Degradable RGD-Functionalized 3D-Printed Scaffold Promotes Osteogenesis

2021 ◽  
pp. 002203452110246
Author(s):  
P.-C. Chang ◽  
Z.-J. Lin ◽  
H.-T. Luo ◽  
C.-C. Tu ◽  
W.-C. Tai ◽  
...  

To establish an ideal microenvironment for regenerating maxillofacial defects, recent research interests have concentrated on developing scaffolds with intricate configurations and manipulating the stiffness of extracellular matrix toward osteogenesis. Herein, we propose to infuse a degradable RGD-functionalized alginate matrix (RAM) with osteoid-like stiffness, as an artificial extracellular matrix, to a rigid 3D-printed hydroxyapatite scaffold for maxillofacial regeneration. The 3D-printed hydroxyapatite scaffold was produced by microextrusion technology and showed good dimensional stability with consistent microporous detail. RAM was crosslinked by calcium sulfate to manipulate the stiffness, and its degradation was accelerated by partial oxidation using sodium periodate. The results revealed that viability of bone marrow stem cells was significantly improved on the RAM and was promoted on the oxidized RAM. In addition, the migration and osteogenic differentiation of bone marrow stem cells were promoted on the RAM with osteoid-like stiffness, specifically on the oxidized RAM. The in vivo evidence revealed that nonoxidized RAM with osteoid-like stiffness upregulated osteogenic genes but prevented ingrowth of newly formed bone, leading to limited regeneration. Oxidized RAM with osteoid-like stiffness facilitated collagen synthesis, angiogenesis, and osteogenesis and induced robust bone formation, thereby significantly promoting maxillofacial regeneration. Overall, this study supported that in the stabilized microenvironment, oxidized RAM with osteoid-like stiffness offered requisite mechanical cues for osteogenesis and an appropriate degradation profile to facilitate bone formation. Combining the 3D-printed hydroxyapatite scaffold and oxidized RAM with osteoid-like stiffness may be an advantageous approach for maxillofacial regeneration.

Biomaterials ◽  
2010 ◽  
Vol 31 (6) ◽  
pp. 1104-1113 ◽  
Author(s):  
Kyung Sook Kim ◽  
Ju Young Lee ◽  
Yun Mi Kang ◽  
E.Sle Kim ◽  
Gyeong Hae Kim ◽  
...  

Nephrology ◽  
2015 ◽  
Vol 20 (9) ◽  
pp. 591-600 ◽  
Author(s):  
Juan He ◽  
Yan Wang ◽  
Xingyan Lu ◽  
Bei Zhu ◽  
Xiaohua Pei ◽  
...  

2014 ◽  
pp. 143-162 ◽  
Author(s):  
Luke J. Mortensen ◽  
Walid Zaher ◽  
Cristina Lo Celso ◽  
Charles P. Lin

2003 ◽  
Vol 13 (Suppl 1) ◽  
pp. 58.3-58
Author(s):  
M. Jost ◽  
V. Lambert ◽  
C. Maillard ◽  
K. Bajou ◽  
C. Humblet ◽  
...  

2007 ◽  
Author(s):  
Heuy-Ching H. Wang ◽  
Harry Zwick ◽  
Peter R. Edsall ◽  
Rachel D. Cheramie ◽  
David J. Lund ◽  
...  

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 1409-1409
Author(s):  
Zhuo Wang ◽  
Junghun Jung ◽  
Magdalena Kucia ◽  
Junhui Song ◽  
Yusuke Shiozawa ◽  
...  

Abstract We previously developed an in vivo prospective assay for identification of non-cultured cells with MSC potential. Using this assay we identified a population of cells that were slowly cycling and of low density that were capable of multilineage differentiation both in vitro and in vivo (Z. Wang et al, Stem Cells. 2006 24(6):1573). Further characterization of these cells suggested that they resemble a homogenous population of rare Lin−/Sca-1+/CD45− cells that have the morphology and express several markers of undifferentiated embryonic-like stem cells. In vitro the Lin−/Sca-1+/CD45− cells may differentiate into cells from all three germ-layers (M. Kucia et al, Leukemia. 2007 21(2):297). To determine the in vivo fate of this population, we transplanted 500 or 5,000 Lin−/Sca-1+/CD45− cells from a GFP mouse into SCID mice in each group (n=3) immediately after cell sorting to evaluate tissue generation in vivo. At 4 weeks the regenerative potential of these populations was evaluated by micro-CT and histology, and cells were tracked by gross examination of the harvested tissues by fluorescent microscopy. The results showed that a large number of GFP+ cells are located in the implants, indicating that the transplanted cells maintain the ability to contribute to the generation of new tissue. Bone-like tissue was observed in the Lin−/Sca-1+/CD45− group with as low as 500-cells/implant, while 5,000 Lin−/Sca-1+/CD45− cells generated significantly larger mineralized tissue volume, which was confirmed by micro-CT. Lin−/Sca-1+/CD45+ cell only implantation did not form any mineralized tissue, however, while mixed with 2x106 whole bone morrow cells, positive mineralized tissue occurred. Whole bone marrow mixture also improve bone formation in Lin−/Sca-1+/CD45− cell implants compared the actual bone volumes measured by micro-CT. This study demonstrates that non-cultured BM-derived Lin−/Sca-1+/CD45− cells exhibit the capacity to form bone in vivo with as low as 500 cells/implant. Whole bone marrow mixtures can enhance the bone formation, presumably through the interaction of other populations cells. Based on these findings, it is proposed that non-cultured BM-derived Lin−/Sca-1+/CD45− cells are enriched osteogenic cells that can be applied to bone regeneration in vivo.


2013 ◽  
Vol 1510 ◽  
pp. 10-21 ◽  
Author(s):  
Heloisa Juliana Zabeu Rossi Costa ◽  
Ricardo Ferreira Bento ◽  
Raquel Salomone ◽  
Deborah Azzi-Nogueira ◽  
Daniela B. Zanatta ◽  
...  

2019 ◽  
Vol 3 (Supplement_1) ◽  
pp. S107-S108
Author(s):  
Dmitry Kondrikov ◽  
Ahmed Elmansi ◽  
Robert T Bragg ◽  
Tanner Mobley ◽  
Meghan mcGee-Lawrence ◽  
...  

Abstract The age-related increase of the tryptophan metabolite, kynurenine (KYN), has been associated with osteoporosis progression. Increased activity of by Indoleamine-(2,3)-dioxygenase(IDO), are responsible for the elevation of KYN levels in bone tissue. IDO activity is elevated with age and could be a promising therapeutic target forosteopenia and osteoporosis. Previously, our group has shown that the serum level of KYN is elevated with age and correlates with bone loss in vivo. Kynurenine suppress the expression and activity of chemokine CXCL12 essential for osteogenesis, bone marrow stem cells homing. Bone Marrow Stem Cells (BMSC) cultured in 1% FBS were treated with CXCL12 (100ng/ml) in the presence of saline control or the autophagic flux-inhibition agent chloroquine (CQ). CXCL12 treatment increased autophagy by upregulating the degree of LC3B-II by 20%. CXCL12 treatment also significantly increased co-localization of LC3B and LAMP-2 in serum starved cells. In the present study, we tested the theory that kynurenine plays an opposite role to CXCL12 by suppressing the autophagy cell survival pathway and by inducing apoptosis. Treatment of nutrient-deprived murine BMSCs with 10 or 100 µM of KYN suppresses autophagy in a dose dependent fashion while increasing cellular apoptosis. Treatment of BMSCs with KYN downregulated autophagic flux in BMSC preventing CQ-induced CL3B/LAMP-2 colocalization. KYN treatment prevented conversion of LC3B-I to LC3B-II in CQ-treated cells by 30 percent. At the same time, KYN treatment induces apoptosis, by increasing TUNEL-positive cells number by more than 50 percent. Additionally, KYN treatment significantly increased the levels of cleaved isoforms of PARP and caspase-3.


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