scholarly journals Disturbed Expression of EphB4, but Not EphrinB2, Inhibited Bone Regeneration in an In Vivo Inflammatory Microenvironment

2016 ◽  
Vol 2016 ◽  
pp. 1-13 ◽  
Author(s):  
Li-Li Shen ◽  
Li-Xia Zhang ◽  
Li-Mei Wang ◽  
Rong-Jing Zhou ◽  
Cheng-Zhe Yang ◽  
...  
Keyword(s):  
Bone Regeneration ◽  
Bone Tissue ◽  
Bone Defects ◽  
Marker Genes ◽  
Ctrl Group ◽  
Expression Levels ◽  
Inflammatory Microenvironment ◽  
Chemical Structures ◽  
Significant Difference

The important role of ephrinB2-EphB4 signaling pathway in bone remodeling has been well established. However, it is still unclear whether this bidirectional signaling also has effects on the regenerative processes of bone defects created in an inflammatory microenvironment. In this study, an experimental animal model of bone defects treated with lentiviruses was prepared and an inflammatory microenvironment was established. Expression levels of bone marker genes were monitored in the newly formed bone tissue using quantitative reverse transcriptase polymerase chain reaction and western blot. Immunohistochemical (IHC) staining and histomorphometric analysis were also performed to evaluate bone healing processes. Compared with the pLenti6.3-ctrl group, the pLenti6.3-ephb4siRNA group exhibited lower expression levels of bone formation marker genes and a higher level of NFATc1 in the new bone tissue. In addition, the newly formed bone was thinner and the number of giant osteoclasts was higher in the pLenti6.3-ephb4siRNA group than that in the pLenti6.3-ctrl group. In contrast, there was no significant difference between the pLenti6.3-efnb2siRNA group and the pLenti6.3-ctrl group. In conclusion, EphB4 plays an irreplaceable role in bone regeneration in an inflammatory microenvironment, whereas the functional loss of ephrinB2 can be effectively compensated, most possibly by other ephrins with similar chemical structures.

scholarly journals Cellularizing hydrogel-based scaffolds to repair bone tissue: How to create a physiologically relevant micro-environment?

2017 ◽  
Vol 8 ◽  
pp. 204173141771207 ◽  
Author(s):  
Mathieu Maisani ◽  
Daniele Pezzoli ◽  
Olivier Chassande ◽  
Diego Mantovani
Keyword(s):  
Bone Regeneration ◽  
Bone Tissue ◽  
Bone Repair ◽  
Critical Issue ◽  
Bone Defects ◽  
Bone Tissue Regeneration ◽  
Differentiation Potential ◽  
Promising Alternative

Tissue engineering is a promising alternative to autografts or allografts for the regeneration of large bone defects. Cell-free biomaterials with different degrees of sophistication can be used for several therapeutic indications, to stimulate bone repair by the host tissue. However, when osteoprogenitors are not available in the damaged tissue, exogenous cells with an osteoblast differentiation potential must be provided. These cells should have the capacity to colonize the defect and to participate in the building of new bone tissue. To achieve this goal, cells must survive, remain in the defect site, eventually proliferate, and differentiate into mature osteoblasts. A critical issue for these engrafted cells is to be fed by oxygen and nutrients: the transient absence of a vascular network upon implantation is a major challenge for cells to survive in the site of implantation, and different strategies can be followed to promote cell survival under poor oxygen and nutrient supply and to promote rapid vascularization of the defect area. These strategies involve the use of scaffolds designed to create the appropriate micro-environment for cells to survive, proliferate, and differentiate in vitro and in vivo. Hydrogels are an eclectic class of materials that can be easily cellularized and provide effective, minimally invasive approaches to fill bone defects and favor bone tissue regeneration. Furthermore, by playing on their composition and processing, it is possible to obtain biocompatible systems with adequate chemical, biological, and mechanical properties. However, only a good combination of scaffold and cells, possibly with the aid of incorporated growth factors, can lead to successful results in bone regeneration. This review presents the strategies used to design cellularized hydrogel-based systems for bone regeneration, identifying the key parameters of the many different micro-environments created within hydrogels.

scholarly journals The Co-Culture of ASCs and EPCs Promotes Vascularized Bone Regeneration in Critical-Sized Bone Defects of Cranial Bone in Rats

2020 ◽  
Author(s):  
yuanjia he ◽  
Shuang Lin ◽  
Qiang Ao ◽  
Xiaoning He
Keyword(s):  
Bone Regeneration ◽  
Bone Tissue ◽  
Bone Defect ◽  
Culture System ◽  
Donor Site ◽  
Bone Defects ◽  
Cranial Bone ◽  
Vascularized Bone

Abstract Background: The repair of critical-sized bone defect represents a challenging problem in bone tissue engineering. To address the most important problem in bone defect repair, namely insufficient blood supply, this study aimed to find a method that can promote the formation of vascularized bone tissue.Method The phenotypes of ASCs and EPCs were identified respectively, and ASCs/EPCs were co-cultured in vitro to detect the expression of osteogenic and angiogenic genes. Furthermore, the co-culture system combined with scaffold material was used to repair the critical-sized bone defects of the cranial bone in rats.Results The co-culture of ASCs/EPCs could increase osteogenesis and angiogenesis-related gene expression in vitro. The results of in vivo animal experiments demonstrated that the ASCs/EPCs group could promote bone regeneration and vascularization in the meantime and, then significantly accelerate the repair of critical-sized bone defects.Conclusion It is feasible to replace traditional single seed cells with ASCs/EPCs co-culture system for vascularized bone regeneration. This system could ultimately enable clinicians to better repair the defect of craniofacial bone and avoid donor site morbidity.

scholarly journals The Co-Culture of ASCs and EPCs Promotes Vascularized Bone Regeneration in Critical-Sized Bone Defects of Cranial Bone in Rats

2020 ◽  
Author(s):  
yuanjia he ◽  
Shuang Lin ◽  
Qiang Ao ◽  
Xiaoning He
Keyword(s):  
Bone Regeneration ◽  
Bone Tissue ◽  
Bone Defect ◽  
Culture System ◽  
Donor Site ◽  
Bone Defects ◽  
Cranial Bone ◽  
Vascularized Bone

Abstract Background: The repair of critical-sized bone defect represents a challenging problem in bone tissue engineering. To address the most important problem in bone defect repair, namely insufficient blood supply, this study aimed to find a method that can promote the formation of vascularized bone tissue.Method The phenotypes of ASCs and EPCs were identified respectively, and ASCs/EPCs were co-cultured in vitro to detect the expression of osteogenic and angiogenic genes. Furthermore, the co-culture system combined with scaffold material was used to repair the critical-sized bone defects of the cranial bone in rats.Results The co-culture of ASCs/EPCs could increase osteogenesis and angiogenesis-related gene expression in vitro. The results of in vivo animal experiments demonstrated that the ASCs/EPCs group could promote bone regeneration and vascularization in the meantime and, then significantly accelerate the repair of critical-sized bone defects.Conclusion It is feasible to replace traditional single seed cells with ASCs/EPCs co-culture system for vascularized bone regeneration. This system could ultimately enable clinicians to better repair the defect of craniofacial bone and avoid donor site morbidity.

scholarly journals Guided bone regeneration of chronic non‐contained bone defects using a volume stable porous block TiO2 scaffold: An experimental in vivo study

2021 ◽  
Author(s):  
Minh Khai Le Thieu ◽  
Håvard Jostein Haugen ◽  
Javier Sanz‐Esporrin ◽  
Mariano Sanz ◽  
Ståle Petter Lyngstadaas ◽  
...  
Keyword(s):  
Bone Regeneration ◽  
Bone Defects ◽  
Guided Bone Regeneration ◽  
In Vivo Study ◽  
Porous Block

scholarly journals Longitudinal in vivo evaluation of bone regeneration by combined measurement of multi-pinhole SPECT and micro-CT for tissue engineering

2015 ◽  
Vol 5 (1) ◽  
Author(s):  
Philipp S. Lienemann ◽  
Stéphanie Metzger ◽  
Anna-Sofia Kiveliö ◽  
Alain Blanc ◽  
Panagiota Papageorgiou ◽  
...  
Keyword(s):  
Computed Tomography ◽  
High Resolution ◽  
Bone Formation ◽  
Bone Regeneration ◽  
Bone Defects ◽  
Histological Evaluation ◽  
Biological Processes ◽  
Micro Ct ◽  
Pinhole Spect

Abstract Over the last decades, great strides were made in the development of novel implants for the treatment of bone defects. The increasing versatility and complexity of these implant designs request for concurrent advances in means to assess in vivo the course of induced bone formation in preclinical models. Since its discovery, micro-computed tomography (micro-CT) has excelled as powerful high-resolution technique for non-invasive assessment of newly formed bone tissue. However, micro-CT fails to provide spatiotemporal information on biological processes ongoing during bone regeneration. Conversely, due to the versatile applicability and cost-effectiveness, single photon emission computed tomography (SPECT) would be an ideal technique for assessing such biological processes with high sensitivity and for nuclear imaging comparably high resolution (<1 mm). Herein, we employ modular designed poly(ethylene glycol)-based hydrogels that release bone morphogenetic protein to guide the healing of critical sized calvarial bone defects. By combined in vivo longitudinal multi-pinhole SPECT and micro-CT evaluations we determine the spatiotemporal course of bone formation and remodeling within this synthetic hydrogel implant. End point evaluations by high resolution micro-CT and histological evaluation confirm the value of this approach to follow and optimize bone-inducing biomaterials.

scholarly journals Preliminary in Vivo Evaluation of Bone Healing in Critical Size Bone Defects Implanted with an Injectable Calcium Phosphate Bone Cement (Osteopaste)

2017 ◽  
Vol 16 (1) ◽  
Author(s):  
Che Nor Zarida Che Seman ◽  
Zamzuri Zakaria ◽  
Zunariah Buyong ◽  
Mohd Shukrimi Awang ◽  
Ahmad Razali Md Ralib @ Md Raghib
Keyword(s):  
Calcium Phosphate ◽  
Bone Cement ◽  
Bone Tissue ◽  
Bone Repair ◽  
Critical Size ◽  
Healing Process ◽  
Bone Defects ◽  
Calcium Phosphate Bone Cement ◽  
Rabbit Tibia

Introduction: A novel injectable calcium phosphate bone cement (osteopaste) has been developed. Its potential application in orthopaedics as a filler of bone defects has been studied. The biomaterial was composed of tetra-calcium phosphate (TTCP) and tricalcium phosphate (TCP) powder. The aim of the present study was to evaluate the healing process of osteopaste in rabbit tibia. Materials and method: The implantation procedure was carried out on thirty-nine of New Zealand white rabbits. The in vivo bone formation was investigated by either implanting the Osteopaste, Jectos or MIIG – X3 into a critical size defect (CSD) model in the proximal tibial metaphysis. CSD without treatment served as negative control. After 1 day, 6 and 12 weeks, the rabbits were euthanized, the bone were harvested and subjected for analysis. Results: Radiological images and histological sections revealed integration of implants with bone tissue with no signs of graft rejection. There was direct contact between osteopaste material and host bone. The new bone was seen bridging the defect. Conclusion: The result showed that Osteopaste could be a new promising biomaterial for bone repair and has a potential in bone tissue engineering.

scholarly journals Collagen Scaffolds Containing Hydroxyapatite-CaO Fiber Fragments for Bone Tissue Engineering

Polymers ◽  
2020 ◽  
Vol 12 (5) ◽  
pp. 1174 ◽  
Author(s):  
Shiao-Wen Tsai ◽  
Sheng-Siang Huang ◽  
Wen-Xin Yu ◽  
Yu-Wei Hsu ◽  
Fu-Yin Hsu
Keyword(s):  
Tissue Engineering ◽  
Bone Tissue Engineering ◽  
Bone Regeneration ◽  
Bone Tissue ◽  
Drug Loading ◽  
Sol Gel ◽  
Regeneration Ability ◽  
Burst Release ◽  
Electrospinning Technique

Collagen (COL) and hydroxyapatite (HAp) are the major components of bone, therefore, COL-HAp composites have been widely used as bone substitutes to promote bone regeneration. We have reported that HAp-CaO fibers (HANFs), which were fabricated by a sol-gel route followed by an electrospinning technique, possessed good drug-loading efficiency and limited the burst release of tetracycline. In the present study, we used HANF fragments to evaluate the effects of COL-HANF scaffolds on MG63 osteoblast-like cell behaviors. COL-HANF composite scaffolds in which the average diameter of HANFs was approximately 461 ± 186 nm were fabricated by a freeze-drying process. The alkaline phosphatase activity and the protein expression levels of OCN and BSP showed that compared with COL alone, the COL-HANF scaffold promoted the differentiation of MG63 osteoblast-like cells. In addition, the bone regeneration ability of the COL-HANF scaffold was examined by using a rabbit condylar defect model in vivo. The COL-HANF scaffold was biodegradable and promoted bone regeneration eight weeks after the operation. Hence, we concluded that the COL-HANF scaffold has potential as a bone graft for bone tissue engineering.

scholarly journals Genetically Engineered-MSC Therapies for Non-unions, Delayed Unions and Critical-size Bone Defects

2019 ◽  
Vol 20 (14) ◽  
pp. 3430 ◽  
Author(s):  
Jaime Freitas ◽  
Susana Gomes Santos ◽  
Raquel Madeira Gonçalves ◽  
José Henrique Teixeira ◽  
Mário Adolfo Barbosa ◽  
...  
Keyword(s):  
Bone Regeneration ◽  
Animal Studies ◽  
Bone Repair ◽  
Critical Size ◽  
Clinical Problem ◽  
Cell Types ◽  
Bone Defects ◽  
Genetically Engineered ◽  
Beneficial Effects

The normal bone regeneration process is a complex and coordinated series of events involving different cell types and molecules. However, this process is impaired in critical-size/large bone defects, with non-unions or delayed unions remaining a major clinical problem. Novel strategies are needed to aid the current therapeutic approaches. Mesenchymal stem/stromal cells (MSCs) are able to promote bone regeneration. Their beneficial effects can be improved by modulating the expression levels of specific genes with the purpose of stimulating MSC proliferation, osteogenic differentiation or their immunomodulatory capacity. In this context, the genetic engineering of MSCs is expected to further enhance their pro-regenerative properties and accelerate bone healing. Herein, we review the most promising molecular candidates (protein-coding and non-coding transcripts) and discuss the different methodologies to engineer and deliver MSCs, mainly focusing on in vivo animal studies. Considering the potential of the MSC secretome for bone repair, this topic has also been addressed. Furthermore, the promising results of clinical studies using MSC for bone regeneration are discussed. Finally, we debate the advantages and limitations of using MSCs, or genetically-engineered MSCs, and their potential as promoters of bone fracture regeneration/repair.

scholarly journals The Effects of Atmospheric Pressure Argon Plasma Treated Bovine Bone Substitute on Bone Regeneration

Coatings ◽  
2019 ◽  
Vol 9 (12) ◽  
pp. 790
Author(s):  
Jong-Ju Ahn ◽  
Ji-Hyun Yoo ◽  
Eun-Bin Bae ◽  
Gyoo-Cheon Kim ◽  
Jae Joon Hwang ◽  
...  
Keyword(s):  
Bone Regeneration ◽  
Atmospheric Pressure ◽  
Bone Substitute ◽  
Argon Plasma ◽  
Atmospheric Pressure Plasma ◽  
Regeneration Ability ◽  
Bovine Bone ◽  
Significant Difference

This study was undertaken to compare new bone formation between non-expired and expired bovine-derived xenogeneic bone substitute (expired, out-of-use period) and to evaluate the efficacy of argon (Ar)-based atmospheric pressure plasma (APP) treatment on expired bone substitute in rat calvarial defect. The groups were divided into (1) Non/Expired group (Using regular xenografts), (2) Expired group (Using expired xenografts), and (3) Ar/Expired group (Using Ar-based APP treated expired xenografts). Surface observation and cell experiments were performed in vitro. Twelve rats were used for in vivo experiment and the bony defects were created on the middle of the cranium. The bone substitute of each group was implanted into the defective site. After 4 weeks, all the rats were sacrificed, and the volumetric, histologic, and histometric analyses were performed. In the results of osteogenic differentiation and mineralization, Non/Expired and Ar/Expired groups were significantly higher than Expired group (p < 0.05). However, there was no significant difference between groups in the animal study (p > 0.05). Within the limitations of this study, the surface treatment of Ar-based APP has a potential effect on the surface modification of bone grafts. However, there was no significant difference in bone regeneration ability between groups in vivo; thus, studies on APP to enhance bone regeneration should be carried out in the future.

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