La-Doped mesoporous calcium silicate/chitosan scaffolds for bone tissue engineering

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.

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Chitosan–poly(lactide-co-glycolide) microsphere-based scaffolds for bone tissue engineering: In vitro degradation and in vivo bone regeneration studies

Acta Biomaterialia ◽

10.1016/j.actbio.2010.03.023 ◽

2010 ◽

Vol 6 (9) ◽

pp. 3457-3470 ◽

Cited By ~ 108

Author(s):

Tao Jiang ◽

Syam P. Nukavarapu ◽

Meng Deng ◽

Ehsan Jabbarzadeh ◽

Michelle D. Kofron ◽

...

Keyword(s):

Tissue Engineering ◽

Bone Tissue Engineering ◽

Bone Regeneration ◽

Bone Tissue ◽

In Vitro Degradation

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Biomechanical study of cellulose scaffolds for bone tissue engineering in vivo and in vitro.

10.1101/2021.07.07.451476 ◽

2021 ◽

Author(s):

Maxime Leblanc Latour ◽

Maryam Tarar ◽

Ryan J. Hickey ◽

Charles M. Cuerrier ◽

Isabelle Catelas ◽

...

Keyword(s):

Mechanical Properties ◽

Tissue Engineering ◽

Bone Tissue Engineering ◽

Osteogenic Differentiation ◽

Bone Tissue ◽

Cell Invasion ◽

Osteogenic Potential ◽

Load Bearing

Plant-derived cellulose biomaterials have recently been utilized in several tissue engineering applications. These naturally-derived cellulose scaffolds have been shown to be highly biocompatible in vivo, possess structural features of relevance to several tissues, and support mammalian cell invasion and proliferation. Recent work utilizing decellularized apple hypanthium tissue has shown that it possesses a pore size similar to trabecular bone and can successfully host osteogenic differentiation. In the present study, we further examined the potential of apple-derived cellulose scaffolds for bone tissue engineering (BTE) and analyzed their mechanical properties in vitro and in vivo. MC3T3-E1 pre-osteoblasts were seeded in cellulose scaffolds. Following chemically-induced osteogenic differentiation, scaffolds were evaluated for mineralization and for their mechanical properties. Alkaline phosphatase and Alizarin Red staining confirmed the osteogenic potential of the scaffolds. Histological analysis of the constructs revealed cell invasion and mineralization throughout the constructs. Furthermore, scanning electron microscopy demonstrated the presence of mineral aggregates on the scaffolds after culture in differentiation medium, and energy-dispersive spectroscopy confirmed the presence of phosphate and calcium. However, although the Young′s modulus significantly increased after cell differentiation, it remained lower than that of healthy bone tissue. Interestingly, mechanical assessment of acellular scaffolds implanted in rat calvaria defects for 8 weeks revealed that the force required to push out the scaffolds from the surrounding bone was similar to that of native calvarial bone. In addition, cell infiltration and extracellular matrix deposition were visible within the implanted scaffolds. Overall, our results confirm that plant-derived cellulose is a promising candidate for BTE applications. However, the discrepancy in mechanical properties between the mineralized scaffolds and healthy bone tissue may limit their use to low load-bearing applications. Further structural re-engineering and optimization to improve the mechanical properties may be required for load-bearing applications.

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Extracellular matrix-inspired BMP-2-delivering biodegradable fibrous particles for bone tissue engineering

Journal of Materials Chemistry B ◽

10.1039/c5tb01310k ◽

2015 ◽

Vol 3 (42) ◽

pp. 8375-8382 ◽

Cited By ~ 18

Author(s):

Young Min Shin ◽

Wan-Geun La ◽

Min Suk Lee ◽

Hee Seok Yang ◽

Youn-Mook Lim

Keyword(s):

Tissue Engineering ◽

Extracellular Matrix ◽

Bone Tissue Engineering ◽

Osteogenic Differentiation ◽

Bone Tissue ◽

Bone Defect

A heparin conjugated fibrous particle resembling the structure of an extracellular matrix was developed. The BMP-2 loaded particles promoted osteogenic differentiation and healing of a bone defect, in vitro and in vivo.

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

PeerJ ◽

10.7717/peerj.2040 ◽

2016 ◽

Vol 4 ◽

pp. e2040 ◽

Cited By ~ 22

Author(s):

Hui Xie ◽

Zhenxing Wang ◽

Liming Zhang ◽

Qian Lei ◽

Aiqi Zhao ◽

...

Keyword(s):

Tissue Engineering ◽

Bone Tissue Engineering ◽

Bone Regeneration ◽

Bone Tissue ◽

Umbilical Vein ◽

Composite Graft ◽

Electron Microscopic ◽

Engineering Applications

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.

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Comparing bone tissue engineering efficacy of HDPSCs, HBMSCs on 3D biomimetic ABM-P-15 scaffolds in vitro and in vivo

Cytotechnology ◽

10.1007/s10616-020-00414-7 ◽

2020 ◽

Vol 72 (5) ◽

pp. 715-730 ◽

Cited By ~ 1

Author(s):

Yamuna Mohanram ◽

Jingying Zhang ◽

Eleftherios Tsiridis ◽

Xuebin B. Yang

Keyword(s):

Tissue Engineering ◽

Stem Cells ◽

Bone Tissue Engineering ◽

Bone Regeneration ◽

Bone Tissue ◽

Proliferation Rate ◽

Osteogenic Potential ◽

In Vivo Model

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.

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Graphene and its Derivatives for Bone Tissue Engineering: In Vitro and In Vivo Evaluation of Graphene-Based Scaffolds, Membranes and Coatings

Frontiers in Bioengineering and Biotechnology ◽

10.3389/fbioe.2021.734688 ◽

2021 ◽

Vol 9 ◽

Author(s):

Junyao Cheng ◽

Jianheng Liu ◽

Bing Wu ◽

Zhongyang Liu ◽

Ming Li ◽

...

Keyword(s):

Tissue Engineering ◽

Regenerative Medicine ◽

Bone Tissue Engineering ◽

Bone Regeneration ◽

Bone Tissue ◽

Bone Grafts ◽

Biological Properties ◽

In Vivo Evaluation

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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Aldo-keto reductase family 1 member C1 regulates the osteogenic differentiation of human ASCs by targeting the progesterone receptor

Stem Cell Research & Therapy ◽

10.1186/s13287-021-02425-3 ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Xuenan Liu ◽

Xiaomin Lian ◽

Xuejiao Liu ◽

Yangge Du ◽

Yuan Zhu ◽

...

Keyword(s):

Tissue Engineering ◽

Progesterone Receptor ◽

Bone Tissue Engineering ◽

Osteogenic Differentiation ◽

Bone Tissue ◽

Adipogenic Differentiation ◽

Molecular Target ◽

Negative Regulator

Abstract Background As a promising way to repair bone defect, bone tissue engineering has attracted a lot of attentions from researchers in recent years. Searching for new molecular target to modify the seed cells and enhance their osteogenesis capacity is one of the hot topics in this field. As a member of aldo-keto reductase family, aldo-keto reductase family 1 member C1 (AKR1C1) is reported to associate with various tumors. However, whether AKR1C1 takes part in regulating differentiation of adipose-derived mesenchymal stromal/stem cells (ASCs) and its relationship with progesterone receptor (PGR) remain unclear. Methods Lost-and-gain-of-function experiments were performed using knockdown and overexpression of AKR1C1 to identify its role in regulating osteogenic and adipogenic differentiation of hASCs in vitro. Heterotypic bone and adipose tissue formation assay in nude mice were used to conduct the in vivo experiment. Plasmid and siRNA of PGR, as well as western blot, were used to clarify the mechanism AKR1C1 regulating osteogenesis. Results Our results demonstrated that AKR1C1 acted as a negative regulator of osteogenesis and a positive regulator of adipogenesis of hASCs via its enzyme activity both in vitro and in vivo. Mechanistically, PGR mediated the regulation of AKR1C1 on osteogenesis. Conclusions Collectively, our study suggested that AKR1C1 could serve as a regulator of osteogenic differentiation via targeting PGR and be used as a new molecular target for ASCs modification in bone tissue engineering.

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Gelatin methacrylate hydrogel scaffold carrying resveratrol-loaded solid lipid nanoparticles for enhancement of osteogenic differentiation of BMSCs and effective bone regeneration

Regenerative Biomaterials ◽

10.1093/rb/rbab044 ◽

2021 ◽

Author(s):

Bangguo Wei ◽

Wenrui Wang ◽

Xiangyu Liu ◽

Chenxi Xu ◽

Yanan Wang ◽

...

Keyword(s):

Tissue Engineering ◽

Bone Tissue Engineering ◽

Bone Regeneration ◽

Osteogenic Differentiation ◽

Bone Tissue ◽

Solid Lipid Nanoparticles ◽

Lipid Nanoparticles ◽

Tumour Resection ◽

Solid Lipid

Abstract Critical-sized bone defects caused by traumatic fractures, tumour resection, and congenital malformation are unlikely to heal spontaneously. Bone tissue engineering is a promising strategy aimed at developing in vitro replacements for bone transplantation and overcoming the limitations of natural bone grafts. In this study, we developed an innovative bone engineering scaffold based on gelatin methacrylate (GelMA) hydrogel, obtained via a two-step procedure: first, solid lipid nanoparticles (SLNs) were loaded with resveratrol (Res), a drug that can promote osteogenic differentiation and bone formation; these particles were then encapsulated at different concentrations (0.01%, 0.02%, 0.04%, and 0.08%) in GelMA to obtain the final Res-SLNs/GelMA scaffolds. The effects of these scaffolds on osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) and bone regeneration in rat cranial defects were evaluated using various characterization assays. Our in vitro and in vivo investigations demonstrated that the different Res-SLNs/GelMA scaffolds improved the osteogenic differentiation of BMSCs, with the ideally slow and steady release of Res; the optimal scaffold was 0.02 Res-SLNs/GelMA. Therefore, the 0.02 Res-SLNs/GelMA hydrogel is an appropriate release system for Res with good biocompatibility, osteoconduction, and osteoinduction, thereby showing potential for application in bone tissue engineering.

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