The effects of a 3D-printed magnesium-/strontium-doped calcium silicate scaffold on regulation of bone regeneration via dual-stimulation of the AKT and WNT signaling pathways

Author(s):  
Yen-Hong Lin ◽  
Alvin Kai-Xing Lee ◽  
Chia-Che Ho ◽  
Min-Jie Fang ◽  
Ting-You Kuo ◽  
...  
2019 ◽  
Vol 20 (4) ◽  
pp. 942 ◽  
Author(s):  
Yuan-Haw Wu ◽  
Yung-Cheng Chiu ◽  
Yen-Hong Lin ◽  
Chia-Che Ho ◽  
Ming-You Shie ◽  
...  

Currently, clinically available orthopedic implants are extremely biocompatible but they lack specific biological characteristics that allow for further interaction with surrounding tissues. The extracellular matrix (ECM)-coated scaffolds have received considerable interest for bone regeneration due to their ability in upregulating regenerative cellular behaviors. This study delves into the designing and fabrication of three-dimensional (3D)-printed scaffolds that were made out of calcium silicate (CS), polycaprolactone (PCL), and decellularized ECM (dECM) from MG63 cells, generating a promising bone tissue engineering strategy that revolves around the concept of enhancing osteogenesis by creating an osteoinductive microenvironment with osteogenesis-promoting dECM. We cultured MG63 on scaffolds to obtain a dECM-coated CS/PCL scaffold and further studied the biological performance of the dECM hybrid scaffolds. The results indicated that the dECM-coated CS/PCL scaffolds exhibited excellent biocompatibility and effectively enhanced cellular adhesion, proliferation, and differentiation of human Wharton’s Jelly mesenchymal stem cells by increasing the expression of osteogenic-related genes. They also presented anti-inflammatory characteristics by showing a decrease in the expression of tumor necrosis factor-alpha (TNF-α) and interleukin-1 (IL-1). Histological analysis of in vivo experiments presented excellent bone regenerative capabilities of the dECM-coated scaffold. Overall, our work presented a promising technique for producing bioscaffolds that can augment bone tissue regeneration in numerous aspects.


2010 ◽  
Vol 7 (2) ◽  
pp. 37-46 ◽  
Author(s):  
Wataru Katagiri ◽  
Yoichi Yamada ◽  
Sayaka Nakamura ◽  
Kenji Ito ◽  
Kenji Hara ◽  
...  

2019 ◽  
Vol 20 (11) ◽  
pp. 2729 ◽  
Author(s):  
Yung-Cheng Chiu ◽  
Ming-You Shie ◽  
Yen-Hong Lin ◽  
Alvin Kai-Xing Lee ◽  
Yi-Wen Chen

In this study, we synthesized strontium-contained calcium silicate (SrCS) powder and fabricated SrCS scaffolds with controlled precise structures using 3D printing techniques. SrCS scaffolds were shown to possess increased mechanical properties as compared to calcium silicate (CS) scaffolds. Our results showed that SrCS scaffolds had uniform interconnected macropores (~500 µm) with a compressive strength 2-times higher than that of CS scaffolds. The biological behaviors of SrCS scaffolds were assessed using the following characteristics: apatite-precipitating ability, cytocompatibility, proliferation, and osteogenic differentiation of human mesenchymal stem cells (MSCs). With CS scaffolds as controls, our results indicated that SrCS scaffolds demonstrated good apatite-forming bioactivity with sustained release of Si and Sr ions. The in vitro tests demonstrated that SrCS scaffolds possessed excellent biocompatibility which in turn stimulated adhesion, proliferation, and differentiation of MSCs. In addition, the SrCS scaffolds were able to enhance MSCs synthesis of osteoprotegerin (OPG) and suppress macrophage colony-stimulating factor (M-CSF) thus disrupting normal bone homeostasis which led to enhanced bone formation over bone resorption. Implanted SrCS scaffolds were able to promote new blood vessel growth and new bone regeneration within 4 weeks after implantation in critical-sized rabbit femur defects. Therefore, it was shown that 3D printed SrCS scaffolds with specific controllable structures can be fabricated and SrCS scaffolds had enhanced mechanical property and osteogenesis behavior which makes it a suitable potential candidate for bone regeneration.


2021 ◽  
Vol 6 (1) ◽  
Author(s):  
S. Lee ◽  
L. H. Remark ◽  
A. M. Josephson ◽  
K. Leclerc ◽  
E. Muiños Lopez ◽  
...  

AbstractAdult bone regeneration is orchestrated by the precise actions of osteoprogenitor cells (OPCs). However, the mechanisms by which OPC proliferation and differentiation are linked and thereby regulated are yet to be defined. Here, we present evidence that during intramembranous bone formation OPC proliferation is controlled by Notch signaling, while differentiation is initiated by activation of canonical Wnt signaling. The temporospatial separation of Notch and Wnt signal activation during the early stages of bone regeneration suggests crosstalk between the two pathways. In vitro and in vivo manipulation of the two essential pathways demonstrate that Wnt activation leads to initiation of osteogenic differentiation and at the same time inhibits Notch signaling, which results in termination of the proliferative phase. Here, we establish canonical Wnt signaling as a key regulator that facilitates the crosstalk between OPC proliferation and differentiation during intramembranous, primary bone healing.


Biomedicines ◽  
2021 ◽  
Vol 9 (7) ◽  
pp. 712
Author(s):  
Wei-Yun Lai ◽  
Yen-Jen Chen ◽  
Alvin Kai-Xing Lee ◽  
Yen-Hong Lin ◽  
Yu-Wei Liu ◽  
...  

Worldwide, the number of bone fractures due to traumatic and accidental injuries is increasing exponentially. In fact, repairing critical large bone defects remains challenging due to a high risk of delayed union or even nonunion. Among the many bioceramics available for clinical use, calcium silicate-based (CS) bioceramics have gained popularity due to their good bioactivity and ability to stimulate cell behavior. In order to improve the shortcomings of 3D-printed ceramic scaffolds, which do not easily carry growth factors and do not provide good tissue regeneration effects, the aim of this study was to use a gelatin-coated 3D-printed magnesium-doped calcium silicate (MgCS) scaffold with genipin cross-linking for regulating degradation, improving mechanical properties, and enhancing osteogenesis behavior. In addition, we consider the effects of fibroblast growth factor-2 (FGF-2) loaded into an MgCS scaffold with and without gelatin coating. Furthermore, we cultured the human Wharton jelly-derived mesenchymal stem cells (WJMSC) on the scaffolds and observed the biocompatibility, alkaline phosphatase activity, and osteogenic-related markers. Finally, the in vivo performance was assessed using micro-CT and histological data that revealed that the hybrid bioscaffolds were able to further achieve more effective bone tissue regeneration than has been the case in the past. The above results demonstrated that this type of processing had great potential for future clinical applications and studies and can be used as a potential alternative for future bone tissue engineering research, as well as having good potential for clinical applications.


2014 ◽  
Vol 38 (1) ◽  
pp. 59-67 ◽  
Author(s):  
Xingrao Ke ◽  
Bohan Xing ◽  
Baifeng Yu ◽  
Xing Yu ◽  
Amber Majnik ◽  
...  

2014 ◽  
Vol 2 (8) ◽  
pp. 1100-1110 ◽  
Author(s):  
Ni Kong ◽  
Kaili Lin ◽  
Haiyan Li ◽  
Jiang Chang

Copper and silicon ions exhibited synergy effects in vascularization stimulation by copper-doped calcium silicate bioceramics in a HDF–HUVEC co-culture system.


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