1,721,050 research outputs found
Growth factors for skeletal reconstruction and fracture repair
No full textThe demographic challenges of an ageing population have emphasized the need for processes to augment and repair skeletal tissue loss as a consequence of trauma and/or degeneration. A number of bone growth factors have been shown to be expressed during the course of fracture healing, suggesting a potential role in bone and cartilage formation, and in fracture repair. This review focuses on a select number of these growth factors currently under preclinical and clinical evaluation for skeletal regeneration and fracture repair. The limitations in the use of these skeletal factors to augment bone growth, thus improving quality-of-life and reducing the significant social and economic costs associated with skeletal trauma/loss are also considered
Osteogenesis and angiogenesis: the potential for engineering bone
Full text linkThe repair of large bone defects remains a major clinical orthopaedic challenge. Bone is a highly vascularised tissue reliant on the close spatial and temporal connection between blood vessels and bone cells to maintain skeletal integrity. Angiogenesis thus plays a pivotal role in skeletal development and bone fracture repair. Current procedures to repair bone defects and to provide structural and mechanical support include the use of grafts (autologous, allogeneic) or implants (polymeric or metallic). These approaches face significant limitations due to insufficient supply, potential disease transmission, rejection, cost and the inability to integrate with the surrounding host tissue. The engineering of bone tissue offers new therapeutic strategies to aid musculoskeletal healing. Various scaffold constructs have been employed in the development of tissue-engineered bone; however, an active blood vessel network is an essential pre-requisite for these to survive and integrate with existing host tissue. Combination therapies of stem cells and polymeric growth factor release scaffolds tailored to promote angiogenesis and osteogenesis are under evaluation and development actively to stimulate bone regeneration. An understanding of the cellular and molecular interactions of blood vessels and bone cells will enhance and aid the successful development of future vascularised bone scaffold constructs, enabling survival and integration of bioengineered bone with the host tissue. The role of angiogenic and osteogenic factors in the adaptive response and interaction of osteoblasts and endothelial cells during the multi step process of bone development and repair will be highlighted in this review, with consideration of how some of these key mechanisms can be combined with new developments in tissue engineering to enable repair and growth of skeletal fractures. Elucidation of the processes of angiogenesis, osteogenesis and tissue engineering strategies offer exciting future therapeutic opportunities for skeletal repair and regeneration in orthopaedics
In vitro and in vivo methods to determine the interactions of osteogenic cells with biomaterials
No full textTo assess new biomaterials for possible use as bone graft substitutes, a number of techniques allow interactions with osteoblastic cells to be studied, with respect to effects on proliferation and differentiation of osteoprogenitors. In vitro models include the use of bone explant cultures, fetal rat calvarial-derived osteoblast cells, primary stromal populations, transformed and non-transformed cell lines and immortalized osteoblast cell lines. However, these assessments are limited by the extent of osteogenic differentiation and bone formation that can be observed in vitro, species differences and phenotypic drift of cells cultured in vitro. The use of in vivo experimental systems such as the segmental/calvarial bone defect model, the subcutaneous implant model and the diffusion chamber implantation model circumvent some of these issues and, in the appropriate model, provide data on efficacy, biocompatibility and osteointegration of a biomaterial. The combination of in vitro and in vivo approaches together with the development of new cell labeling techniques, in particular the ability to genetically mark and select specific human bone cell populations provides new avenues for their potential evaluation in combination with appropriate biomaterials for clinical use. These in vitro and in vivo techniques are reviewed and those recently developed for assessment of human osteogenic cells should be applicable to many other cell systems where knowledge of specific human tissue or cell interactions with biomaterials is required
Delivery systems for bone growth factors - the new players in skeletal regeneration
No full textGiven the challenge of an increasing elderly population, the ability to repair and regenerate traumatised or lost tissue is a major clinical and socio-economic need. Pivotal in this process will be the ability to deliver appropriate growth factors in the repair cascade in a temporal and tightly regulated sequence using appropriately designed matrices and release technologies within a tissue engineering strategy. This review outlines the current concepts and challenges in growth factor delivery for skeletal regeneration and the potential of novel delivery matrices and biotechnologies to influence the healthcare of an increasing ageing population
Maternal high-fat diet and offspring expression levels of vitamin K-dependent proteins
No full textStudies suggest that bone growth and development and susceptibility to vascular disease in later life are influenced by maternal nutrition during intrauterine and early postnatal life. There is evidence for a role of vitamin K-dependent proteins (VKDPs) including osteocalcin, matrix Gla protein, periostin, and growth-arrest specific- protein 6, in both bone and vascular development. We have examined whether there are alterations in these VKDPs in bone and vascular tissue from offspring of mothers subjected to a nutritional challenge: a high-fat diet during pregnancy and postnatally, using 6-week-old mouse offspring. Bone site-specific and sex-specific differences across femoral and vertebral bone in male and female offspring were observed. Overall a high-fat maternal diet and offspring diet exacerbated the bone changes observed. Sex-specific differences and tissue-specific differences were observed in VKDP levels in aorta tissue from high-fat diet-fed female offspring from high-fat diet-fed mothers displaying increased levels of Gas6 and Ggcx compared with those of female controls. In contrast, differences were seen in VKDP levels in femoral bone of female offspring with lower expression levels of Mgp in offspring of mothers fed a high-fat diet compared with those of controls. We observed a significant correlation in Mgp expression levels within the femur to measures of bone structure of the femur and vertebra, particularly in the male offspring cohort. In summary, the current study has highlighted the importance of maternal nutrition on offspring bone development and the correlation of VKDPs to bone structure
Assessing the potential of colony morphology for dissecting the CFU-F population from human bone marrow stromal cells
No full textMesenchymal stem cells (MSCs) provide an ideal cell source for bone tissue engineering strategies. However, bone marrow stromal cell (BMSC) populations that contain MSCs are highly heterogeneous expressing a wide variety of proliferative and differentiation potentials. Current MSC isolation methods employing magnetic-activated and fluorescent-activated cell sorting can be expensive and time consuming and, in the absence of specific MSC markers, fail to generate homogeneous populations. We have investigated the potential of various colony morphology descriptors to provide correlations with cell growth potential. Density-independent colony forming unit-fibroblastic (CFU-F) capacity is a MSC prerequisite and resultant colonies display an array of shapes and sizes that might be representative of cell function. Parent colonies were initially categorised according to their diameter and cell density and grouped before passage for the subsequent assessment of progeny colonies. Whereas significant morphological differences between distinct parent populations indicated a correlation with immunophenotype, enhanced CFU-F capacity was not observed when individual colonies were isolated according to these morphological parameters. Colony circularity, an alternative morphological measure, displayed a strong correlation with subsequent cell growth potential. The current study indicates the potential of morphological descriptors for predicting cell growth rate and suggests new directions for research into dissection of human BMSC CFU-F populations
Augmentation of biological and mechanical properties of allograft in impaction bone grafting
No full textBCL-2-associated athanogene-1: A transcriptional regulator mediating chondrocyte survival and differentiation during endochondral ossification
No full textVibration-assisted bone-graft compaction in impaction bone grafting of the femur
No full textThe complications of impaction bone grafting in revision hip replacement includes fracture of the femur and subsidence of the prosthesis. In this in vitro study we aimed to investigate whether the use of vibration, combined with a perforated tamp during the compaction of morsellised allograft would reduce peak loads and hoop strains in the femur as a surrogate marker of the risk of fracture and whether it would also improve graft compaction and prosthetic stability. We found that the peak loads and hoop strains transmitted to the femoral cortex during graft compaction and subsidence of the stem in subsequent mechanical testing were reduced. This innovative technique has the potential to reduce the risk of intra-operative fracture and to improve graft compaction and therefore prosthetic stability
Improving both the biological and mechanical properties of allograft in impaction bone grafting: a role for human bone marrow stromal cells
No full textBackground: The use of fresh morsellised allograft in impaction bone grafting for revision hip surgery remains the gold standard. Bone marrow contains osteogenic progenitor cells that arise from multipotent mesenchymal stem cells and we propose that in combination with allograft will produce a living composite with biological and mechanical potential. This study aimed to determine if human bone marrow stromal cells (HBMSC) seeded onto highly washed morsellised allograft could survive the impaction process, differentiate and proliferate along the osteogenic lineage and confer biomechanical advantage in comparison to impacted allograft aloneMethods: HBMSC were isolated and culture expanded in vitro under osteogenic conditions. Cells were seeded onto prepared morsellised allograft and impacted with a force equivalent to a standard femoral impaction (474J/m2). Samples were incubated for either two or four week periods under osteogenic conditions and analysed for cell viability, histology, immunohistochemistry, and biochemical analysis of cell number and osteogenic enzyme activity. Mechanical shear testing, using a Cam shear tester was performed, under three physiological compressive stresses (50N, 150N, 250N) from which the shear strength, internal friction angle and particle interlocking values were derived.Results: Cell viability of HBMSC post impaction, was confirmed with cell tracker green staining, a marker of viable cells, and observed throughout all samples. There was a significant increase in DNA content and specific alkaline phosphatase activity compared to impacted seeded allograft samples. Immunohistochemical staining for type I collagen confirmed cell differentiation along the osteogenic lineage. Mechanical shear testing demonstrated a statistical significant increase in shear strength and interparticulate cohesion in the allograft / hBMSC group over allograft alone at 2 and 4 week intervals (p<0.001).Conclusion: HBMSC seeded onto allograft resulted in the formation of a living composite capable of withstanding the forces equivalent to a standard femoral impaction. HBMSC under osteogenic conditions were observed to differentiate and proliferate along the osteogenic lineage. In addition, an allograft /HBMSC living composite confers a biomechanical advantage over allograft alone These changes resulting in enhancement of biological and mechanical properties of
bone graft within impaction bone grafting have implications for translation and future change in orthopaedic practice in an increasing ageing population
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