Periodontal repair in dogs: effect of recombinant human bone morphogenetic protein‐12 (rhBMP‐12) on regeneration of alveolar bone and periodontal attachment

Wikesjö, Ulf M.E.; Sorensen, Rachel G.; Kinoshita, Atsuhiro; Li, X. Jian; Wozney, John M.

doi:10.1111/j.1600-051x.2004.00541.x

Cited by 118 publications

(98 citation statements)

References 44 publications

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“…A recent preliminary study in dogs compared rhBMP-12 with rhBMP-2 for the treatment of periodontal defects [129]. The results showed less bone and more functionally oriented PDL between the new bone and new cementum after BMP-12 treatment, contrasting with a more parallel fibre arrangement than BMP-2-treated defects.…”

Section: Growth Factor Applications For Oral and Periodontal Tissue Ementioning

confidence: 99%

Growth factor delivery for oral and periodontal tissue engineering

Kaigler

Cirelli

Giannobile

2006

Expert Opinion on Drug Delivery

169

153

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The treatment of oral and periodontal diseases and associated anomalies accounts for a significant proportion of the healthcare burden, with the manifestations of these conditions being functionally and psychologically debilitating. Growth factors are critical to the development, maturation, maintenance and repair of craniofacial tissues, as they establish an extracellular environment that is conducive to cell and tissue growth. Tissue-engineering principles aim to exploit these properties in the development of biomimetic materials that can provide an appropriate microenvironment for tissue development. These materials have been constructed into devices that can be used as vehicles for delivery of cells, growth factors and DNA. In this review, different mechanisms of drug delivery are addressed in the context of novel approaches to reconstruct and engineer oral-and tooth-supporting structures, namely the periodontium and alveolar bone.

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Section: Growth Factor Applications For Oral and Periodontal Tissue Ementioning

confidence: 99%

Growth factor delivery for oral and periodontal tissue engineering

Kaigler

Cirelli

Giannobile

2006

Expert Opinion on Drug Delivery

169

153

View full text Add to dashboard Cite

show abstract

“…These factors have historically been delivered in solution form, but this has significant limitations due to the short half-lives of these molecules in the body. In contrast, biomaterials-based delivery of these potent signaling molecules can lead to robust responses (Lee et al, 2000;Wikesjö et al, 2004;Chiu et al, 2013). For example, recombinant bone morphogenetic proteins in a collagen carrier are used clinically to promote healing of vertical alveolar bone defects and criticalsized bone defects, and in spinal fusions (McKay et al, 2007).…”

mentioning

confidence: 99%

Multi-lineage MSC Differentiation via Engineered Morphogen Fields

Arany

Huang²,

Gadish³

et al. 2014

J Dent Res

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Tissue loss due to oral diseases requires the healing and regeneration of tissues of multiple lineages. While stem cells are native to oral tissues, a current major limitation to regeneration is the ability to direct their lineage-specific differentiation. This work utilizes polymeric scaffold systems with spatiotemporally controlled morphogen cues to develop precise morphogen fields to direct mesenchymal stem cell differentiation. First, a simple three-layer scaffold design was developed that presented two spatially segregated, lineage-specific cues (Dentinogenic TGF-β1 and Osteogenic BMP4). However, this system resulted in diffuse morphogen fields, as assessed by the in vitro imaging of cell-signaling pathways triggered by the morphogens. Mathematical modeling was then exploited, in combination with incorporation of specific inhibitors (neutralizing antibodies or a small molecule kinase inhibitor) into each morphogen in an opposing spatial pattern as the respective morphogen, to design a five-layer scaffold that was predicted to yield distinct, spatially segregated zones of morphogen signaling. To validate this system, undifferentiated MSCs were uniformly seeded in these scaffold systems, and distinct mineralized tissue differentiation were noted within these morphogen zones. Finally, to demonstrate temporal control over morphogen signaling, latent TGF-β1 was incorporated into one region of a concentric scaffold design, and laser treatment was used to activate the morphogen on-demand and to induce dentin differentiation solely within that specific spatial zone. This study demonstrates a significant advance in scaffold design to generate precise morphogen fields that can be used to develop in situ models to explore tissue differentiation and may ultimately be useful in engineering multi-lineage tissues in clinical dentistry.

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“…23 Wang and colleagues also found evidence of a role for BMP-12 in differentiation by demonstrating that rhesus bone marrow mesenchymal stem cells could be induced to differentiate into tenocytes via BMP-12 gene transfection. 24 In a canine study, Wikesjo et al 25 demonstrated that rhBMP-12 in an absorbable collagen sponge was able to form a functionally oriented periodontal ligament bridging the gap between newly formed bone and cementum. Together, these data strongly support a role for BMP-12/GDF-7 in tenocyte differentiation and matrix remodeling.…”

Section: Discussionmentioning

confidence: 99%

Effect of GDF‐7 deficiency on tail tendon phenotype in mice

Mikic¹,

Entwistle²,

Rossmeier³

et al. 2008

Journal Orthopaedic Research

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The subfamily of growth/differentiation factors (GDFs) known as GDFs 5,6, and 7 appears to be involved in tendon maintenance and repair, although the precise nature of this role has yet to be elucidated. The aim of the present study was to examine the role of GDF-7 in tendon maintenance by studying tail tendon fascicle gene expression, composition, and material property strain rate dependency in 16-week-old male and female GDF-7 deficient mice. GDF-7 deficiency did not affect the biochemical composition of tail tendon fascicles, nor did it significantly affect the tensile material properties obtained at either slow (5%/s) or fast (50%/s) strain rates. Further, no difference was found between genotypes in the strain rate sensitivity of any tensile material property. Consistent with the compositional analyses, QRT-PCR data did not reveal any differences of twofold or greater in the gene expression levels of collagens I, III, V, nor in the proteoglycans decorin, fibromodulin, lumican, biglycan, versican, or aggrecan. Gdf5 expression was upregulated twofold in GDF-7 deficient tail tendons, and Bmp7 expression was downregulated twofold. No notable differences in expression levels for Bmp1-6 or Gdf6 were detected. GDF-5 protein levels were 50% higher in GDF-7 deficient tail tendon compared to wild type tail tendon. The results of this study support the intriguing possibility that compensation by Gdf-5 may be at least in part responsible for the absence of a strong phenotype in GDF-7 deficient mice. ß

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Periodontal repair in dogs: effect of recombinant human bone morphogenetic protein‐12 (rhBMP‐12) on regeneration of alveolar bone and periodontal attachment

Abstract: The outcomes of this study suggest that rhBMP-12 may have significant effects on regeneration of the PDL. Additional preclinical evaluation is needed to confirm these initial observations prior to clinical application.

Cited by 118 publications

References 44 publications

Growth factor delivery for oral and periodontal tissue engineering

Growth factor delivery for oral and periodontal tissue engineering

Multi-lineage MSC Differentiation via Engineered Morphogen Fields

Effect of GDF‐7 deficiency on tail tendon phenotype in mice

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