Nanocellulose-based porous materials: Regulation and pathway to commercialization in regenerative medicine.

We review the recent progress that have led to the development of porous materials based on cellulose nanostructures found in plants and other resources. In light of the properties that emerge from the chemistry, shape and structural control, we discuss some of the most promising uses of a plant-based material, nanocellulose, in regenerative medicine. Following a brief discussion about the fundamental aspects of self-assembly of nanocellulose precursors, we review the key strategies needed for material synthesis and to adjust the architecture of the materials (using three-dimensional printing, freeze-casted porous materials, and electrospinning) according to their uses in tissue engineering, artificial organs, controlled drug delivery and wound healing systems, among others. For this purpose, we map the structure-property-function relationships of nanocellulose-based porous materials and examine the course of actions that are required to translate innovation from the laboratory to industry. Such efforts require attention to regulatory aspects and market pull. Finally, the key challenges and opportunities in this nascent field are critically reviewed.

Cancer Inhibition and In Vivo Osteointegration and Compatibility of Gallium-Doped Bioactive Glasses for Osteosarcoma Applications.

Traditional osteosarcoma therapies tend to focus solely on eradicating residual cancer cells and often fail to promote local bone regeneration and even inhibit it due to lack of precise control over target cells, i.e., the treatment affects both normal and cancer cells. Typically, multistep procedures are required for optimal efficacy. Here, we found that a silica-based bioactive material containing 3 mol % gallium oxide selectively kills human osteosarcoma cells and presents excellent in vivo osteointegration, while showing no local or systemic toxicity. Cell culture media conditioned with the proposed material was able to kill 41% of osteosarcoma cells, and no significant deleterious effect on normal human osteoblasts was observed. In addition, rats treated with the gallium-doped material showed excellent material-bone integration with no sign of local toxicity or implant rejection. Systemic biocompatibility investigation did not indicate any sign of toxicity, with no presence of fibrosis or cellular infiltrate in the histological microstructure of the liver and kidneys after 56 days of observation. Taken together, these results show that synergistic bone regeneration and targeted cancer therapy can be combined, paving the way toward new bone cancer treatment approaches.

In vitro and in vivo osteogenic potential of niobium-doped 45S5 bioactive glass: A comparative study.

In vitro and in vivo experiments were undertaken to evaluate the solubility, apatite-forming ability, cytocompatibility, osteostimulation, and osteoinduction for a series of Nb-containing bioactive glass (BGNb) derived from composition of 45S5 Bioglass. Inductively coupled plasma optical emission spectrometry (ICP-OES) revealed that the rate at which Na, Ca, Si, P, and Nb species are leached from the glass decrease with the increasing concentration of the niobium oxide. The formation of apatite as a function of time in simulated body fluid was monitored by 31P Magic Angle Spinning (MAS) Nuclear magnetic resonance spectroscopy. Results showed that the bioactive glasses: Bioglass 45S5 (BG45S5) and 1 mol%-Nb-containing-bioactive glass (BGSN1) were able to grow apatite layer on their surfaces within 3 h, while glasses with higher concentrations of Nb2 O5 (2.5 and 5 mol%) took at least 12 h. Nb-substituted glasses were shown to be compatible with bone marrow-derived mesenchymal stem cells (BMMSCs). Moreover, the bioactive glass with 1 mol% Nb2 O5 significantly enhanced cell proliferation after 4 days of treatment. Concentrations of 1 and 2.5 mol% Nb2 O5 stimulated osteogenic differentiation of BMMSCs after 21 days of treatment. For the in vivo experiments, trial glass rods were implanted into circular defects in rat tibia in order to evaluate their osteoconductivity and osteostimulation. Two morphometric parameters were analyzed: (a) thickness of new-formed bone layer and (b) area of new-formed subperiostal bone. Results showed that BGNb bioactive glass is osteoconductive and osteostimulative. Therefore, these results indicate that Nb-substituted glass is suitable for biomedical applications.

Evaluation of effectiveness of 45S5 bioglass doped with niobium for repairing critical-sized bone defect in in vitro and in vivo models.

Here, we investigated the biocompatibility of a bioactive sodium calcium silicate glass containing 2.6 mol% Nb2 O5 (denoted BGPN2.6) and compare the results with the archetypal 45S5 bioglass. The glass bioactivity was tested using a range of in vitro and in vivo experiments to assess its suitability for bone regeneration applications. in vitro studies consisted of assessing the cytocompatibility of the BGPN2.6 glass with bone-marrow-derived mesenchymal stem cells (BM-MSCs). Systemic biocompatibility was verified by means of the quantification of biochemical markers and histopathology of liver, kidneys, and muscles. The glass genotoxicity was assessed using the micronucleus test. The regeneration of a calvarial defect was assessed using both qualitative and quantitative analysis of three-dimensional microcomputed tomography images. The BGPN2.6 glass was not cytotoxic to BM-MSCs. It is systemically biocompatible causing no signs of damage to high metabolic and excretory organs such as the liver and kidneys. No mutagenic potential was observed in the micronucleus test. MicroCT images showed that BGPN2.6 was able to nearly fully regenerate a critical-sized calvarial defect and was far superior to standard 45S5 Bioglass. Defects filled with BGPN2.6 glass showed over 90% coverage compare to just 66% for 45S5 Bioglass. For one animal the defect was completely filled in 8 weeks. These results clearly show that Nb-containing bioactive glasses are a safe and effective biomaterial for bone replacement.

Nanocellulose/bioactive glass cryogels as scaffolds for bone regeneration.

A major challenge exists in the preparation of scaffolds for bone regeneration, namely, achieving simultaneously bioactivity, biocompatibility, mechanical performance and simple manufacturing. Here, cellulose nanofibrils (CNF) are introduced for the preparation of scaffolds taking advantage of their biocompatibility and ability to form strong 3D porous networks from aqueous suspensions. CNF are made bioactive for bone formation through a simple and scalable strategy that achieves highly interconnected 3D networks. The resultant materials optimally combine morphological and mechanical features and facilitate hydroxyapatite formation while releasing essential ions for in vivo bone repair. The porosity and roughness of the scaffolds favor several cell functions while the ions act in the expression of genes associated with cell differentiation. Ion release is found critical to enhance the production of the bone morphogenetic protein 2 (BMP-2) from cells within the fractured area, thus accelerating the in vivo bone repair. Systemic biocompatibility indicates no negative effects on vital organs such as the liver and kidneys. The results pave the way towards a facile preparation of advanced, high performance CNF-based scaffolds for bone tissue engineering.

Avaliação da aplicação de ondas de ultra-som sobre cimentos de ionômero de vidro: rugosidade superficial e dureza / Evoluation of ultrasonic waves application on glass ionomer cements: superficial roughness and hardness

A aplicação de ondas ultra-sônicas durante a reação de presa inicial do cimento de ionômero de vidro (CIV) tem demonstrado aumento da velocidade de cura, diminuição da incorporação de bolhas de ar e melhora em algumas propriedades mecânicas. O objetivo deste estudo foi avaliar o efeito do ultra-som sobre a microdureza e a rugosidade superficial de dois CIVs (FUJI IX GP-GC Corporation e o Ketac Molar EasyMix- 3M ESPE). Foram confeccionados quarenta corpos de prova, sendo vinte para a avaliação da rugosidade superficial e vinte para avaliação da microdureza, e metade deles recebeu por trinta segundos a aplicação de ondas de ultra-som. As leituras da rugosidade superficial foram realizadas antes e após o ensaio de escovação. Os vinte corpos de prova restantes foram polidos com lixas abrasivas de granulações decrescentes e submetidos ao teste de dureza, utilizando um durômetro digital equipado com diamante Knoop. Os resultados, analisados pela análise de variância (ANOVA) (p<0,05), demonstraram aumento da dureza para todos os grupos com a aplicação de ondas de ultra-som, sendo maior para o Ketac Molar EasyMix. A aplicação de ultra-som causou também diminuição significativa da rugosidade superficial para o Ketac Molar EasyMix. Após o ensaio de escovação, esta última propriedade aumentou para todos os materiais. Pôde-se concluir que a aplicação de ondas de ultra-som foi efetiva em aumentar a dureza superficial dos materiais e que melhorou a rugosidade do Ketac Molar EasyMix antes do ensaio de escovação.

The application of ultrasonic waves during the initial setting of the glass ionomer cements (GIC) has demonstrated increase of the cure speed, reduction of air bubbles and improves in some mechanical properties. The aim of this study was to evaluate the effect of the ultrasound on the microhardness and the superficial roughness in two GICs (FUJI IX GP (GC Corporation) and Ketac Molar EasyMix (3M ESPE)). Forty specimens were confectioned, twenty for evaluation of the superficial roughness and twenty for evaluation of the microhardness. Half of them received for thirty seconds the ultrasonic waves application. The readings of the roughness had been carried before and after the toothbrushing test. The twenty remaining specimens had been polished with abrasive sandpapers of decreasing granulations and submitted to the hardness test. The results, analyzed for the variance analysis (ANOVA) (p<0,05), had demonstrated increase of the hardness for all the groups with the application of ultrasonic waves, being bigger for the Ketac Molar Easy-Mix. The ultrasound application also caused significant reduction of the superficial roughness for the Ketac Molar EasyMix. After the toothbrushing test, this last property increased for all the materials. It could be concluded that the application of ultrasonic waves was effective in increasing the superficial hardness of the materials and that it improved the roughness of the Ketac Molar EasyMix before the toothbrushing test.

Incorporation of mineral phosphorus and potassium on leather waste (collagen): a new N(collagen)PK-fertilizer with slow liberation.

The feasibility of using a solid waste (rich in nitrogen) from the leather industry, after chromium extraction, as adsorbent for P and K, for possible utilization as NPK fertilizer was evaluated. The materials, with and without the addition of P and K, were characterized by chemical analyses, infrared spectroscopy, EDS (energy dispersive X-ray spectrometry) and SEM (scanning electronic microscopy). Langmuir and Freundlich equations were used for analyzing the experimental data, which showed a better fit to the Freundlich model, thus suggesting a multilayer adsorption process on the surface of the adsorbent. A preliminary test in greenhouse demonstrates that the P and K incorporation on the matrix rich in nitrogen (collagen) is a interesting alternative to use such material as NPK fertilizer. The application of N(collagen)PK formulations, as a source of nutrients for the growth of rice plants, showed promising agronomic results.