In Vitro Evaluation of Biphasic Calcium Phosphate Scaffolds Derived from Cuttlefish Bone Coated with Poly(ester urea) for Bone Tissue Regeneration.

This study investigates the osteogenic differentiation of umbilical-cord-derived human mesenchymal stromal cells (hUC-MSCs) on biphasic calcium phosphate (BCP) scaffolds derived from cuttlefish bone doped with metal ions and coated with polymers. First, the in vitro cytocompatibility of the undoped and ion-doped (Sr2+, Mg2+ and/or Zn2+) BCP scaffolds was evaluated for 72 h using Live/Dead staining and viability assays. From these tests, the most promising composition was found to be the BCP scaffold doped with strontium (Sr2+), magnesium (Mg2+) and zinc (Zn2+) (BCP-6Sr2Mg2Zn). Then, samples from the BCP-6Sr2Mg2Zn were coated with poly(ԑ-caprolactone) (PCL) or poly(ester urea) (PEU). The results showed that hUC-MSCs can differentiate into osteoblasts, and hUC-MSCs seeded on the PEU-coated scaffolds proliferated well, adhered to the scaffold surfaces, and enhanced their differentiation capabilities without negative effects on cell proliferation under in vitro conditions. Overall, these results suggest that PEU-coated scaffolds are an alternative to PCL for use in bone regeneration, providing a suitable environment to maximally induce osteogenesis.

Highly Porous Composite Scaffolds Endowed with Antibacterial Activity for Multifunctional Grafts in Bone Repair.

The present study deals with the development of multifunctional biphasic calcium phosphate (BCP) scaffolds coated with biopolymers-poly(ε-caprolactone) (PCL) or poly(ester urea) (PEU)-loaded with an antibiotic drug, Rifampicin (RFP). The amounts of RFP incorporated into the PCL and PEU-coated scaffolds were 0.55 ± 0.04 and 0.45 ± 0.02 wt%, respectively. The in vitro drug release profiles in phosphate buffered saline over 6 days were characterized by a burst release within the first 8h, followed by a sustained release. The Korsmeyer-Peppas model showed that RFP release was controlled by polymer-specific non-Fickian diffusion. A faster burst release (67.33 ± 1.48%) was observed for the PCL-coated samples, in comparison to that measured (47.23 ± 0.31%) for the PEU-coated samples. The growth inhibitory activity against Escherichia coli and Staphylococcus aureus was evaluated. Although the RFP-loaded scaffolds were effective in reducing bacterial growth for both strains, their effectiveness depends on the particular bacterial strain, as well as on the type of polymer coating, since it rules the drug release behavior. The low antibacterial activity demonstrated by the BCP-PEU-RFP scaffold against E. coli could be a consequence of the lower amount of RFP that is released from this scaffold, when compared with BCP-PCL-RFP. In vitro studies showed excellent cytocompatibility, adherence, and proliferation of human mesenchymal stem cells on the BCP-PEU-RFP scaffold surface. The fabricated highly porous scaffolds that could act as an antibiotic delivery system have great potential for applications in bone regeneration and tissue engineering, while preventing bacterial infections.

Surface functionalization of cuttlefish bone-derived biphasic calcium phosphate scaffolds with polymeric coatings.

Cuttlefish bone (CB) has been explored as biomaterial in the bone tissue-engineering field due to its unique porous structure and capacity of the aragonite mineral to be hydrothermally converted into calcium phosphates (CaPs). In the present study, undoped and ion (Sr2+, Mg2+ and/or Zn2+) doped biphasic calcium phosphate (BCP) scaffolds were prepared by hydrothermal transformation (HT, 200 °C, 24 h) of CB. The obtained scaffolds were sintered and then coated with two commercial polymers, poly(ε-caprolactone) (PCL) or poly(DL-lactide) (PDLA), and with two synthesized ones, a poly(ester amide) (PEA) or a poly(ester urea) (PEU) in order to improve their compressive strength. The scaffolds were characterized by X-ray diffraction (XRD) coupled with structural Rietveld refinement, Fourier transform infrared (FTIR) spectroscopy, and scanning electron microscopy (SEM). The results demonstrate that CB could be entirely transformed into BCPs in the presence or absence of doping elements. The initial CB structure was preserved and the polymeric coatings did not jeopardize the interconnected porous structure. Furthermore, the polymeric coatings enhanced the compressive strength of the scaffolds. The in vitro bio-mineralization upon immersing the scaffolds into simulated body fluid (SBF) demonstrated the formation of bone-like apatite surface layers in both uncoated and coated scaffolds. Overall, the produced scaffolds exhibit promising properties for bone tissue engineering applications.

Cuttlefish Bone-Derived Biphasic Calcium Phosphate Scaffolds Coated with Sol-Gel Derived Bioactive Glass.

The combination of calcium phosphates with bioactive glasses (BG) has received an increased interest in the field of bone tissue engineering. In the present work, biphasic calcium phosphates (BCP) obtained by hydrothermal transformation of cuttlefish bone (CB) were coated with a Sr-, Mg- and Zn-doped sol-gel derived BG. The scaffolds were characterized by X-ray diffraction, Fourier transform infrared spectroscopy and scanning electron microscopy. The initial CB structure was maintained after hydrothermal transformation (HT) and the scaffold functionalization did not jeopardize the internal structure. The results of the in-vitro bioactivity after immersing the BG coated scaffolds in simulated body fluid (SBF) for 15 days showed the formation of apatite on the surface of the scaffolds. Overall, the functionalized CB derived BCP scaffolds revealed promising properties, but further assessment of the in-vitro biological properties is needed before being considered for their use in bone tissue engineering applications.

Chitosan and polyethylene glycol based membranes with antibacterial properties for tissue regeneration.

The prevention of microbial infections associated with implantable medical devices and superficial wounds represents one of the main research strategies in the field of biomaterials. The present study reports on the development of composite membranes of Chitosan (CS)-Polyethylene glycol (PEG) matrix, incorporating particles of biphasic calcium phosphate (BCP), zinc oxide (ZnO) and copper oxide (CuO). The properties that are relevant for intended applications in tissue regeneration and antibacterial coatings of implants were assessed. It was found that the addition of 1% (w/w - relative to the mass of CS) of each metal oxide promoted satisfactory bacteriostatic activity and exhibited no cytotoxic effects towards the Vero cell line. The formation of bonds between the CS/PEG matrix and ionic species from the powders enhanced the cross-linking degree and mechanical properties of composite membranes in comparison to the non-doped membrane with the same polymer matrix (CS/PEG = 70/30%). A gradual degradation of the composite membranes over the immersion time in simulated body fluid (SBF) was accompanied by a continuous surface deposition of uniform apatite layer.

Synthetic and Marine-Derived Porous Scaffolds for Bone Tissue Engineering.

Bone is a vascularized and connective tissue. The cortical bone is the main part responsible for the support and protection of the remaining systems and organs of the body. The trabecular spongy bone serves as the storage of ions and bone marrow. As a dynamic tissue, bone is in a constant remodelling process to adapt to the mechanical demands and to repair small lesions that may occur. Nevertheless, due to the increased incidence of bone disorders, the need for bone grafts has been growing over the past decades and the development of an ideal bone graft with optimal properties remains a clinical challenge. This review addresses the bone properties (morphology, composition, and their repair and regeneration capacity) and puts the focus on the potential strategies for developing bone repair and regeneration materials. It describes the requirements for designing a suitable scaffold material, types of materials (polymers, ceramics, and composites), and techniques to obtain the porous structures (additive manufacturing techniques like robocasting or derived from marine skeletons) for bone tissue engineering applications. Overall, the main objective of this review is to gather the knowledge on the materials and methods used for the production of scaffolds for bone tissue engineering and to highlight the potential of natural porous structures such as marine skeletons as promising alternative bone graft substitute materials without any further mineralogical changes, or after partial or total transformation into calcium phosphate.

A randomized trial of nebulized 3% hypertonic saline with salbutamol in the treatment of acute bronchiolitis in hospitalized infants.

OBJECTIVE: Acute bronchiolitis is a common disorder of infants that often results in hospitalization. Apart from supportive care, no therapy has been shown to influence the course of the disease, except for a possible effect of nebulized hypertonic saline (HS). To determine whether this does have beneficial effects on length of stay in hospital or on severity scores, we undertook a double-blind, randomized, controlled trial in a pediatric department of a Portuguese hospital. METHODS: Previously healthy infants, younger than 12 months, hospitalized with mild-to-moderate acute viral bronchiolitis were randomized to receive either nebulized 3% (hypertonic, HS) or 0.9% (normal, NS) saline during their entire hospital stay. Primary endpoints were: length of hospital stay and severity scores on each day of hospitalization. Need for supplemental oxygen, further add-on medications and adverse effects were also analyzed. RESULTS: Sixty-eight patients completed the study (HS: 33; NS: 35). The median length of hospital stay did not differ between groups: HS: 5.6 ± 2.3 days; NS: 5.4 ± 2.1 days (P = 0.747). We found no difference between groups in severity scores from day 1 to day 4. There were no differences in need for supplemental oxygen or add-on medications. Patients in HS group had significantly more cough (46% vs. 20%, P = 0.025) and rhinorrhoe (58% vs. 31%, P = 0.30). CONCLUSION: This study does not support the use of nebulized HS over NS in therapy of hospitalized children with mild-to-moderate acute viral bronchiolitis.

[Pericarditis as a complication of meningococcal infection]. / Pericardite como complicação de doença meningocócica.

We describe a case of a three year old male who presents with meningococcal meningitis. The initial evolution was unremarkable but subsequently he developed pericarditis. The pericardial fluid had features of exudate but it was sterile. The response to antibiotics and anti-inflammatory medication was excellent.