The repair of large bone defects such as segmental defects in

The repair of large bone defects such as segmental defects in the long bones of the limbs is a challenging clinical problem. enhanced new bone formation to 46% 57 and 45% respectively. New bone formation in scaffolds pretreated for 1 3 and 6 days and loaded with bone morphogenetic protein-2 (BMP-2) (1 μg/defect) was 65% 61 and 64% respectively. The results show that converting a surface layer of the glass to hydroxyapatite or loading the surface-treated scaffolds with BMP-2 can significantly improve the capacity of 13-93 bioactive glass scaffolds to regenerate bone in an osseous defect. Based on their mechanical properties evaluated previously and their capacity to regenerate bone found in this study these CPI-203 13-93 bioactive glass scaffolds pretreated or loaded with BMP-2 are promising in structural bone repair. Keywords: bone regeneration bioactive glass scaffold surface modification bone morphogenetic protein-2 rat calvarial defect model 1 Introduction The repair of large bone defects is a challenging clinical problem [1]. While contained bone defects are repairable with commercially-available osteoconductive and osteoinductive filler materials [2 3 there is no ideal biological solution to reconstitute structural bone loss such as segmental defects in the long bones of the limbs. Available treatments such as bone allografts autografts porous metals and bone cement have limitations related to costs availability longevity donor site morbidity and uncertain healing to host bone. Consequently there is a great need for porous biocompatible implants that can replicate the structure and function of bone and have the requisite mechanical properties for reliable long-term cyclical loading during weight bearing. As described previously [4-6] bioactive glasses have several attractive properties as a scaffold material for bone repair such as their biocompatibility ability to convert in vivo to hydroxyapatite (the mineral constituent of bone) and ability to bond strongly to hard CPI-203 tissue. Some bioactive glasses such as the silicate glass designated 45S5 also have the ability to bond to soft tissue [5 6 Most previous studies have targeted bioactive glass scaffolds with relatively low strength three-dimensional (3D) architectures such as strengths in the range of human trabecular bone (2-12 MPa) [7]. Recent studies have shown that silicate bioactive glass scaffolds (13-93 and 6P53B) created by solid freeform fabrication techniques such as freeze extrusion fabrication [8] and robocasting [9 10 have compressive strengths (~140 MPa) comparable to human cortical bone (100-150 MPa) [7]. Our recent work showed that strong porous bioactive glass (13-93) scaffolds created using robocasting had excellent mechanical reliability (Weibull modulus = 12) and promising fatigue resistance under cyclic CPI-203 stresses far greater than normal physiological stresses [11] but the capacity of those strong porous bioactive glass (13-93) scaffolds to regenerate bone has not yet been studied. Our recent studies also showed that the elastic (brittle) mechanical response of the 13-93 bioactive glass scaffolds in vitro changed to an “elasto-plastic” response after implantation for longer than 2-4 weeks in vivo as a result of soft and hard tissue growth into the pores of the scaffolds [11 12 However concerns still remain about the low fracture toughness flexural strength and torsional strength of the as-fabricated bioactive glass scaffolds. In addition to material composition and microstructure [13] scaffold healing to bone in vivo can be markedly affected by other variables such as surface composition and structure the release of osteoinductive growth factors and the presence (or absence) of living cells. Interconnected pores of size 100 μm are recognized as the minimum requirement for supporting Rabbit Polyclonal to GPR132. tissue ingrowth [14] but pores of size 300 μm or larger may be required for enhanced bone ingrowth and capillary formation [15]. Surface modification of macroporous bioactive glass scaffolds have targeted the creation of fine pores (nanometers to a few microns in size) to modify the surface roughness and increase the surface area of the scaffolds [16-18]. Conversion of a surface layer to HA by reaction in an aqueous phosphate solution has been shown to improve the capacity of borate and silicate CPI-203 bioactive glass to support cell.

Background Systemic juvenile idiopathic arthritis (sJIA) is commonly considered an autoinflammatory

Background Systemic juvenile idiopathic arthritis (sJIA) is commonly considered an autoinflammatory disease. patients experienced ANA titers?≥?1:80 at diagnosis with 22/32 patients showing rising ANA titers with titers?≥?1:80 at PI3k-delta inhibitor 1 last follow-up (p =0.001). 10/32 patients experienced a positive RF at least once during follow-up compared to 0/32 at diagnosis (p?=?0.001). In 5/10 patients positive RF was documented at least twice more than twelve weeks apart. PI3k-delta inhibitor 1 Patients treated with TNF antagonists were not significantly more likely to develop positive ANA titers (p?=?0.425) or positive RF (p?=?0.703). Conclusions Patients with sJIA developed increased Rabbit Polyclonal to PARP4. ANA titers and positive RF over the course of the disease impartial of treatment with TNF antagonists. This might point towards an autoimmune rather than an autoinflammatory phenotype later in the course of sJIA. Keywords: Juvenile systemic arthritis Juvenile idiopathic arthritis Antinuclear antibodies Rheumatoid factor – autoimmunity Findings Introduction Systemic juvenile idiopathic arthritis (sJIA) is a disease characterized by marked systemic inflammation and a high rate of severe and potentially life-threatening manifestations. While categorized as a subtype of juvenile idiopathic arthritis (JIA) according to the ILAR-criteria sJIA is currently considered to represent an autoinflammatory rather than an autoimmune syndrome [1-3]. Autoinflammatory conditions are thought to symbolize abnormalities of the innate immune system with hallmark findings of seemingly unprovoked inflammation in contrast to autoimmune conditions caused by autoreactive T or B lymphocytes and autoantibodies. This might be an oversimplification since features of both autoinflammation and autoimmunity are typically present in most conditions; hence a classification of disorders along an axis PI3k-delta inhibitor 1 between autoinflammation and autoimmunity has been proposed [2 4 Although in sJIA systemic inflammation tends to decrease over time in most patients approximately half of sJIA patients can be expected to develop an aggressive polyarthritis [5]. This course of sJIA prospects to a phenotype of chronic polyarthritis similar to that observed in other forms of JIA in which autoimmunity appears to play an important role. The objective of this study was to determine frequencies of ANA and RF as circumstantial markers for autoimmunity in patients with sJIA over the course of the disease. Methods Patient sera and clinical data were acquired from your AID-Net database ( http://www.aid-register.de) a German registry and biobank that prospectively collects information and biomaterials of patients with autoinflammatory syndromes including periodic fevers syndromes and sJIA [6]. A single center sample of all patients with sJIA at the German Center for Pediatric and Adolescent Rheumatology was screened between January 2010 and July 2012 and all sJIA patients with a follow-up of more than one year were included. A retrospective chart survey was used to extract demographic data clinical course including total joint count and treatment as well as presence and titers of antinuclear antibodies (ANA) and rheumatoid factor (RF) at beginning and during follow-up. All ANA and RF studies were PI3k-delta inhibitor 1 performed in a single laboratory to ensure comparability and the laboratory methods were used consistently during the PI3k-delta inhibitor 1 follow-up period. ANA titers were decided using the HEp-2000 fluorescent ANA-Ro test system (Immuno Concepts Sacramento USA) and rheumatoid factors were decided using the Rheuatoid Factors II test kit with a cobas c 311 analyzer (Roche PI3k-delta inhibitor 1 Diagnostics GmbH Mannheim Germany). Analysis was performed using descriptive statistics Student’s T-Test/Fischer’s Exact test one-way ANOVA (ANA-positive ANA-negative patients and ANA-converted patients) and Spearman’s correlation (ANA-titers and total active joint count). Statistical analysis was performed with SPSS version 21.0 (SPSS Inc. Chicago USA). Results 32 patients were included in the study (20 of these female) with a median age at diagnosis of 4.2?years (range 0.5 – 11.4?years). The median follow-up was 6.0?years (range 1.1 – 17.3?years). During the course of disease 96.8% were treated with.