scholarly journals Development of an angiogenesis-promoting microvesicle-alginate-polycaprolactone composite graft for bone tissue engineering applications

PeerJ ◽  
2016 ◽  
Vol 4 ◽  
pp. e2040 ◽  
Author(s):  
Hui Xie ◽  
Zhenxing Wang ◽  
Liming Zhang ◽  
Qian Lei ◽  
Aiqi Zhao ◽  
...  

One of the major challenges of bone tissue engineering applications is to construct a fully vascularized implant that can adapt to hypoxic environments in vivo. The incorporation of proangiogenic factors into scaffolds is a widely accepted method of achieving this goal. Recently, the proangiogenic potential of mesenchymal stem cell-derived microvesicles (MSC-MVs) has been confirmed in several studies. In the present study, we incorporated MSC-MVs into alginate-polycaprolactone (PCL) constructs that had previously been developed for bone tissue engineering applications, with the aim of promoting angiogenesis and bone regeneration. MSC-MVs were first isolated from the supernatant of rat bone marrow-derived MSCs and characterized by scanning electron microscopic, confocal microscopic, and flow cytometric analyses. The proangiogenic potential of MSC-MVs was demonstrated by the stimulation of tube formation of human umbilical vein endothelial cellsin vitro. MSC-MVs and osteodifferentiated MSCs were then encapsulated with alginate and seeded onto porous three-dimensional printed PCL scaffolds. When combined with osteodifferentiated MSCs, the MV-alginate-PCL constructs enhanced vessel formation and tissue-engineered bone regeneration in a nude mouse subcutaneous bone formation model, as demonstrated by micro-computed tomographic, histological, and immunohistochemical analyses. This MV-alginate-PCL construct may offer a novel, proangiogenic, and cost-effective option for bone tissue engineering.

Materials ◽  
2014 ◽  
Vol 7 (3) ◽  
pp. 1957-1974 ◽  
Author(s):  
Ulrike Rottensteiner ◽  
Bapi Sarker ◽  
Dominik Heusinger ◽  
Diana Dafinova ◽  
Subha Rath ◽  
...  

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Jie Bai ◽  
Lijun Li ◽  
Ni Kou ◽  
Yuwen Bai ◽  
Yaoyang Zhang ◽  
...  

Abstract Background Bone tissue engineering is a new concept bringing hope for the repair of large bone defects, which remains a major clinical challenge. The formation of vascularized bone is key for bone tissue engineering. Growth of specialized blood vessels termed type H is associated with bone formation. In vivo and in vitro studies have shown that low level laser therapy (LLLT) promotes angiogenesis, fracture healing, and osteogenic differentiation of stem cells by increasing reactive oxygen species (ROS). However, whether LLLT can couple angiogenesis and osteogenesis, and the underlying mechanisms during bone formation, remains largely unknown. Methods Mouse bone marrow mesenchymal stem cells (BMSCs) combined with biphasic calcium phosphate (BCP) grafts were implanted into C57BL/6 mice to evaluate the effects of LLLT on the specialized vessel subtypes and bone regeneration in vivo. Furthermore, human BMSCs and human umbilical vein endothelial cells (HUVECs) were co-cultured in vitro. The effects of LLLT on cell proliferation, angiogenesis, and osteogenesis were assessed. Results LLLT promoted the formation of blood vessels, collagen fibers, and bone tissue and also increased CD31hiEMCNhi-expressing type H vessels in mBMSC/BCP grafts implanted in mice. LLLT significantly increased both osteogenesis and angiogenesis, as well as related gene expression (HIF-1α, VEGF, TGF-β) of grafts in vivo and of co-cultured BMSCs/HUVECs in vitro. An increase or decrease of ROS induced by H2O2 or Vitamin C, respectively, resulted in an increase or decrease of HIF-1α, and a subsequent increase and decrease of VEGF and TGF-β in the co-culture system. The ROS accumulation induced by LLLT in the co-culture system was significantly decreased when HIF-1α was inhibited with DMBPA and was followed by decreased expression of VEGF and TGF-β. Conclusions LLLT enhanced vascularized bone regeneration by coupling angiogenesis and osteogenesis. ROS/HIF-1α was necessary for these effects of LLLT. LLLT triggered a ROS-dependent increase of HIF-1α, VEGF, and TGF-β and resulted in subsequent formation of type H vessels and osteogenic differentiation of mesenchymal stem cells. As ROS also was a target of HIF-1α, there may be a positive feedback loop between ROS and HIF-1α, which further amplified HIF-1α induction via the LLLT-mediated ROS increase. This study provided new insight into the effects of LLLT on vascularization and bone regeneration in bone tissue engineering.


2010 ◽  
Vol 6 (9) ◽  
pp. 3457-3470 ◽  
Author(s):  
Tao Jiang ◽  
Syam P. Nukavarapu ◽  
Meng Deng ◽  
Ehsan Jabbarzadeh ◽  
Michelle D. Kofron ◽  
...  

Author(s):  
Maxime Leblanc Latour ◽  
Maryam Tarar ◽  
Ryan J. Hickey ◽  
Charles M. Cuerrier ◽  
Isabelle Catelas ◽  
...  

AbstractPlant-derived cellulose biomaterials have recently been utilized in several tissue engineering applications. Naturally-derived cellulose scaffolds have been shown to be highly biocompatible in vivo, possess structural features of relevance to several tissues, as well as support mammalian cell invasion and proliferation. Recent work utilizing decellularized apple hypanthium tissue has shown that it possesses a pore size and properties similar to trabecular bone. In the present study, we examined the potential of apple-derived cellulose scaffolds for bone tissue engineering (BTE). Confocal microscopy revealed that the scaffolds had a suitable pore size for BTE applications. To analyze their in vitro mineralization potential, MC3T3-E1 pre-osteoblasts were seeded in either bare cellulose scaffolds or in composite scaffolds composed of cellulose and collagen I. Following chemically-induced differentiation, scaffolds were mechanically tested and evaluated for mineralization. The Young’s modulus of both types of scaffolds significantly increased after cell differentiation. Alkaline phosphatase and Alizarin Red staining further highlighted the osteogenic potential of the scaffolds. Histological sectioning of the constructs revealed complete invasion by the cells and mineralization throughout the entire constructs. Finally, scanning electron microscopy demonstrated the presence of mineral aggregates deposited on the scaffolds after differentiation, and energy-dispersive spectroscopy confirmed the presence of phosphate and calcium. In summary, our results indicate that plant-derived cellulose is a promising scaffold candidate for bone tissue engineering applications.


2019 ◽  
Vol 7 (4) ◽  
pp. 1565-1573 ◽  
Author(s):  
Xiao-Yuan Peng ◽  
Min Hu ◽  
Fang Liao ◽  
Fan Yang ◽  
Qin-Fei Ke ◽  
...  

La-MCS/CTS scaffolds promoted the proliferation and osteogenic differentiation of rBMSCs in vitro and bone regeneration in vivo.


2020 ◽  
Vol 72 (5) ◽  
pp. 715-730 ◽  
Author(s):  
Yamuna Mohanram ◽  
Jingying Zhang ◽  
Eleftherios Tsiridis ◽  
Xuebin B. Yang

Abstract Human bone marrow mesenchymal stem cells (HBMSCs) has been the gold standard for bone regeneration. However, the low proliferation rate and long doubling time limited its clinical applications. This study aims to compare the bone tissue engineering efficacy of human dental pulp stem cells (HDPSCs) with HBMSCs in 2D, and 3D anorganic bone mineral (ABM) coated with a biomimetic collagen peptide (ABM-P-15) for improving bone-forming speed and efficacy in vitro and in vivo. The multipotential of both HDPSCs and HBMSCs have been compared in vitro. The bone formation of HDPSCs on ABM-P-15 was tested using in vivo model. The osteogenic potential of the cells was confirmed by alkaline phosphatase (ALP) and immunohistological staining for osteogenic markers. Enhanced ALP, collagen, lipid droplet, or glycosaminoglycans production were visible in HDPSCs and HBMSCs after osteogenic, adipogenic and chondrogenic induction. HDPSC showed stronger ALP staining compared to HBMSCs. Confocal images showed more viable HDPSCs on both ABM-P-15 and ABM scaffolds compared to HBMSCs on similar scaffolds. ABM-P-15 enhanced cell attachment/spreading/bridging formation on ABM-P-15 scaffolds and significantly increased quantitative ALP specific activities of the HDPSCs and HBMSCs. After 8 weeks in vivo implantation in diffusion chamber model, the HDPSCs on ABM-P-15 scaffolds showed extensive high organised collagenous matrix formation that was positive for COL-I and OCN compared to ABM alone. In conclusion, the HDPSCs have a higher proliferation rate and better osteogenic capacity, which indicated the potential of combining HDPSCs with ABM-P-15 scaffolds for improving bone regeneration speed and efficacy.


Author(s):  
Eamon J. Sheehy ◽  
Tatiana Vinardell ◽  
Conor T. Buckley ◽  
Daniel J. Kelly

Tissue engineering applications aim to replace or regenerate damaged tissues through a combination of cells, three-dimensional scaffolds, and signaling molecules [1]. The endochondral approach to bone tissue engineering [2], which involves remodeling of an intermittent hypertrophic cartilaginous template, may be superior to the traditional intramembranous approach. Naturally derived hydrogels have been used extensively in tissue engineering applications [3]. Mesenchymal stem cell (MSC) seeded hydrogels may be a particularly powerful tool in scaling-up engineered endochondral bone grafts as the low oxygen conditions that develop within large constructs enhance in vitro chondrogenic differentiation and functional development [4]. A key requirement however, is that the hydrogel must allow for remodeling of the engineered hypertrophic cartilage into bone and also facilitate vascularization of the graft. The first objective of this study was to compare the capacity of different naturally derived hydrogels (alginate, chitosan, and fibrin) to generate in vivo endochondral bone. The secondary objective was to investigate the possibility of engineering a ‘scaled-up’ anatomically accurate distal phalange as a paradigm for whole bone tissue engineering.


ACS Omega ◽  
2021 ◽  
Author(s):  
Ganesan Priya ◽  
Balaraman Madhan ◽  
Uttamchand Narendrakumar ◽  
Rayadurgam Venkata Suresh Kumar ◽  
Inderchand Manjubala

Author(s):  
Junyao Cheng ◽  
Jianheng Liu ◽  
Bing Wu ◽  
Zhongyang Liu ◽  
Ming Li ◽  
...  

Bone regeneration or replacement has been proved to be one of the most effective methods available for the treatment of bone defects caused by different musculoskeletal disorders. However, the great contradiction between the large demand for clinical therapies and the insufficiency and deficiency of natural bone grafts has led to an urgent need for the development of synthetic bone graft substitutes. Bone tissue engineering has shown great potential in the construction of desired bone grafts, despite the many challenges that remain to be faced before safe and reliable clinical applications can be achieved. Graphene, with outstanding physical, chemical and biological properties, is considered a highly promising material for ideal bone regeneration and has attracted broad attention. In this review, we provide an introduction to the properties of graphene and its derivatives. In addition, based on the analysis of bone regeneration processes, interesting findings of graphene-based materials in bone regenerative medicine are analyzed, with special emphasis on their applications as scaffolds, membranes, and coatings in bone tissue engineering. Finally, the advantages, challenges, and future prospects of their application in bone regenerative medicine are discussed.


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