Bone morphogenetic proteins in tissue engineering: the road from the laboratory to the clinic, part I (basic concepts)

Bessa, Paulo C.; Casal, Margarida; Reis, Rui L.

doi:10.1002/term.63

Cited by 275 publications

(251 citation statements)

References 169 publications

(212 reference statements)

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“…Among these, bone morphogenetic proteins (BMPs) are probably the most important GFs involved [6,7,50]. BMPs regulate osteogenesis at two different levels: (1) the commitment of skeletal progenitor cells and (2) the maturation of osteoblasts in postnatal development [54].…”

Section: Introductionmentioning

confidence: 99%

Starch-poly-є-caprolactone Microparticles Reduce the Needed Amount of BMP-2

Balmayor

Feichtinger

Azevedo

et al. 2009

Clin Orthop Relat Res

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BMP-2 is currently administered clinically using collagen matrices often requiring large amounts of BMP-2 due to burst release over a short period of time. We developed and tested a novel injectable drug delivery system consisting of starch-poly-e-caprolactone microparticles for inducing osteogenesis and requiring smaller amounts of BMP-2. We evaluated BMP-2 encapsulation efficiency and the in vitro release profile by enzyme-linked immunosorbent assay. BMP-2 was rapidly released during the first 12 hours, followed by sustained release for up to 10 days. We then evaluated the osteogenic potential of dexamethasone (standard osteogenic induction agent) and BMP-2 after incorporation and during release using an osteo/myoblast cell line (C2C12). Alkaline phosphatase activity was increased by released BMP-2. Mineralization occurred after stimulation with BMP-2-loaded microparticles. A luciferase assay for osteocalcin promoter activity showed high levels of activity upon treatment with BMP-2-loaded microparticles. In contrast, no osteogenesis occurred in C2C12 cells using dexamethasone-loaded microparticles. However, human adipose stem cells exposed to the microparticles produced high amounts of alkaline phosphatase. The data suggest starch-poly-e-caprolactone microparticles are suitable carriers for the incorporation and controlled release of glucocorticoids and growth factors. Specifically, they reduce the amount of BMP-2 needed and allow more sustained osteogenic effects.

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Section: Introductionmentioning

confidence: 99%

Starch-poly-є-caprolactone Microparticles Reduce the Needed Amount of BMP-2

Balmayor

Feichtinger

Azevedo

et al. 2009

Clin Orthop Relat Res

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“…The identification of an entirely unique family of growth factors, bone morphogenetic proteins (BMPs), has led to an increase in the understanding of bone formation and regeneration (15). BMPs regulate cartilage and bone differentiation in the body as initiated by the binding of BMPs to specific cell-surface receptors (bone morphogenic protein receptors).…”

mentioning

confidence: 99%

“…BMPs regulate cartilage and bone differentiation in the body as initiated by the binding of BMPs to specific cell-surface receptors (bone morphogenic protein receptors). This activates a signalling cascade inside the cells that results in the production and recruitment of proteins necessary for transformation into cartilage-and bone matrix-synthesizing cells, i.e., chondroblasts and osteoblasts, respectively (15). Bone formation or ossification continues through a series of events that include formation of cartilage, hypertrophy, and calcification of the deposited cartilage, vascular invasion, differentiation of osteoblasts and mineralization of bone.…”

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confidence: 99%

Active multilayered capsules for in vivo bone formation

Facca

Cortez

Mendoza-Palomares

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

118

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Interest in the development of new sources of transplantable materials for the treatment of injury or disease has led to the convergence of tissue engineering with stem cell technology. Bone and joint disorders are expected to benefit from this new technology because of the low self-regenerating capacity of bone matrix secreting cells. Herein, the differentiation of stem cells to bone cells using active multilayered capsules is presented. The capsules are composed of poly-L-glutamic acid and poly-L-lysine with active growth factors embedded into the multilayered film. The bone induction from these active capsules incubated with embryonic stem cells was demonstrated in vitro. Herein, we report the unique demonstration of a multilayered capsule-based delivery system for inducing bone formation in vivo. This strategy is an alternative approach for in vivo bone formation. Strategies using simple chemistry to control complex biological processes would be particularly powerful, as they make production of therapeutic materials simpler and more easily controlled.

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“…Although recombinant human (rh)BMP2 is the most widely utilized recombinant BMP with Food and Drug Administration (FDA)'s approval (Bessa, Casal, & Reis, 2008a, 2008b; Carreira et al, 2014), many investigators remain surprised to learn that other BMPs have previously been characterized as more osteogenic than the currently approved BMP2 or BMP7 (Kang et al, 2004). In two pioneering study conducted over a decade ago investigating all 14 BMPs, it was found that BMP6 and BMP9 stimulated the highest alkaline phosphatase (ALP) expression in vitro (Cheng et al, 2003) and had greater potential for orthotropic ossification in vivo (Kang et al, 2004).…”

Section: Introductionmentioning

confidence: 99%

Absorbable collagen sponges loaded with recombinant bone morphogenetic protein 9 induces greater osteoblast differentiation when compared to bone morphogenetic protein 2

Fujioka‐Kobayashi

Benoit

Saulačić

et al. 2017

Clinical & Exp Dental Res

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The use of growth factors for the regeneration of soft and hard tissues has been utilized extensively in dental medicine over the past decade. Recently our group found that recombinant human bone morphogenetic protein 9 (rhBMP9) was more osteopromotive than recombinant human bone morphogenetic protein 2 (rhBMP2) when combined with a deprotenized bovine bone mineral bone grafting material. The aim of the present in vitro study was to evaluate the regenerative potential of an absorbable collagen sponge(ACS) specifically designed for extraction socket healing loaded with rhBMP9 when compared to rhBMP2. The adsorption and release kinetics of rhBMP2 and rhBMP9 were first investigated by enzyme‐linked immunosorbent assay quantification. Then, the cellular effects of stromal cell line (ST2) preosteoblasts were investigated utilizing four groups including rhBMP2 and rhBMP9 at both low(10 ng/ml) and high(100 ng/ml) concentrations loaded onto ACS. Cellular attachment(8 hours) and proliferation(1, 3, and 5 days) as well as osteoblast differentiation were investigated by real‐time polymerase chain reaction (PCR) at 3 and 14 days, alkaline phosphatase (ALP) activity at 7 days, and alizarin red staining at 14 days. ACS fully adsorbed both rhBMP2 and rhBMP9 that were slowly released up to 10 days. Although neither rhBMP2 nor rhBMP9 had any effects on cell attachment or proliferation, pronounced effects were observed on osteoblast differentiation. ALP activity was increased seven‐fold with rhBMP2‐high, whereas a marked 10‐fold and 20‐fold increase was observed with rhBMP9‐low and high loaded to ACS, respectively. Furthermore, mRNA levels of collagen1, ALP, bone sialoprotein, and osteocalcin were all significantly higher for rhBMP9 when compared to control or rhBMP2 groups. Alizarin red staining further confirmed that rhBMP9‐low and high demonstrated marked increases in mineralization potential when compared to rhBMP2‐high. The results demonstrate the marked effect of rhBMP9 on osteoblast differentiation when combined with ACS in comparison to rhBMP2 at doses as much as 10 times lower. Further in vivo studies are necessary to investigate whether the regenerative potential is equally as potent.

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Bone morphogenetic proteins in tissue engineering: the road from the laboratory to the clinic, part I (basic concepts)

Cited by 275 publications

References 169 publications

Starch-poly-є-caprolactone Microparticles Reduce the Needed Amount of BMP-2

Starch-poly-є-caprolactone Microparticles Reduce the Needed Amount of BMP-2

Active multilayered capsules for in vivo bone formation

Absorbable collagen sponges loaded with recombinant bone morphogenetic protein 9 induces greater osteoblast differentiation when compared to bone morphogenetic protein 2

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