Search

Intervertebral disc (IVD) degeneration and herniation is a leading cause of disability globally and a large unmet clinical need. No efficient non-surgical therapy is available, and there is an urgency for minimally invasive therapies capable of restoring tissue function. IVD spontaneous hernia regression following conservative treatment is a clinically relevant phenomenon that has been linked to an inflammatory response. This study establishes the central role of macrophages in IVD spontaneous hernia regression and provides the first preclinical demonstration of a macrophage-based therapy for IVD herniation. A rat model of IVD herniation was used to test complementary experimental setups: (1) macrophage systemic depletion via intravenous administration of clodronate liposomes (Group CLP2w: depletion between 0 and 2 weeks post-lesion; Group CLP6w: depletion between 2 and 6 weeks post-lesion), and (2) administration of bone marrow-derived macrophages into the herniated IVD, 2 weeks post-lesion (Group Mac6w). Herniated animals without treatment were used as controls. The herniated area was quantified by histology in consecutive proteoglycan/collagen IVD sections at 2 and 6 weeks post-lesion. Clodronate-mediated macrophage systemic depletion was confirmed by flow cytometry and resulted in increased hernia sizes. Bone marrow-derived macrophages were successfully administered into rat IVD hernias resulting in a 44% decrease in hernia size. No relevant systemic immune reaction was identified by flow cytometry, cytokine, or proteomic analysis. Furthermore, a possible mechanism for macrophage-induced hernia regression and tissue repair was unveiled through IL4, IL17a, IL18, LIX, and RANTES increase. This study represents the first preclinical proof-of-concept of macrophage-based immunotherapy for IVD herniation. [ABSTRACT FROM AUTHOR]

Purpose: Over the last years, the number of vertebral arthrodesis has been steadily increasing. The use of iliac crest bone autograft remains the "gold standard" for bone graft substitute in these procedures. However, this solution has some side effects, such as the problem of donor site morbidity indicating that there is a real need for adequate alternatives. This pilot study aimed to evaluate the usefulness of chitosan (Ch) porous 3D scaffolds incorporated with resolvin D1 (RvD1) as an alternative implant to iliac bone autograft. Methods: We have performed bilateral posterolateral lumbar vertebral arthrodesis in a rat animal model. Three experimental groups were used: (i) non-operated animals; (ii) animals implanted with Ch scaffolds incorporated with RvD1 and (iii) animals implanted with iliac bone autograft. Results: The collagenous fibrous capsule formed around the Ch scaffolds with RvD1 is less dense when compared with the iliac bone autograft, suggesting an important anti-inflammatory effect of RvD1. Additionally, new bone formation was observed in the Ch scaffolds with RvD1. Conclusion: These results demonstrate the potential of these scaffolds for bone tissue repair applications. [ABSTRACT FROM AUTHOR]

Western blot images are representative of protein expression/phosphorylation status in distinct donors (at least I n i = 4), evaluated in two independent experiments." should read: "Ionizing radiation induces macrophage NF- B activation and increases Bcl-xL expression. As a result, the Figure 2 legend, "Ionizing radiation induces macrophage NF- B activation and increases Bcl-xL expression. [Extracted from the article]

The remarkable properties of poly-aminoacids, mainly their biocompatibility and biodegradability, have prompted an increasing interest in these polymers for biomedical applications. Poly-γ-glutamic acid (γ-PGA) is one of the most interesting poly-aminoacids with potential applications as a biomaterial. Here we describe the production and characterization of γ-PGA by Bacillus subtilis natto. The γ-PGA was produced with low molecular weight (10-50 kDa), high purity grade (>99 %) and a d-/ l-glutamate ratio of 50-60/50-40 %. To evaluate the feasibility of using this γ-PGA as a biomaterial, chitosan (Ch)/γ-PGA nanoparticles were prepared by the coacervation method at pH ranging from 3.0 to 5.0, with dimensions in the interval 214-221 nm with a poly-dispersion index of ca. 0.2. The high purity of γ-PGA produced by this method, which is firstly described here, renders this biopolymer suitable for biomedical applications. Moreover, the Ch/γ-PGA nanocomplexes developed in this investigation can be combined with biologically active substances for their delivery in the organism. The fact that the assembly between Ch and γ-PGA relies on electrostatic interactions enables addition of other molecules that can be released into the medium through changes from acidic to physiological pH, without loss in biological activity. [ABSTRACT FROM AUTHOR]

This study reports the use of tetraethylene glycol-terminated self-assembled monolayers (EG SAMs) as a background non-fouling surface to study the effect of an 18 carbon ligand (C18) on albumin selective and reversible adsorption and subsequent platelet and leukocyte adhesion. Surface characterization techniques revealed an efficient immobilization of different levels of C18 ligand on EG SAMs and an increase of surface thickness and hydrophobicity with the increase of C18 ligands. Albumin adsorption increased as the percentage of C18 ligands on the surface increased, but only 2.5%C18 SAMs adsorbed albumin in a selective and reversible way. Adherent platelets also increased with the amount of immobilized C18. Pre-immersion of samples in albumin before contact with platelets demonstrated an 80% decrease in platelet adhesion. Pre-immersion in plasma was only relevant for 2.5%C18 SAMs since this was the only surface to have less platelet adhesion compared to buffer pre-immersion. EG SAMs adhered negligible amounts of leukocytes, but surfaces with C18 ligands have some adherent leukocytes. Except for 10%C18 SAMs, which increased leukocyte adhesion after albumin pre-adhesion, protein pre-immersion did not influence leukocyte adhesion. It has been shown that a surface with a specific surface concentration of albumin-binding ligands (2.5%C18 SAMs) can recruit albumin selectively and reversibly and minimize the adhesion of platelets, despite still adhering some leukocytes. [ABSTRACT FROM AUTHOR]

A polymeric solution and a reinforcement phase can work as an injectable material to fill up bone defects. However, the properties of the solution should be suitable to enable the transport of that extra phase. Additionally, the use of biocompatible materials is a requirement for tissue regeneration. Thus, we intended to optimize a biocompatible polymeric solution able to carry hydroxyapatite microspheres into bone defects using an orthopedic injectable device. To achieve that goal, polymers usually regarded as biocompatible were selected, namely sodium carboxymethylcellulose, hydroxypropylmethylcellulose, and Na-alginate (ALG). The rheological properties of the polymeric solutions at different concentrations were assessed by viscosimetry before and after moist heat sterilization. In order to correlate rheological properties with injectability, solutions were tested using an orthopedic device applied for minimal invasive surgeries. Among the three polymers, ALG solutions presented the most suitable properties for our goal and a non-sterile ALG 6% solution was successfully used to perform preliminary injection tests of hydroxyapatite microspheres. Sterile ALG 7.25% solution was found to closely match non-sterile ALG 6% properties and it was selected as the optimal vehicle. Finally, sterile ALG 7.25% physical stability was studied at different temperatures over a 3-month period. It was observed that its rheological properties presented minor changes when stored at 25°C or at 4°C. [ABSTRACT FROM AUTHOR]

Osteoporosis is a systemic disease that results in loss of bone density and increased fracture risk, particularly in the vertebrae and the hip. This condition and associated morbidity and mortality increase with population ageing. Long noncoding (lnc) RNAs are transcripts longer than 200 nucleotides that are not translated into proteins, but play important regulatory roles in transcriptional and post-transcriptional regulation. Their contribution to disease onset and development is increasingly recognized. Herein, we present an integrative revision on the studies that implicate lncRNAs in osteoporosis and that support their potential use as therapeutic tools. Firstly, current evidence on lncRNAs involvement in cellular and molecular mechanisms linked to osteoporosis and its major complication, fragility fractures, is reviewed. We analyze evidence of their roles in osteogenesis, osteoclastogenesis, and bone fracture healing events from human and animal model studies. Secondly, the potential of lncRNAs alterations at genetic and transcriptomic level are discussed as osteoporosis risk factors and as new circulating biomarkers for diagnosis. Finally, we conclude debating the possibilities, persisting difficulties, and future prospects of using lncRNAs in the treatment of osteoporosis. Molecular biology: decoding the dark matter of osteoporosis Genomic 'dark matter' could improve the diagnosis and prognosis of patients with osteoporosis, as well as providing new drug targets for the disease. Only 2.3% of the human genome is translated into protein; the function of the remainder had been unclear, but recent studies suggest some of it provides instructions for making regulators of protein synthesis called long non-coding RNAs (lncRNAs). In this review, Maria Ines Almeida at the University of Porto in Portugal and colleagues explore the role of lncRNAs in bone cell differentiation, metabolism and fracture healing - and describe early studies assessing their role as diagnostic and prognostic biomarkers of osteoporosis. Future advances in genome editing may also provide opportunities to redress the balance between bone production and resorption – something that becomes skewed in osteoporosis - by targeting lncRNAs. [ABSTRACT FROM AUTHOR]

Mesenchymal Stem/Stromal Cells (MSC) are a promising cell type for cell-based therapies - from tissue regeneration to treatment of autoimmune diseases - due to their capacity to migrate to damaged tissues, to differentiate in different lineages and to their immunomodulatory and paracrine properties. Here, a simple and reliable imaging technique was developed to study MSC dynamical behavior in natural and bioengineered 3D matrices. Human MSC were transfected to express a fluorescent photoswitchable protein, Dendra2, which was used to highlight and follow the same group of cells for more than seven days, even if removed from the microscope to the incubator. This strategy provided reliable tracking in 3D microenvironments with different properties, including the hydrogels Matrigel and alginate as well as chitosan porous scaffolds. Comparison of cells mobility within matrices with tuned physicochemical properties revealed that MSC embedded in Matrigel migrated 64% more with 5.2 mg protein/mL than with 9.6 mg/mL and that MSC embedded in RGD-alginate migrated 51% faster with 1% polymer concentration than in 2% RGD-alginate. This platform thus provides a straightforward approach to characterize MSC dynamics in 3D and has applications in the field of stem cell biology and for the development of biomaterials for tissue regeneration. [ABSTRACT FROM AUTHOR]