Effects of latex membrane on guided regeneration of long bones

Abstract

Natural latex extracted from Hevea brasiliensis is one of the materials pointed out as potential tissue regenerators. The use of latex-based membranes in bone regeneration might be an alternative to stimulate bone formation. The aim of this study was to evaluate the effects of latex membranes in guided bone regeneration of defects produced in long bones of rats. Sixty rats were equally divided into latex and control groups, and each group was subdivided into two subgroups according to treatment duration of 1 and 4 weeks. Bone defects with 2.5?mm in diameter were surgically made in the left tibia. In the animals of the latex group, a latex membrane was placed over the bone defect. The samples underwent quantitative histological analysis of bone formation and collagen matrix, immunohistochemical analysis of osteogenic protein markers, assessment of bone mechanical properties and bone densitometry, and radiological assessment. The osteocalcin immunostaining data were submitted to the generalized linear model test with two independent factors. For the other data, the multivariate ANOVA with two independent factors was performed. The use of the latex membrane significantly improved (p?<?0.005) the volume of newly formed bone, collagen type I matrix, expression of osteopontin, and bone stiffness, both in the early and late stages of regeneration. In conclusion, the latex membrane was able to promote bone regeneration in long bones.     

Chronic inflammatory demyelinating polyradiculoneuropathy: A role for haematopoietic stem cell transplantation?

Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is a clinical syndrome of a chronic progressive or relapsing and remitting, symmetrical, sensory and motor radiculoneuropathy. The immune reaction in CIDP is characterised by selective inflammation of peripheral nerves and is probably due to the interaction of cellular and humoral responses. Only three treatments for CIDP have demonstrated benefit in randomised studies, corticosteroids, plasma exchange and intravenous immunoglobulin. 25% of patients fail to respond or do not respond adequately to these treatments. Experimental data in animal models have shown that several autoimmune disorders, either congenital or acquired, can be transferred and/or treated by the transplantation of bone marrow stem cells. Haematopoietic stem cell transplantation (HSCT) has been performed with varying success in over 700 patients with autoimmune disorders throughout Europe. The experience in CIDP is very limited. This article will review current understanding of CIDP and experience of the use of HSCT in refractory CIDP.     

Balancing mechanical strength with bioactivity in chitosan–calcium phosphate 3D microsphere scaffolds for bone tissue engineering: air- vs. freeze-drying processes

The objective of this study was to evaluate the potential benefit of 3D composite scaffolds composed of chitosan and calcium phosphate for bone tissue engineering. Additionally, incorporation of mechanically weak lyophilized microspheres within those air-dried (AD) was considered for enhanced bioactivity. AD microsphere, alone, and air- and freeze-dried microsphere (FDAD) 3D scaffolds were evaluated in vitro using a 28-day osteogenic culture model with the Saos-2 cell line. Mechanical testing, quantitative microscopy, and lysozyme-driven enzymatic degradation of the scaffolds were also studied. FDAD scaffold showed a higher concentration (p?<?0.01) in cells per scaffold mass vs. AD constructs. Collagen was ～31% greater (p?<?0.01) on FDAD compared to AD scaffolds not evident in microscopy of microsphere surfaces. Alternatively, AD scaffolds demonstrated a superior threefold increase in compressive strength over FDAD (12 vs. 4?MPa) with minimal degradation. Inclusion of FD spheres within the FDAD scaffolds allowed increased cellular activity through improved seeding, proliferation, and extracellular matrix production (as collagen), although mechanical strength was sacrificed through introduction of the less stiff, porous FD spheres.     

Abaloparatide in patients with mild or moderate renal impairment: results from the ACTIVE phase 3 trial

Abstract

Objective: To evaluate, post hoc, the efficacy and safety of abaloparatide by degree of renal impairment.

Methods: ACTIVE was a phase 3, 18-month, randomized, double-blind, active-comparator, placebo-controlled study of postmenopausal women with osteoporosis who received subcutaneous abaloparatide 80?µg, placebo, or open-label teriparatide 20?µg daily. Patients with serum creatinine >2.0?mg/dL or 1.5–2.0?mg/dL with an estimated glomerular filtration rate (eGFR) <37?mL/min, calculated by Cockcroft-Gault formula, were excluded.

Results: At baseline, 660 patients had eGFR ≥90?mL/min, 1276 had 60 to ?90?mL/min, and 527 had <60?mL/min. Older age and lower T-scores were associated with greater renal impairment. Among renal-function subgroups, there were no meaningful changes in bone mineral density, fracture risk reduction, or overall incidence of treatment-emergent adverse events in the active-treatment arms. Anemia, nausea, hypercalcemia, and upper-respiratory-tract infection tended to be more frequent with increasing renal impairment. Hypercalcemia measured by albumin-adjusted serum calcium occurred significantly less frequently with abaloparatide than teriparatide in patients with eGFR <60?mL/min (3.6% versus 10.9%; p?=?.008) and in the overall ACTIVE safety population (3.4% versus 6.4%; p?=?.006). Computed tomography scans in 376 patients revealed no evidence of increased renal calcification.

Conclusion: Increased exposure to abaloparatide and teriparatide in patients with renal impairment led to no meaningful differences in efficacy or safety. These results support the use of abaloparatide without dosage adjustment in patients with renal impairment, provided those with severe renal impairments are monitored for adverse events.     

Inhaled formaldehyde induces DNA–protein crosslinks and oxidative stress in bone marrow and other distant organs of exposed mice

Formaldehyde (FA), a major industrial chemical and ubiquitous environmental pollutant, has been classified as a leukemogen. The causal relationship remains unclear, however, due to limited evidence that FA induces toxicity in bone marrow, the site of leukemia induction, and in other distal organs. Although induction of DNA–protein crosslinks (DPC), a hallmark of FA toxicity, was not previously detected in the bone marrow of FA‐exposed rats and monkeys in studies published in the 1980s, our recent studies showed increased DPC in the bone marrow, liver, kidney, and testes of exposed Kunming mice. To confirm these preliminary results, in the current study we exposed BALB/c mice to 0, 0.5, 1.0, and 3.0 mg m^?3 FA (8 hr per day, for 7 consecutive days) by nose‐only inhalation and measured DPC levels in bone marrow and other organs of exposed mice. As oxidative stress is a potential mechanism of FA toxicity, we also measured glutathione (GSH), reactive oxygen species (ROS), and malondialdehyde (MDA), in the bone marrow, peripheral blood mononuclear cells, lung, liver, spleen, and testes of exposed mice. Significant dose‐dependent increases in DPC, decreases in GSH, and increases in ROS and MDA were observed in all organs examined (except for DPC in lung). Bone marrow was among the organs with the strongest effects for DPC, GSH, and ROS. In conclusion, exposure of mice to FA by inhalation induced genotoxicity and oxidative stress in bone marrow and other organs. These findings strengthen the biological plausibility of FA‐induced leukemogenesis and systemic toxicity. Environ. Mol. Mutagen. 54:705–718, 2013. © 2013 Wiley Periodicals, Inc.     

Simvastatin delivery on PEEK for bioactivity and osteogenesis enhancements

Abstract

A strategy developed for obtaining positive cellular responses remains to be focused in the filed of functional biomimetics. In this study, a hydrogel covered simvastatin-loaded polyetheretherketone (PEEK) bio-composites was constructed with the purpose of bone tissue regeneration therapy. Briefly, a three-dimensional (3D) porous structure was fabricated on PEEK surface; then the substrate was functionalized with the poly(L-lactic acid)/simvastatin porous film and hyaluronic acid hydrogel subsequently. In vitro cell attachment, proliferation, and cytoskeletal observation experiments reveal that our scaffolds show better bio-affinity due to the layer of hyaluronic acid hydrogel compared with control. Furthermore, the alkaline phosphatase activity, calcium mineral deposition evaluation, and gene expression for osteogenic potential all exhibit that the superior osteogenic differentiation of MC3T3-E1 pre-osteoblasts on our scaffolds. Therefore, our PEEK samples loaded with simvastatin and covered with hyaluronic acid hydrogel hold great potential in clinical applications for bone repair.     

Rat Osteoclast Precursors In Vivo Express a Vitronectin Receptor and a Chloride-Bicarbonate Exchanger

In vivo osteoclast precursors, which are mononuclear, were previously found to express TRAP (tartrate-resistant acid phosphatase) and CTR (calcitonin receptor), like multi-nucleated osteoclasts. In vitro, they were found to express, in addition, VNR (vitronectin receptor) and CBE (chloride-bicarbonate exchanger). In order to ascertain that osteoclast precursors in vivo express VNR and CBE like their in vitro counterparts, we used immunohistochemistry to localize these molecules in developing long bones of neonatal rats. Frozen sections of metatarsals and phalanges of 1-2 day-old rats were stained for TRAP and mineralization using histochemistry or were reacted with polyclonal antibodies specific for either the β₃ chain of the VNR or synthetic sequences of the CBE. Both mature, multinucleated osteoclasts within the forming marrow cavity of metatarsals (as shown previously) and mononuclear osteoclast precursors located outside the bony collar of the phalangeal calcified rudiment (as shown here for the first time) expressed both TRAP, VNR and CBE. These findings suggest that mononuclear osteoclast precursors express many of the phenotypical markers of multinucleated osteoclasts prior to their fusion and multinucleation which may allow them to resorb bone, as suggested by in vitro observations of pit formation by preosteoclasts cultured on resorbable substances.     

The effect of an intramedullary biodegradable self-reinforced polyglycolic acid implant on tubular bone. An experimental study on growing dogs

The purpose of this study was to examine the effects of intramedullary self-reinforced polyglycolic acid (SR-PGA) implant to the femoral bone growth in a growing dog by using radiographic, microradiographic, oxytetracycline-fluorescence, histological, polariscopical and histomorphometric studies. Intramedullary reaming and SR-PGA implant did not cause any longitudinal overgrowth phenomenon, but resulted in a slight increase in femoral neck-angle. The bone histology showed normal features and blood cell counts were within normal limits.     

Towards a better understanding of bone bridge formation in the growth plate – an immunohistochemical approach

Abstract

The growth plate at the end of long bones is the cartilaginous organ responsible for longitudinal bone growth in children. Trauma to the growth plate, i.e. fractures, can severely impair longitudinal bone growth, leading to growth disorders due to destruction of the epiphyseal circulation and formation of a bone bridge. From the clinical experience it is known that in some patients this bone bridge eventually disappears during the growth process. However, the molecular mechanisms involved in bone bridge formation and dissolution have not been clarified yet. The aim of this study was to investigate the spatial and temporal protein level of molecules potentially involved in these processes, i.e. RANKL, OPG, DKK-1, Coll 10, BMP-2 and IL-6, in an experimental rat model using an immunohistochemical approach. The results from our study suggest that bone bridge formation might be an early event starting immediately after growth plate injury and involving several pro-osteoblastic molecules, i.e. IL-6, BMP-2 as well as OPG and Coll X. In the late studied time points 3- and 9-month post-injury expression of anti-osteoblastic proteins, i.e. DKK1 and RANKL, was increased. This indicates that bone bridge dissolution might be a late event and potentially linked to Wnt signaling inhibition and RANK/RANKL signaling activation.