scholarly journals The Delivery of Extracellular Vesicles Loaded in Biomaterial Scaffolds for Bone Regeneration

Author(s):  
Hui-Chun Yan ◽  
Ting-Ting Yu ◽  
Jing Li ◽  
Yi-Qiang Qiao ◽  
Lin-Chuan Wang ◽  
...  
2020 ◽  
Author(s):  
Xijiao Yu ◽  
Yuxuan Wang ◽  
Xiao-Liang Liu ◽  
Degang Yu ◽  
Shanyong Zhang

Abstract Background: Mesoporous hydroxylapatite (MHAP) could play an important role in bone regeneration, and UA (Ursolic acid) also promote the osteogenic differentiation. Accordingly, we developed the UA loaded MHAP scaffolds to cure bone defects. In vitro, we synthesize biomaterial scaffolds. By SEM, XRD, EDS and FTIR, we test the performance of the hybrid scaffolds. By drug release, ALP staining, Alizarin red staining, and Western blotting, we test the osteo-inductive properties of scaffold materials. In vivo, We verify bone regeneration through a rat skull defect model.Results: The MHAP is a rod-shaped structure with a length of 100~300nm and a diameter of 40~60nm. The critical structure gives the micro scaffold a property of control release due to the pore sizes of 1.6~4.3 nm in hydroxyapatite and the hydrogen bonding between the scaffolds and UA drugs. The released UA drugs could notably promote the expression of osteogenic-related genes (COL1, ALP, OPG) and osteogenic-related proteins (BMP-2, RUNX2 and COL1). Both the images of μCT and the results of double fluorochrome labelling demonstrated that therapeutic scaffolds promoted the bone regeneration. We obtained the similar results through immunohistochemistry. Conclusions: The MHAP-CS-UA scaffolds have good osteo-inductivity and bone regeneration. And they will be the novel and promising candidates to cure the bone disease.


2009 ◽  
Vol 89 (1) ◽  
pp. 77-81 ◽  
Author(s):  
W.-W. Hu ◽  
B.B. Ward ◽  
Z. Wang ◽  
P.H. Krebsbach

Because bone reconstruction in irradiated sites is less than ideal, we applied a regenerative gene therapy method in which a cell-signaling virus was localized to biomaterial scaffolds to regenerate wounds compromised by radiation therapy. Critical-sized defects were created in rat calvariae previously treated with radiation. Gelatin scaffolds containing lyophilized adenovirus encoding BMP-2 (AdBMP-2) or freely suspended AdBMP-2 were transplanted. Lyophilized AdBMP-2 significantly improved bone quality and quantity over free AdBMP-2. Bone mineral density was reduced after radiotherapy. Histological analyses demonstrated that radiation damage led to less bone regeneration. The woven bone and immature marrow formed in the radiated defects indicated that irradiation retarded normal bone development. Finally, we stored the scaffolds with lyophilized AdBMP-2 at −80°C to determine adenovirus stability. Micro-CT quantification demonstrated no significant differences between bone regeneration treated with lyophilized AdBMP-2 before and after storage, suggesting that virus-loaded scaffolds may be convenient for application as pre-made constructs.


Author(s):  
Kenny Man ◽  
Mathieu Y. Brunet ◽  
Sophie Louth ◽  
Thomas E. Robinson ◽  
Maria Fernandez-Rhodes ◽  
...  

Extracellular Vesicles (EVs) are considered promising nanoscale therapeutics for bone regeneration. To date, EVs are typically procured from cells on 2D tissue culture plastic, an artificial environment that limits cell growth and does not replicate in situ biochemical or biophysical conditions. This study investigated the potential of 3D printed titanium scaffolds coated with hydroxyapatite to promote the therapeutic efficacy of osteoblast-derived EVs. Ti6Al4V titanium scaffolds with different pore sizes (500 and 1000 µm) and shapes (square and triangle) were fabricated by selective laser melting. A bone-mimetic nano-needle hydroxyapatite (nnHA) coating was then applied. EVs were procured from scaffold-cultured osteoblasts over 2 weeks and vesicle concentration was determined using the CD63 ELISA. Osteogenic differentiation of human bone marrow stromal cells (hBMSCs) following treatment with primed EVs was evaluated by assessing alkaline phosphatase activity, collagen production and calcium deposition. Triangle pore scaffolds significantly increased osteoblast mineralisation (1.5-fold) when compared to square architectures (P ≤ 0.001). Interestingly, EV yield was also significantly enhanced on these higher permeability structures (P ≤ 0.001), in particular (2.2-fold) for the larger pore structures (1000 µm). Furthermore osteoblast-derived EVs isolated from triangular pore scaffolds significantly increased hBMSCs mineralisation when compared to EVs acquired from square pore scaffolds (1.7-fold) and 2D culture (2.2-fold) (P ≤ 0.001). Coating with nnHA significantly improved osteoblast mineralisation (>2.6-fold) and EV production (4.5-fold) when compared to uncoated scaffolds (P ≤ 0.001). Together, these findings demonstrate the potential of harnessing bone-mimetic culture platforms to enhance the production of pro-regenerative EVs as an acellular tool for bone repair.


2021 ◽  
Vol Publish Ahead of Print ◽  
Author(s):  
Zeynep Akdeniz-Dogan ◽  
Samet Sendur ◽  
Betul Karademir-Yilmaz ◽  
Onur Bugdayci ◽  
Ozlem T. Kaya ◽  
...  

Materials ◽  
2019 ◽  
Vol 12 (14) ◽  
pp. 2296 ◽  
Author(s):  
Alexandra Roi ◽  
Lavinia Cosmina Ardelean ◽  
Ciprian Ioan Roi ◽  
Eugen-Radu Boia ◽  
Simina Boia ◽  
...  

The advancements made in biomaterials have an important impact on oral tissue engineering, especially on the bone regeneration process. Currently known as the gold standard in bone regeneration, grafting procedures can sometimes be successfully replaced by a biomaterial scaffold with proper characteristics. Whether natural or synthetic polymers, biomaterials can serve as potential scaffolds with major influences on cell adhesion, proliferation and differentiation. Continuous research has enabled the development of scaffolds that can be specifically designed to replace the targeted tissue through changes in their surface characteristics and the addition of growth factors and biomolecules. The progress in tissue engineering is incontestable and research shows promising contributions to the further development of this field. The present review aims to outline the progress in oral tissue engineering, the advantages of biomaterial scaffolds, their direct implication in the osteogenic process and future research directions.


2020 ◽  
Vol 10 (7) ◽  
pp. 2336
Author(s):  
Alessandra Giuliani ◽  
Gabriela Sena ◽  
Giuliana Tromba ◽  
Emanuela Mazzon ◽  
Antonella Fontana ◽  
...  

Tissue engineering has been shown to offer promising approaches for bone regeneration, mostly based on replacement with biomaterials that provide specific environments and support for bone growth. In this context, we previously showed that mesenchymal stem cells (MSCs) and their derivatives, such as conditioned medium (CM) and extracellular vesicles (EV), when seeded on collagen membranes (COL) or polylactide (PLA) biomaterials, are able to favor bone tissue regeneration, especially evidenced in animal model calvary defects. In the present study, we investigated whether the enrichment of a rat calvary defect site with CM, EVs and polyethylenimine (PEI)-engineered EVs could substantially modify the bone remodeling kinetics during defect healing, as these products were reported to favor bone regeneration. In particular, we focused the study, performed by synchrotron radiation-based high-resolution tomography, on the analysis of the bone mass density distribution. We proved that the enrichment of a defect site with CM, EVs and PEI-EVs substantially modifies, often accelerating, bone remodeling kinetics and the related mineralization process during defect healing. Moreover, different biomaterials (COL or PLA) in combination with stem cells of different origin (namely, human periodontal ligament stem cells-hPDLSCs and human gingival mesenchymal stem cells-hGMSCs) and their own CM, EVs and PEI-EVs products were shown to exhibit different mineralization kinetics.


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