Enhancement of the biological activity of BMP‐2 by synthetic dextran derivatives

Dubreucq, Guy; Meunier, Alain; Dahri-Correia, Latifa; Sedel, L.; Petite, Hervé; Logeart-Avramoglou, Delphine

doi:10.1002/jbm.a.31884

Cited by 27 publications

(30 citation statements)

References 45 publications

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“…A typical coated 3DP scaffold used for in vitro and in vivo tests weighed 14 mg and released 10.6 +/− 0.3 ug of total BMP-2 from the scaffold surface. The quantities released are on par with successful in vivo bulk release approaches, such as the collagen sponge, but the volumetric loading density of our LbL film (10 μg BMP-2/mm 3) , is three orders of magnitude higher than typical bulk releasing films[24, 25]. It is interesting to note that BMP-2 release can be controlled and sustained, even from such an ultrathin LbL coating.…”

Section: Resultsmentioning

confidence: 81%

“…These LbL films therefore have the unique advantage of an effective reservoir large enough to allow significant drug encapsulation. However, this LbL coating remains orders of magnitude thinner than traditional bulk degradation polymer delivery models [24, 25] (that are typically millimeter to sub-millimeter in scale) and is conformal to the coated surface, allowing applicability to a wide variety of existing implant technologies.…”

Section: Resultsmentioning

confidence: 99%

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Tissue integration of growth factor-eluting layer-by-layer polyelectrolyte multilayer coated implants

et al. 2011

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Drug eluting coatings that can direct the host tissue response to implanted medical devices have the potential to ameliorate both the medical and financial burden of complications from implantation. However, because many drugs useful in this arena are biologic in nature, a paucity of delivery strategies for biologics, including growth factors, currently limits the control that can be exerted on the implantation environment. Layer-by-Layer (LbL) polyelectrolyte multilayer films are highly attractive as ultrathin biologic reservoirs, due to conformal coating of difficult geometries, aqueous processing likely to preserve fragile protein function, and tenability of incorporation and release profiles. Herein, we describe the first LbL films capable of microgram-scale release of the biologic Bone Morphogenetic Protein 2 (BMP-2), which is capable of directing the host tissue response to create bone from native progenitor cells. Ten micrograms of BMP-2 are released over a period of two weeks in vitro; less than 1% is released in the first 3 hours (compared with commercial collagen matrices which can release up to 60% of BMP-2, too quickly to induce differentiation). BMP-2 released from LbL films retains its ability to induce bone differentiation in MC3T3 E1S4 preosteoblasts, as measured by induction of alkaline phosphatase and stains for calcium (via Alizarin Red) and calcium matrix (via Von Kossa). In vivo, BMP-2 film coated scaffolds were compared with film coated scaffolds lacking BMP-2. BMP-2 coatings implanted intramuscularly were able to initiate host progenitor cells to differentiate into bone, which matured and expanded from four to nine weeks as measured by MicroCT and histology. Such LbL films represent new steps towards controlling and tuning host response to implanted medical devices, which may ultimately increase the success of implanted devices, provide alternative new approaches toward bone wound healing, and lay the foundation for development of a multi-therapeutic release coating.

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Section: Resultsmentioning

confidence: 81%

Section: Resultsmentioning

confidence: 99%

Tissue integration of growth factor-eluting layer-by-layer polyelectrolyte multilayer coated implants

et al. 2011

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“…showed a sustained bioactivity in the cell culture over 6 days. 33 Taken together, adding BMP-2 to the ODM seems to ensure a sufficient cytokine exposure to the hMSC, even if media changes are only carried out every 96 hours.…”

Section: Discussionmentioning

confidence: 99%

Aged human mesenchymal stem cells: the duration of bone morphogenetic protein-2 stimulation determines induction or inhibition of osteogenic differentiation

2014

Orthop Rev

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Bone morphogenetic protein 2 (BMP-2) is a potent osteoinductive cytokine and a growing number of in vitro studies analyze its effects on human mesenchymal stem cells (hMSC) derived from aged or osteoporotic donors. In these studies the exact quantification of osteogenic differentiation capacity is of fundamental interest. Nevertheless, the experimental conditions for osteogenic differentiation of aged hMSC have not been evaluated systematically and vary to a considerable extend. Aim of the study was to assess the influence of cell density, osteogenic differentiation media (ODM) change intervals and duration of BMP-2 stimulation on osteoinduction. Furthermore, time series were carried out for osteogenic differentiation and BMP-2 concentration in ODM/BMP-2 cell culture supernatants. The experiments were performed using hMSC isolated from femoral heads of aged patients undergoing hip joint replacement. ODM change intervals of 96 hours resulted in significantly higher calcium deposition compared to shorter intervals. A cell density of 80% prior to stimulation led to stronger osteoinduction compared to higher cell densities. In ODM, aged hMSC showed a significant induction of calcium deposition after 9 days. Added to ODM, BMP-2 showed a stable concentration in the cell culture supernatants for at least 96 hours. Addition of BMP-2 to ODM for the initial 4 days led to a significantly higher induction of osteogenic differentiation compared to ODM alone. On the other hand, addition of BMP-2 for 21 days almost abrogated the osteoinductive effect of ODM. We could demonstrate that the factors investigated have a substantial impact on the extent of osteogenic differentiation of aged hMSC. Consequently, it is of upmost importance to standardize the experimental conditions in order to enable comparability between different studies. We here define standard conditions for osteogenic differentiation in regard to the specific features of aged hMSC. The finding that BMP-2 induces or inhibits osteogenic differentiation in a time dependent manner indicates an age related alteration in signal transduction of hMSC and requires further investigation.

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“…Modified GAGs can be either sugars that are naturally not sulfated, such as chitosan, dextran, and hyaluronan, 165,166 or oversulfated forms of CS, DS, or HS. The ECM proteins themselves constructed in this manner consist of functional domains that occur in different proteins with varying combinations.…”

Section: Discussionmentioning

confidence: 99%

Artificial Extracellular Matrices to Functionalize Biomaterial Surfaces

Bierbaum

Scharnweber

2011

Comprehensive Biomaterials

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Enhancement of the biological activity of BMP‐2 by synthetic dextran derivatives

Cited by 27 publications

References 45 publications

Tissue integration of growth factor-eluting layer-by-layer polyelectrolyte multilayer coated implants

Tissue integration of growth factor-eluting layer-by-layer polyelectrolyte multilayer coated implants

Aged human mesenchymal stem cells: the duration of bone morphogenetic protein-2 stimulation determines induction or inhibition of osteogenic differentiation

Artificial Extracellular Matrices to Functionalize Biomaterial Surfaces

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