The influence of collagen and hyaluronan matrices on the delivery and bioactivity of bone morphogenetic protein-2 and ectopic bone formation

Bhakta, Gajadhar; Lim, Zophia X.H.; Rai, Bina; Lin, Ting-Xuan; Hui, James; Prestwich, Glenn D.; Wijnen, André J. van; Nurcombe, Victor; Cool, Simon M.

doi:10.1016/j.actbio.2013.07.008

Cited by 94 publications

(77 citation statements)

References 42 publications

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“…S1P did not accelerate the proliferative potential of MSCs, when compared to the control culture. In fact, the proliferation rate of MSCs decreased after S1P supplementation to the culture environment, which is consistent with the results of the study by Schneider et al [57]. The proliferation activity of MSCs was Brought to you by | New York University Bobst Library Technical Services Authenticated Download Date | 6/30/15 7:48 AM particularly reduced after 48 h of stimulation with S1P, even though after 168 h of culture, the proliferative activity of BMSCs and ASCs in cultures with S1P was comparable to the level for the control.…”

Section: Discussionsupporting

confidence: 93%

The effect of the bioactive sphingolipids S1P and C1P on multipotent stromal cells – new opportunities in regenerative medicine

Marycz

Śmieszek

Jeleń

et al. 2015

Cellular and Molecular Biology Letters

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Sphingosine-1-phosphate (S1P) and ceramide-1-phosphate (C1P) belong to a family of bioactive sphingolipids that act as important extracellular signaling molecules and chemoattractants. This study investigated the influence of S1P and C1P on the morphology, proliferation activity and osteogenic properties of rat multipotent stromal cells derived from bone marrow (BMSCs) and subcutaneous adipose tissue (ASCs). We show that S1P and C1P can influence mesenchymal stem cells (MSCs), each in a different manner. S1P stimulation promoted the formation of cellular aggregates of BMSCs and ASCs, while C1P had an effect on the regular growth pattern and expanded intercellular connections, thereby increasing the proliferative activity. Although osteogenic differentiation of MSCs was enhanced by the addition of S1P, the effectiveness of osteoblast differentiation was more evident in BMSCs, particularly when biochemical and molecular marker levels were considered. The results of the functional osteogenic differentiation assay, which includes an evaluation of the efficiency of extracellular matrix mineralization (SEM-EDX), revealed the formation of numerous mineral aggregates in BMSC cultures stimulated with S1P. Our data demonstrated that in an appropriate combination, the bioactive sphingolipids S1P and C1P may find wide application in regenerative medicine, particularly in bone regeneration with the use of MSCs.

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Section: Discussionsupporting

confidence: 93%

The effect of the bioactive sphingolipids S1P and C1P on multipotent stromal cells – new opportunities in regenerative medicine

Marycz

Śmieszek

Jeleń

et al. 2015

Cellular and Molecular Biology Letters

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“…The process can be facilitated by functionalising the surfaces of titanium prostheses with a calcium-phosphate (bone-matrix-like) layer into which the osteoinductive agent BMP-2 has been incorporated (Boyne and Jones, 2004;. By virtue of this mode of delivery, BMP-2 is released gradually and steadily at a low-dose rate during the coating's osteoclast-mediated degradation -not spontaneously and rapidly in a single high-dose burst (Bhakta et al, 2013) -whereby the sustained local formation of bone is promoted (Liu et al, 2005a;Liu et al, 2007). However, BMP-2 is known to induce not only the formation, but also the resorption of bone, and at high concentrations, the equilibrium between the two processes is tipped very much in favour of the latter (Nakamura et al, 2009; Table 6.…”

Section: Discussionmentioning

confidence: 99%

“…BMP-2 is currently applied topically in a free form together with a collagenous matrix (Burkus et al, 2003). The recommended dosage is exceedingly high [e.g.…”

Section: Introductionmentioning

confidence: 99%

Optimisation of BMP-2 dosage for the osseointegration of porous titanium implants in an ovine model

Hunziker

Jovanovic²,

Hörner³

et al. 2016

eCM

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In clinical orthopaedics, total joint replacements and spinal fusions are routine undertakings. Many of the implicated patients suffer from osteoporosis, severe arthrosis or osteopaenia. In individuals thus afflicted, the bony bed lacks the mechanical stability that is a requisite for a firm anchorage of the implant and its functional competence. To promote the bony bondage of an implant it is necessary to induce neo-ossification by the introduction of an osteogenic agent, such as bone morphogenetic protein 2 (BMP-2). Since this growth factor is generally applied in a free form and at high dosages to maximise its osteogenicity, untoward side effects frequently ensue.We hypothesise that the administration of BMP-2 using a suitable delivery vehicle, and its gradual, low dose release therefrom in a cell-mediated manner, would avert the triggering of undesired side effects and enhance its efficacy.To test this postulate, implants of porous titanium were coated with a layer of calcium phosphate into which BMP-2 was biomimetically incorporated at dosages ranging from 0.8 to 500 µg/g of coating material (delivery system) prior to their surgical placement in the tibiae of adult sheep. The volume and the surface area of newly-formed bone were evaluated histomorphometrically after 3 and 6 weeks. The highest values were achieved using BMP-2 dosages of 20 to 100 µg/g of coating: The deposition of bone was confined to the immediate vicinity of the implant and was observed deep within the interstices of its meshwork, to the walls of which it bonded well. The findings of the study attest to the validity of our hypothesis.

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“…The release profiles of drugs depend on the nanocomposite properties, such as the degradation rate, binding affinity, and encapsulation efficiency. Bhakata et al[134] investigated the influence of two different hydrogels from collagen and hyaluronan (thiol-modified hyaluronan, Glycosil™), on the controlled release of BMP-2 for bone formation. The Glycosil hydrogel showed a burst BMP-2 release, followed by a sustained release, whereas the collagen hydrogel showed a burst release when applied to a rat ectopic bone model at three different doses (0.2, 1, or 5 μg).…”

mentioning

confidence: 99%

Dual-controlled release system of drugs for bone regeneration

Kim

Tabata

2015

Advanced Drug Delivery Reviews

113

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The influence of collagen and hyaluronan matrices on the delivery and bioactivity of bone morphogenetic protein-2 and ectopic bone formation

Cited by 94 publications

References 42 publications

The effect of the bioactive sphingolipids S1P and C1P on multipotent stromal cells – new opportunities in regenerative medicine

The effect of the bioactive sphingolipids S1P and C1P on multipotent stromal cells – new opportunities in regenerative medicine

Optimisation of BMP-2 dosage for the osseointegration of porous titanium implants in an ovine model

Dual-controlled release system of drugs for bone regeneration

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