Evaluation of the ability of collagen–glycosaminoglycan scaffolds with or without mesenchymal stem cells to heal bone defects in Wistar rats

Alhag, Mohamed; Farrell, Eric; Toner, Mary; Lee, Clive; O’Brien, Fergal J.; Claffey, Noel

doi:10.1007/s10006-011-0299-0

Cited by 20 publications

(12 citation statements)

References 45 publications

(45 reference statements)

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“…Scaffolds derived from type I collagen fabricated through a freeze-drying process showed immense potential in bone tissue engineering464748. Calcium phosphate-incorporated collagen scaffolds have been investigated as a means to improve the bioactivity and mechanical properties, mimicking the extracellular matrix of bone4950.…”

Section: Discussionmentioning

confidence: 99%

Enhanced osteogenesis and angiogenesis by mesoporous hydroxyapatite microspheres-derived simvastatin sustained release system for superior bone regeneration

Sun

et al. 2017

Sci Rep

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Biomaterials with both excellent osteogenic and angiogenic activities are desirable to repair massive bone defects. In this study, simvastatin with both osteogenic and angiogenic activities was incorporated into the mesoporous hydroxyapatite microspheres (MHMs) synthesized through a microwave-assisted hydrothermal method using fructose 1,6-bisphosphate trisodium salt (FBP) as an organic phosphorous source. The effects of the simvastatin-loaded MHMs (S-MHMs) on the osteogenic differentiation of rat bone marrow mesenchymal stem cells (rBMSCs) and angiogenesis in EA.hy926 cells were investigated. The results showed that the S-MHMs not only enhanced the expression of osteogenic markers in rBMSCs but also promoted the migration and tube formation of EA.hy926 cells. Furthermore, the S-MHMs were incorporated into collagen matrix to construct a novel S-MHMs/collagen composite scaffold. With the aid of MHMs, the water-insoluble simvastatin was homogenously incorporated into the hydrophilic collagen matrix and presented a sustained release profile. In vivo experiments showed that the S-MHMs/collagen scaffolds enhanced the bone regeneration and neovascularization simultaneously. These results demonstrated that the water-insoluble simvastatin could be incorporated into the MHMs and maintained its biological activities, more importantly, the S-MHMs/collagen scaffolds fabricated in this study are of immense potential in bone defect repair by enhancing osteogenesis and angiogenesis simultaneously.

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Section: Discussionmentioning

confidence: 99%

Enhanced osteogenesis and angiogenesis by mesoporous hydroxyapatite microspheres-derived simvastatin sustained release system for superior bone regeneration

Sun

et al. 2017

Sci Rep

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“…A critical‐sized rodent calvarial defect model was used in this study. This model is utilised in almost half of all critical defect studies for bone regeneration (O'Loughlin et al, ) and is well established within our laboratory (Alhag et al, ; Lyons et al, ). There were two study groups used: (a) a GF‐free scaffold group ( n = 8) and (b) a dual GF‐loaded scaffold group ( n = 8), total animals = 16.…”

Section: Methodsmentioning

confidence: 99%

Rapid healing of a critical‐sized bone defect using a collagen‐hydroxyapatite scaffold to facilitate low dose, combinatorial growth factor delivery

Walsh

Raftery

Chen

et al. 2019

J Tissue Eng Regen Med

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The healing of large, critically sized bone defects remains an unmet clinical need in modern orthopaedic medicine. The tissue engineering field is increasingly using biomaterial scaffolds as 3D templates to guide the regenerative process, which can be further augmented via the incorporation of recombinant growth factors. Typically, this necessitates supraphysiological doses of growth factor to facilitate an adequate therapeutic response. Herein, we describe a cell‐free, biomaterial implant which is functionalised with a low dose, combinatorial growth factor therapy that is capable of rapidly regenerating vascularised bone tissue within a critical‐sized rodent calvarial defect. Specifically, we demonstrate that the dual delivery of the growth factors bone morphogenetic protein‐2 (osteogenic) and vascular endothelial growth factor (angiogenic) at a low dose (5 μg/scaffold) on an osteoconductive collagen‐hydroxyapatite scaffold is highly effective in healing these critical‐sized bone defects. The high affinity between the hydroxyapatite component of this biomimetic scaffold and the growth factors functions to sequester them locally at the defect site. Using this growth factor‐loaded scaffold, we show complete bridging of a critical‐sized calvarial defect in all specimens at a very early time point of 4 weeks, with a 28‐fold increase in new bone volume and seven‐fold increase in new bone area compared with a growth factor‐free scaffold. Overall, this study demonstrates that a collagen‐hydroxyapatite scaffold can be used to locally harness the synergistic relationship between osteogenic and angiogenic growth factors to rapidly regenerate bone tissue without the need for more complex controlled delivery vehicles or high total growth factor doses.

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“…In our laboratory, we have developed a series of scaffolds from type I collagen and the abundant polysaccharide, glycosaminoglycan, to produce highly porous collagen-glycosaminoglycan (CG) scaffolds by using a controlled freezedrying process [4][5][6]. These scaffolds have an optimised composition to facilitate osteogenesis [7] and have been shown to enhance bone repair in vivo in minimally loaded calvarial defects [8][9][10].…”

Section: Introductionmentioning

confidence: 99%

Hypoxia-mimicking bioactive glass/collagen glycosaminoglycan composite scaffolds to enhance angiogenesis and bone repair

et al. 2015

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Evaluation of the ability of collagen–glycosaminoglycan scaffolds with or without mesenchymal stem cells to heal bone defects in Wistar rats

Cited by 20 publications

References 45 publications

Enhanced osteogenesis and angiogenesis by mesoporous hydroxyapatite microspheres-derived simvastatin sustained release system for superior bone regeneration

Enhanced osteogenesis and angiogenesis by mesoporous hydroxyapatite microspheres-derived simvastatin sustained release system for superior bone regeneration

Rapid healing of a critical‐sized bone defect using a collagen‐hydroxyapatite scaffold to facilitate low dose, combinatorial growth factor delivery

Hypoxia-mimicking bioactive glass/collagen glycosaminoglycan composite scaffolds to enhance angiogenesis and bone repair

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