scholarly journals Exposure to a youthful circulation rejuvenates bone repair through modulation of β-catenin

2015 ◽  
Vol 6 (1) ◽  
Author(s):  
Gurpreet S. Baht ◽  
David Silkstone ◽  
Linda Vi ◽  
Puviindran Nadesan ◽  
Yasha Amani ◽  
...  
Keyword(s):  
Bone Repair ◽  
Repair Process ◽  
Osteoblastic Differentiation ◽  
Fracture Repair ◽  
Ageing Population ◽  
Haematopoietic Cells ◽  
Age Dependent ◽  
Old Mice

Abstract The capacity for tissues to repair and regenerate diminishes with age. We sought to determine the age-dependent contribution of native mesenchymal cells and circulating factors on in vivo bone repair. Here we show that exposure to youthful circulation by heterochronic parabiosis reverses the aged fracture repair phenotype and the diminished osteoblastic differentiation capacity of old animals. This rejuvenation effect is recapitulated by engraftment of young haematopoietic cells into old animals. During rejuvenation, β-catenin signalling, a pathway important in osteoblast differentiation, is modulated in the early repair process and required for rejuvenation of the aged phenotype. Temporal reduction of β-catenin signalling during early fracture repair improves bone healing in old mice. Our data indicate that young haematopoietic cells have the capacity to rejuvenate bone repair and this is mediated at least in part through β-catenin, raising the possibility that agents that modulate β-catenin can improve the pace or quality of fracture repair in the ageing population.

scholarly journals Interactions between MSCs and Immune Cells: Implications for Bone Healing

2015 ◽  
Vol 2015 ◽  
pp. 1-17 ◽  
Author(s):  
Tracy K. Kovach ◽  
Abhijit S. Dighe ◽  
Peter I. Lobo ◽  
Quanjun Cui
Keyword(s):  
Fracture Healing ◽  
Bone Healing ◽  
Immune Cells ◽  
Bone Repair ◽  
Repair Process ◽  
The United States ◽  
Fracture Repair ◽  
Cell Based Therapy

It is estimated that, of the 7.9 million fractures sustained in the United States each year, 5% to 20% result in delayed or impaired healing requiring therapeutic intervention. Following fracture injury, there is an initial inflammatory response that plays a crucial role in bone healing; however, prolonged inflammation is inhibitory for fracture repair. The precise spatial and temporal impact of immune cells and their cytokines on fracture healing remains obscure. Some cytokines are reported to be proosteogenic while others inhibit bone healing. Cell-based therapy utilizing mesenchymal stromal cells (MSCs) is an attractive option for augmenting the fracture repair process. Osteoprogenitor MSCs not only differentiate into bone, but they also exert modulatory effects on immune cells via a variety of mechanisms. In this paper, we review the current literature on bothin vitroandin vivostudies on the role of the immune system in fracture repair, the use of MSCs in the enhancement of fracture healing, and interactions between MSCs and immune cells. Insight into this paradigm can provide valuable clues in identifying cellular and noncellular targets that can potentially be modulated to enhance both natural bone healing and bone repair augmented by the exogenous addition of MSCs.

Systemic Mesenchymal Stem Cell Delivery and Axial Mechanical Stimulation Accelerate Fracture Healing

2008 ◽  
Author(s):  
Aaron S. Weaver ◽  
Yu-Ping Su ◽  
Dana L. Begun ◽  
Ralph T. Zade ◽  
Andrea I. Alford ◽  
...  
Keyword(s):  
Fracture Healing ◽  
Bone Repair ◽  
Local Environment ◽  
Cell Types ◽  
Repair Process ◽  
Fracture Site ◽  
Fracture Repair ◽  
Stem Cell Delivery ◽  
Numerous Cell ◽  
Local Cell

Fracture healing is a complex process involving numerous cell types, whose actions are regulated by many factors in their local environment. Mechanical factors are known to exert a strong influence on the actions of these cells and the progression of the repair process. While prior studies have investigated the effect of physical forces on cell differentiation, biofactor expression, and mechanical competence of repair, the mechanosensory and response mechanisms are poorly understood. This study was designed to explore the influence of a controlled mechanical environment on temporal aspects of the bone repair process. Specifically, this study examines how the timing of an applied strain influences local cell behavior during fracture repair, and how this load affects the migration of systemically introduced mesenchymal stem cells (MSCs) to the fracture site.

Mechanical properties and in-vivo performance of calcium phosphate cement—chitosan fibre composite

2008 ◽  
Vol 222 (3) ◽  
pp. 347-353 ◽  
Author(s):  
Q Lian ◽  
D-C Li ◽  
J-K He ◽  
Z Wang
Keyword(s):  
Mechanical Properties ◽  
Calcium Phosphate ◽  
Calcium Phosphate Cement ◽  
Bone Repair ◽  
Fibre Composite ◽  
Repair Process ◽  
Fibre Volume ◽  
Dimensional Structure ◽  
Fibre Structure

Self-hardened calcium phosphate cement (CPC) sets to form hydroxyapatite and possesses excellent osteoconductivity. However, lack of macroporosity and low strength constrain its application in bone tissue engineering. Recent studies have incorporated various fibres into CPC to improve its mechanical strength. The present approach focused on the reinforcement of CPC with chitosan fibres and then the effects of the fibre structure on the mechanical properties and macrochannels formation characteristics of CPC—fibre composite were investigated. Chitosan fibres of diameter 200 μm were used to fabricate two types of three-dimensional structure, which were then coated with collagen and incorporated into CPC to fabricate CPC—fibre implants with a fibre volume content of 5 per cent. The compressive strength of the CPC—fibre implant was 33 MPa when the strain was 2.4 per cent, which is fourfold higher than that of the CPC control. Nine cylindrical implants including six CPC—fibre implants were implanted in the bone defects of nine dogs and were then post-operatively observed. After 20 weeks in vivo, new callus from the healthy tissue of the defect entirely integrated with the CPC—fibre implant and new bone was formed as the implant degraded. Scanning electronic microscopy images indicated that macrochannels were formed in the CPC—fibre implants with the degradation of fibres, but only micropores with a scale of less than 50 μm could be observed in the CPC control. Briefly, the incorporation of a suitable chitosan-fibre structure into a CPC implant not only could improve its mechanical properties but also facilitated the bone repair process in vivo.

Macrophages Promote Osteoblastic Differentiation In Vivo: Implications in Fracture Repair and Bone Homeostasis

2015 ◽  
Vol 30 (6) ◽  
pp. 1090-1102 ◽  
Author(s):  
Linda Vi ◽  
Gurpreet S Baht ◽  
Heather Whetstone ◽  
Adeline Ng ◽  
Qingxia Wei ◽  
...  
Keyword(s):  
Osteoblastic Differentiation ◽  
Fracture Repair ◽  
Bone Homeostasis

scholarly journals Bioactive Factors-imprinted Scaffold Vehicles for Promoting Bone Healing: The Potential Strategies and the Confronted Challenges for Clinical Production

2020 ◽  
Vol 1 (1) ◽  
pp. 37-54
Author(s):  
Peng-Peng Xue ◽  
Jian-dong Yuan ◽  
Qing Yao ◽  
Ying-Zheng Zhao ◽  
He-Lin Xu
Keyword(s):  
Bone Morphogenetic Proteins ◽  
Bone Healing ◽  
Half Life ◽  
Wound Repair ◽  
Large Scale ◽  
Bone Repair ◽  
Callus Formation ◽  
Fracture Repair ◽  
Enzyme Degradation

Abstract Wound repair of bone is a complicated multistep process orchestrated by inflammation, angiogenesis, callus formation, and bone remodeling. Many bioactive factors (BFs) including cytokine and growth factors (GFs) have previously been reported to be involved in regulating wound healing of bone and some exogenous BFs such as bone morphogenetic proteins (BMPs) were proven to be helpful for improving bone healing. In this regard, the BFs reported for boosting bone repair were initially categorized according to their regulatory mechanisms. Thereafter, the challenges including short half-life, poor stability, and rapid enzyme degradation and deactivation for these exogenous BFs in bone healing are carefully outlined in this review. For these issues, BFs-imprinted scaffold vehicles have recently been reported to promote the stability of BFs and enhance their half-life in vivo. This review is focused on the incorporation of BFs into the modulated biomaterials with various forms of bone tissue engineering applications: firstly, rigid bone graft substitutes (BGSs) were used to imprint BFs for large scale bone defect repair; secondly, the soft sponge-like scaffold carrying BFs is discussed as filling materials for the cavity of bone defects; thirdly, various injectable vehicles including hydrogel, nanoparticles, and microspheres for the delivery of BFs were also introduced for irregular bone fracture repair. Meanwhile, the challenges for BFs-imprinted scaffold vehicles are also analyzed in this review.

scholarly journals Integrin-specific hydrogels modulate transplanted human bone marrow-derived mesenchymal stem cell survival, engraftment, and reparative activities

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Amy Y. Clark ◽  
Karen E. Martin ◽  
José R. García ◽  
Christopher T. Johnson ◽  
Hannah S. Theriault ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Stem Cell ◽  
Cell Survival ◽  
Bone Repair ◽  
Osteoblastic Differentiation ◽  
Human Bone ◽  
Human Bone Marrow ◽  
Cell Therapies

AbstractStem cell therapies are limited by poor cell survival and engraftment. A hurdle to the use of materials for cell delivery is the lack of understanding of material properties that govern transplanted stem cell functionality. Here, we show that synthetic hydrogels presenting integrin-specific peptides enhance the survival, persistence, and osteo-reparative functions of human bone marrow-derived mesenchymal stem cells (hMSCs) transplanted in murine bone defects. Integrin-specific hydrogels regulate hMSC adhesion, paracrine signaling, and osteoblastic differentiation in vitro. Hydrogels presenting GFOGER, a peptide targeting α2β1 integrin, prolong hMSC survival and engraftment in a segmental bone defect and result in improved bone repair compared to other peptides. Integrin-specific hydrogels have diverse pleiotropic effects on hMSC reparative activities, modulating in vitro cytokine secretion and in vivo gene expression for effectors associated with inflammation, vascularization, and bone formation. These results demonstrate that integrin-specific hydrogels improve tissue healing by directing hMSC survival, engraftment, and reparative activities.

scholarly journals In Vivo Biological Behavior of Polymer Scaffolds of Natural Origin in the Bone Repair Process

Molecules ◽  
2021 ◽  
Vol 26 (6) ◽  
pp. 1598
Author(s):  
Fernando Bento Cunha ◽  
Karina Torres Pomini ◽  
Ana Maria de Guzzi Plepis ◽  
Virgínia da Conceição Amaro Martins ◽  
Eduardo Gomes Machado ◽  
...  
Keyword(s):  
Bone Defect ◽  
Bone Repair ◽  
Bone Growth ◽  
Critical Size ◽  
Blood Clot ◽  
Collagen Matrix ◽  
Repair Process ◽  
Biological Behavior ◽  
Control Group

Autologous bone grafts, used mainly in extensive bone loss, are considered the gold standard treatment in regenerative medicine, but still have limitations mainly in relation to the amount of bone available, donor area, morbidity and creation of additional surgical area. This fact encourages tissue engineering in relation to the need to develop new biomaterials, from sources other than the individual himself. Therefore, the present study aimed to investigate the effects of an elastin and collagen matrix on the bone repair process in critical size defects in rat calvaria. The animals (Wistar rats, n = 30) were submitted to a surgical procedure to create the bone defect and were divided into three groups: Control Group (CG, n = 10), defects filled with blood clot; E24/37 Group (E24/37, n = 10), defects filled with bovine elastin matrix hydrolyzed for 24 h at 37 °C and C24/25 Group (C24/25, n = 10), defects filled with porcine collagen matrix hydrolyzed for 24 h at 25 °C. Macroscopic and radiographic analyses demonstrated the absence of inflammatory signs and infection. Microtomographical 2D and 3D images showed centripetal bone growth and restricted margins of the bone defect. Histologically, the images confirmed the pattern of bone deposition at the margins of the remaining bone and without complete closure by bone tissue. In the morphometric analysis, the groups E24/37 and C24/25 (13.68 ± 1.44; 53.20 ± 4.47, respectively) showed statistically significant differences in relation to the CG (5.86 ± 2.87). It was concluded that the matrices used as scaffolds are biocompatible and increase the formation of new bone in a critical size defect, with greater formation in the polymer derived from the intestinal serous layer of porcine origin (C24/25).

An In vivo Experimental Study on Investigation of the Osseointegration of Zeolites A and Silicalite in Rats

2021 ◽  
Author(s):  
Taşkın Ceyhan ◽  
Ahmet Gülçubuk ◽  
Melkon Tatlıer ◽  
Damla Haktanır ◽  
Hümeyra Kocaelli
Keyword(s):  
Bone Repair ◽  
Glass Ceramics ◽  
Repair Process ◽  
Tissue Reaction ◽  
Histological Evaluation ◽  
Polycrystalline Materials ◽  
Time Intervals ◽  
Naturally Occurring ◽  
Medical Materials

Background: Zeolites are naturally occurring and can be artificially synthesized hydrated microporous crystallized aluminosilicates. Thus far, medical materials have comprised polycrystalline materials, glass, glass-ceramics and ceramic-filled composites for bone repair. The study aimed to investigate the potential in vivo osseointegration of two types of zeolites (A and silicalite) in rats by histologically presenting the repair process. Methods: Bone cavities of 1 mm3 were formed in rats and filled either with zeolite A or silicalite to investigate the possibility of using zeolites to repair bone defects. A comparative histological evaluation was performed regarding the interaction of zeolites with bone tissue and their osseointegration capacity for 15, 30 and 45-day intervals. Result: According to the results obtained, the growth of both fibrous and bone tissues took place around the zeolites placed in the live organism. It was observed that the zeolites used in this study did not give rise to necrosis, local tissue reaction, allergic or and any other harmful response. In conclusion, histopathology revealed that zeolites A and silicalite were biocompatible with the bone and could integrate with it at certain time intervals.

Enhancing Bone Regeneration by Synthetic Peptide-Coated CMP Granules

2006 ◽  
Vol 309-311 ◽  
pp. 215-218
Author(s):  
D.H. Yoon ◽  
H.J. Kim ◽  
J.H. Lee ◽  
M.J. Cho ◽  
Hong In Shin
Keyword(s):  
Bone Regeneration ◽  
Synthetic Peptide ◽  
Bone Repair ◽  
Cellular Proliferation ◽  
Surface Modifications ◽  
Osteoblastic Differentiation ◽  
Cellular Attachment ◽  
Recombinant Peptides

For effective bone regeneration, various surface modifications have been tried. In an effort to improve osteogenic repair potential, we evaluated recombinant peptides containing the RGD domain as a bioactive molecule for tissue-engineered bone regeneration. The synthetic peptides slightly suppressed cellular proliferation in the in vitro culture system but induced favorable osteoblastic differentiation, which was determined by MTT and ALP activity staining, respectively. The synthetic peptide coated CMP granules, which were implanted into the mandibular bone defects showed more favorable bone repair compared to the non-coated CMP implantation. In addition, there were not any sign of inflammatory reaction. These findings suggest that synthesized peptides containing the RGD domain enhance cellular attachment and osteogenic activity in vivo condition and that the peptide-coated CMP granules can serve as a biocompatible bone substitute.

scholarly journals Adenoviral Delivery of the VEGF and BMP-6 Genes to Rat Mesenchymal Stem Cells Potentiates Osteogenesis

2013 ◽  
Vol 2013 ◽  
pp. 1-9 ◽  
Author(s):  
Jesse Seamon ◽  
Xiuli Wang ◽  
Fuai Cui ◽  
Tom Keller ◽  
Abhijit S. Dighe ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Bone Repair ◽  
Adenovirus Vector ◽  
Osteoblastic Differentiation ◽  
Dna Encoding ◽  
Bone Injury ◽  
Adenoviral Delivery ◽  
Two Factors

The combined delivery of mesenchymal stem cells (MSCs), vascular endothelial growth factor (VEGF), and bone morphogenetic protein (BMP) to sites of bone injury results in enhanced repair compared to the administration of a single factor or a combination of two factors. Based on these findings, we hypothesized that coexpression of VEGF and BMP-6 genes would enhance the osteoblastic differentiation of rat bone-marrow-derived stem cells (rMSCs) and osteogenesis by comparison to rMSCs that do not express VEGF and BMP-6. We prepared a GFP tagged adenovirus vector (Ad-VEGF+BMP-6) that contained DNA encoding the hVEGF and hBMP-6 genes. rMSCs were transduced with the virus, and the successful transduction was confirmed by green fluorescence and by production of VEGF and BMP-6 proteins. The cells were cultured to assess osteoblastic differentiation or administered in the Fischer 344 rats to assess bone formation. Mineralization of rMSCs transduced with Ad-VEGF+BMP-6 was significantly enhanced over the nontransduced rMSCs. Only transduced rMSCs could induce osteogenesis in vivo, whereas Ad-VEGF+BMP-6 or nontransduced rMSCs alone did not induce osteogenesis. The data suggests that the combined delivery of MSCs, VEGF, and BMP-6 is an attractive option for bone repair therapy.

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