  
Derrick C. Wan

Defects of the craniofacial skeleton arise as a direct result of trauma, diseases, oncological resection, or congenital anomalies. Current treatment options are limited, highlighting the importance for developing new strategies to restore form, function, and aesthetics of missing or damaged bone in the face and the cranium. For optimal reconstruction, the goal is to replace “like with like.” With the inherent challenges of existing options, there is a clear need to develop alternative strategies to reconstruct the craniofacial skeleton. The success of mesenchymal stem cell-based approaches has been hampered by high heterogeneity of transplanted cell populations with inconsistent preclinical and clinical trial outcomes. Here, we discuss the novel characterization and isolation of mouse skeletal stem cell (SSC) populations and their response to injury, systemic disease, and how their re-activation in vivo can contribute to tissue regeneration. These studies led to the characterization of human SSCs which are able to self-renew, give rise to increasingly fate restricted progenitors, and differentiate into bone, cartilage, and bone marrow stroma, all on the clonal level in vivo without prior in vitro culture. SSCs hold great potential for implementation in craniofacial bone tissue engineering and regenerative medicine. As we begin to better understand the diversity and the nature of skeletal stem and progenitor cells, there is a tangible future whereby a subset of human adult SSCs can be readily purified from bone or activated in situ with broad potential applications in craniofacial tissue engineering.


2010 ◽  
Vol 16 (2) ◽  
pp. 225-235 ◽  
Author(s):  
Barbara Pui Chan ◽  
Ting Yan Hui ◽  
Mei Yi Wong ◽  
Kevin Hak Kong Yip ◽  
Godfrey Chi Fung Chan

2019 ◽  
Vol 11 (9) ◽  
pp. 8749-8762 ◽  
Author(s):  
Chen Zhao ◽  
Nader Taheri Qazvini ◽  
Monirosadat Sadati ◽  
Zongyue Zeng ◽  
Shifeng Huang ◽  
...  

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