Copper-doped mesoporous silica nanospheres, a promising immunomodulatory agent for inducing osteogenesis

The application of mesoporous silica nanospheres (MSNs) loaded with drugs/growth factors to induce osteogenic differentiation of stem cells has been trialed by a number of researchers recently. However, limitations such as high cost, complex fabrication and unintended side effects from supraphysiological concentrations of the drugs/growth factors represent major obstacles to any potential clinical application in the near term. In this study we reported an in situ one-pot synthesis strategy of MSNs doped with hypoxia-inducing copper ions and systematically evaluated the nanospheres by in vitro biological assessments. The Cu-containing mesoporous silica nanospheres (Cu-MSNs) had uniform spherical morphology (∼100 nm), ordered mesoporous channels (∼2 nm) and homogeneous Cu distribution. Cu-MSNs demonstrated sustained release of both silicon (Si) and Cu ions and controlled degradability. The Cu-MSNs were phagocytized by immune cells and appeared to modulate a favorable immune environment by initiating proper pro-inflammatory cytokines, inducing osteogenic/angiogenic factors and suppressing osteoclastogenic factors by the immune cells. The immune microenvironment induced by the Cu-MSNs led to robust osteogenic differentiation of bone mesenchymal stem cells (BMSCs) via the activation of Oncostation M (OSM) pathway. These results suggest that the novel Cu-MSNs could be used as an immunomodulatory agent with osteostimulatory capacity for bone regeneration/therapy application. Statement of significance In order to stimulate both osteogenesis and angiogenesis of stem cells for further bone regeneration, a new kind of hypoxia-inducing copper doped mesoporous silica nanospheres (Cu-MSNs) were prepared via one-pot synthesis. Biological assessments under immune environment which better reflect the in vivo response revealed that the nanospheres possessed osteostimulatory capacity and had potential as immunomodulatory agent for bone regeneration/therapy application. The strategy of introducing controllable amount of therapeutic ions instead of loading expensive drugs/growth factors in mesoporous silica nanosphere provides new options for bioactive nanomaterial functionalization.

Dielectric and electrical conductivity properties of multi-stage spark plasma sintered HA-CaTiO3 composites and comparison with conventionally sintered materials

One of the different issues limiting the wider application of monolithic hydroxyapatite (HA) as an ideal bone replacement material is the lack of reasonably good electrical transport properties. The comprehensive electrical property characterization to evaluate the efficacy of processing parameters in achieving the desired combination of electroactive properties is considered as an important aspect in the development of HA-based bioactive material. In this perspective, the present work reports the temperature (RT-200 degrees C) and frequency (100 Hz-1 MHz) dependent dielectric properties and AC conductivity for a range of HA-CaTiO3 (HA-CT) composites, densified using both conventional pressureless sintering in air as well as spark plasma sintering in vacuum. Importantly, the AC conductivity of spark plasma sintered ceramics similar to upto 10(-5) (Omega cm)(-1)] are found to be considerably higher than the corresponding pressureless sintered ceramics similar to upto 10(-8) (Omega cm)(-1)]. Overall, the results indicate the processing route dependent functional properties of HA-CaTiO3 composites as well as related advantages of spark plasma sintering route. (C) 2013 Elsevier Ltd. All rights reserved.

Flow Cytometry Analysis of Cytotoxicity In Vitro and Long-Term Toxicity of HA-40wt% BaTiO3 Nanoparticles In Vivo

The development of new implantable biomaterials requires bone-mimicking physical properties together with desired biocompatible property. In continuation to our earlier published research to establish compositional dependent multifunctional bone-like properties and cytocompatibility response of hydroxyapatite (HA)-BaTiO3 composites, the toxicological property evaluation, both invitro and invivo, were conducted on HA-40wt% BaTiO3 and reported in this work. In particular, this work reports invitro cytotoxicity of mouse myoblast cells as well as invivo long-term tissue and nanoparticles interaction of intra-articularly injected HA-40wt% BaTiO3 and BaTiO3 up to the concentration of 25mg/mL in physiological saline over 12weeks in mouse model. The careful analysis of flow cytometry results could not reveal any statistically significant difference in terms of early/late apoptotic cells or necrotic cells over 8d in culture. Extensive histological analysis could not record any signature of cellular level toxicity or pronounced inflammatory response in vital organs as well as at knee joints of Balb/c mice after 12weeks. Taken together, this study establishes nontoxic nature of HA-40wt% BaTiO3 and therefore, HA-40wt% BaTiO3 can be used safely for various biomedical applications.

The synthesis and characterization of nanophase hydroxyapatite using a novel dispersant-aided precipitation method

The synthesis of nanophase hydroxyapatite (nHA) is of importance in the field of biomaterials and bone tissue engineering. The bioactive and osteoconductive properties of nHA are of much benefit to a wide range of biomedical applications such as producing bone tissue engineered constructs, coating medical implants, or as a carrier for plasmid DNA in gene delivery. This study aimed to develop a novel low-temperature dispersant-aided precipitation reaction to produce nHA particles (

Three-Dimensional Characterization of Pores in Ti-6Al-4V Alloy

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

The effect of BMP-2 on the osteoconductive properties of beta-tricalcium phosphate in rat calvaria defects

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Biomimetic calcium phosphate coating on Ti-7.5Mo alloy for dental application

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Genetic Responses to Nanostructured Calcium-phosphate-coated Implants

Nanostructured calcium phosphate (CaP) has been histologically and biomechanically proven to enhance osseointegration of implants; however, conventional techniques were not sufficiently sensitive to capture its biological effects fully. Here, we compared the conventional removal torque (RTQ) evaluation and gene expression in tissues around nanostructured CaP-coated implants, using real-time RT-PCR, with those of uncoated implants, in a rabbit model. At 2 wks, RTQ values were significantly higher, alkaline phosphatase (ALP) expression was significantly higher, and runt-related transcription factor 2 and tumor necrosis factor-alpha expressions were significantly lower in the coated than in the uncoated implants. This indicates that inflammatory responses were suppressed and osteoprogenitor activity increased around the CaP-coated surface. At 4 wks, although RTQ values did not significantly differ between the 2 groups, ALP and osteocalcin (OCN) were significantly up-regulated in the coated group, indicating progressive mineralization of the bone around the implant. Moreover, an osteoclast marker, adenosine triphosphatase, which indicates acidification of the resorption lacunae, was significantly higher for the coated implants, suggesting gradual resorption of the CaP coating. This study reveals detailed genetic responses to nanostructured CaP-coated implants and provides evidence that the effect of nanotopography is significant during the osseointegration cascade.

Fibrin adhesive implant in wound healing repair of dental sockets with topical application of epsilon aminocaproic acid: Histological analysis

The aim of the study was to evaluate wound healing repair of dental sockets after topical application of 5% epsilon-aminocaproic acid (EACA) and the use of fibrin adhesive implant in rats under anticoagulant therapy with warfarin. Sixty Albinus wistar rats were used, divided into three groups of 20. In Group I, the animals were given 0.1 mL/100 mg of 0.9% saline solution per day, beginning 6 days before dental extraction and continuing throughout the experimental period. In Group II, the animals received 0.03 mL of sodium warfarin daily, beginning 6 days before the surgery and continuing until the day of sacrifice; after tooth extractions, the sockets were filled with fibrin adhesive material. In Group III the animals were treated as in Group II, and after extractions, the sockets were irrigated with 5 mL of 5% EACA and filled with the same fibrin adhesive material. All groups presented biological phases of wound healing repair, the differences being evident only in the chronology. The results obtained in Group III were very similar to those of Group I in the last period of wound repair, whereas Group II presented a late chronology compared to the other groups. © 2005 Wiley Periodicals, Inc.

Autogenous transplantation of rib cartilage preserved in glycerol, after removal of the perichondrium, to the malar process of rats--a histological study (Part I).

Seventy-two male albino rats received autogenous transplants of glycerol-preserved rib cartilage into the malar process. The animals were divided into two groups which received preserved cartilage with or without perichondrium. The implants were well tolerated and removal of the perichondrium enhanced the rate of resorption and bone replacement of the material.

Geometric modeling from the medical images in the CAD system to support prosthesis design

This paper presents an individual designing prosthesis for surgical use and proposes a methodology for such design through mathematical extrapolation of data from digital images obtained via tomography of individual patient's bones. Individually tailored prosthesis designed to fit particular patient requirements as accurately as possible should result in more successful reconstruction, enable better planning before surgery and consequently fewer complications during surgery. Fast and accurate design and manufacture of personalized prosthesis for surgical use in bone replacement or reconstruction is potentially feasible through the application and integration of several different existing technologies, which are each at different stages of maturity. Initial case study experiments have been undertaken to validate the research concepts by making dimensional comparisons between a bone and a virtual model produced using the proposed methodology and a future research directions are discussed.

A human retrieval study of plasma-sprayed hydroxyapatite-coated plateau root form implants after 2 months to 13 years in function

Calcium phosphate-based bioactive ceramics in various physical and chemical formulations have been extensively utilized as biomaterials for bone regeneration/conduction. However, the determination of their in vivo temporal behavior from the short to long term in humans has been a challenge due to the lack of physical reference for morphologic and morphometric evaluation. The present study evaluated bone morphology and morphometry (bone-to-implant contact [BIC]) around plasma-sprayed hydroxyapatite (PSHA)-coated endosseous implants that were retrieved due to prosthetic reasons while successfully in function at the posterior region of the jaws from as early as 2 months to ~13 years after a 6-month healing period after placement. Bone morphology was evaluated by light microscopy, and BIC was determined using computer software. Irrespective of the time in vivo, lamellar bone was observed in close contact with the implant PSHA-coated surface and between plateaus. BIC ranged from ~35-95%, was highly directional, and Haversian-like osteonic morphology between plateaus was observed for most implants. The PSHA coating was present with little variation in thickness between the samples retrieved regardless of time in vivo. © 2010 by Begell House, Inc.

Implant-abutment gap versus microbial colonization: Clinical significance based on a literature review

Microorganisms from the oral cavity may settle at the implant-abutment interface (IAI). As a result, tissue inflammation could occur around these structures. The databases MEDLINE/PubMed and PubMed Central were used to identify articles published from 1981 through 2012 related to the microbial colonization in the implant-abutment gap and its consequence in terms of crest bone loss and osseointegration. The following considerations could be put forward, with respect to the clinical importance of IAI: (a) the space present at the IAI seems to allow bacterial leakage to occur, in spite of the size of this space; (b) bacterial leakage seems to occur at the IAI, irrespective of the type of connection. More studies are necessary to clarify the relationship between leakage at IAI and abutment connection designs; (c) losses at the peri-implant bone crests cannot be related to the IAI size, since few studies have shown no relationship. Also, the microbial leakage at the IAI cannot be related to the bone crest loss, since there are no articles reporting this relationship; remains controversial the influence of the IAI position on the bone crest losses. © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 101B: 1321-1328, 2013. Copyright © 2013 Wiley Periodicals, Inc.