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Objectives: This study aimed to improve the performance and mode of administration of a glass-reinforced hydroxyapatite synthetic bone substitute, Bonelike by Biosckin® (BL®), by association with a dextrin-based hydrogel, DEXGEL, to achieve an injectable and moldable device named DEXGEL Bone. Methods: Twelve participants requiring pre-molar tooth extraction and implant placement were enrolled in this study. BL® granules (250–500 µm) were administered to 6 randomized participants whereas the other 6 received DEXGEL Bone. After 6 months, a bone biopsy of the grafted area was collected for histological and histomorphometric evaluation, prior to implant placement. The performance of DEXGEL Bone and BL® treatments on alveolar preservation were further analyzed by computed tomography and Hounsfield density analysis. Primary implant stability was analyzed by implant stability coefficient technique. Results: The healing of defects was free of any local or systemic complications. Both treatments showed good osseointegration with no signs of adverse reaction. DEXGEL Bone exhibited increased granule resorption (p = 0.029) accompanied by a tendency for more new bone ingrowth (although not statistically significant) compared to the BL® group. The addition of DEXGEL to BL® granules did not compromise bone volume or density, being even beneficial for implant primary stability (p = 0.017). Conclusions: The hydrogel-reinforced biomaterial exhibited an easier handling, a better defect filling, and benefits in implant stability. Clinical relevance: This study validates DEXGEL Bone safety and performance as an injectable carrier of granular bone substitutes for alveolar ridge preservation. Trial registration: European Databank on Medical Devices (EUDAMED) No. CIV-PT-18–01-02,705; Registo Nacional de Estudos Clínicos, RNEC, No. 30122. [ABSTRACT FROM AUTHOR]

Notwithstanding the advances achieved in the last decades in the field of synthetic bone substitutes, the development of biodegradable 3D-printed scaffolds with ideal mechanical and biological properties remains an unattained challenge. In the present work, a new approach to produce synthetic bone grafts that mimic complex bone structure is explored. For the first time, three scaffolds of various composition, namely polycaprolactone (PCL), PCL/hydroxyapatite nanoparticles (HANp) and PCL/HANp/diacrylate poly(ethylene glycol) (PEGDA), were manufactured by extrusion. Following the production and characterisation of the scaffolds, an in vitro evaluation was carried out using human dental pulp stem/stromal cells (hDPSCs). Through the findings, it was possible to conclude that, in all groups, the scaffolds were successfully produced presenting networks of interconnected channels, adequate porosity for migration and proliferation of osteoblasts (approximately 50%). Furthermore, according to the in vitro analysis, all groups were considered non-cytotoxic in contact with the cells. Nevertheless, the group with PEGDA revealed hydrophilic properties (15.15° ± 4.06) and adequate mechanical performance (10.41 MPa ± 0.934) and demonstrated significantly higher cell viability than the other groups analysed. The scaffolds with PEGDA suggested an increase in cell adhesion and proliferation, thus are more appropriate for bone regeneration. To conclude, findings in this study demonstrated that PCL, HANp and PEGDA scaffolds may have promising effects on bone regeneration and might open new insights for 3D tissue substitutes. [ABSTRACT FROM AUTHOR]

Medical devices (MDs) are important health instruments, encompassing an enormous diversity of products, from simple ligatures to pacemakers, bone grafts or auxiliary life support machines. Despite the growing social and economic relevance of the MD industry in the health sector, its environmental problems have only recently started to be discussed. MDs companies worldwide are being pressed to assess the environmental impacts of their products by considering the full life cycle. These pressures are leading to the use of tools which promote fact-based environmental decision-making toward a more sustainable health sector. Life cycle assessment (LCA) and eco-design are well-known methods which may provide the MDs industrial sector with knowledge of the environmental impacts associated with their products and subsequently promote informed decisions leading to more sustainable materials, devices and services. This paper selects and reviews relevant studies using the methodology of LCA or eco-design, either applied in a singular basis or simulated, to access impacts of MDs. Seeking for a comparative analysis, this review is extended to LCA studies for the most used material in the MDs industry: the polymers. Results show that the number of studies is not vast, realizing the yet scarce use of either LCA and eco-design in the scientific literature for MDs. Nevertheless, it is observed that when applied either LCA and eco-deign can promote grounds for an increase in the environmental sustainability of MDs. [ABSTRACT FROM AUTHOR]

The development of injectable bone substitutes (IBS) have obtained great importance in the bone regeneration field, as a strategy to reach hardly accessible defects using minimally invasive techniques and able to fit to irregular topographies. In this scenario, the association of injectable hydrogels and bone graft granules is emerging as a well-established trend. Particularly, in situ forming hydrogels have arisen as a new IBS generation. An in situ forming and injectable dextrin-based hydrogel (HG) was developed, aiming to act as a carrier of granular bone substitutes and bioactive agents. In this work, the HG was associated to a granular bone substitute (Bonelike®) and implanted in goat critical-sized calvarial defects (14 mm) for 3, 6 and 12 weeks. The results showed that HG improved the handling properties of the Bonelike® granules and did not affect its osteoconductive features, neither impairing the bone regeneration process. Human multipotent mesenchymal stromal cells from the umbilical cord, extracellular matrix hydrolysates and the pro-angiogenic peptide LLKKK18 were also combined with the IBS. These bioactive agents did not enhance the new bone formation significantly under the conditions tested, according to micro-computed tomography and histological analysis. [ABSTRACT FROM AUTHOR]

The therapeutic effect of three polyvinyl alcohol (PVA) membranes loaded with electrically conductive materials - carbon nanotubes ( PVA-CNTs) and polypyrrole ( PVA-PPy) - were tested in vivo for neuro-muscular regeneration after an axonotmesis injury in the rat sciatic nerve. The membranes electrical conductivity measured was 1.5 ± 0.5 × 10−6 S/m, 579 ± 0.6 × 10−6 S/m, and 1837.5 ± 0.7 × 10−6 S/m, respectively. At week-12, a residual motor and nociceptive deficit were present in all treated groups, but at week-12, a better recovery to normal gait pattern of the PVA-CNTs and PVA-PPy treated groups was observed. Morphometrical analysis demonstrated that PVA-CNTs group presented higher myelin thickness and lower g-ratio. The tibialis anterior muscle, in the PVA-PPy and PVA-CNTs groups showed a 9% and 19% increase of average fiber size area and a 5% and 10% increase of the 'minimal Feret's diameter,' respectively. No inflammation, degeneration, fibrosis or necrosis were detected in lung, liver, kidneys, spleen, and regional lymph nodes and absence of carbon deposits was confirmed with Von Kossa and Masson-Fontana stains. In conclusion, the membranes of PVA-CNTs and PVA-PPy are biocompatible and have electrical conductivity. The higher electrical conductivity measured in PVA-CNTs membrane might be responsible for the positive results on maturation of myelinated fibers. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 1267-1280, 2017. [ABSTRACT FROM AUTHOR]

Polyvinyl alcohol hydrogel (PVA) is a water-soluble synthetic polymer that is commonly used in biomedical applications including vascular grafting. It was argued that the copolymerization of PVA with dextran (Dx) can result in improvement of blood-biomaterial interactions. The focus of this experimental study was to assess that interaction through an in vivo and in vitro evaluation of the coagulation system activation. The thrombogenicity of the copolymer was determined by quantification of platelet adhesion through the lactate dehydrogenase assay, determination of whole blood clotting time, and by quantification of platelet activation by flow cytometry. The thrombin-antithrombin complex blood levels were also determined. The obtained results for the in vitro assays suggested a non-thrombogenic profile for PVA/Dx. Additionally in vivo coagulation and hematological parameters were determined in an animal model after PVA/Dx vascular graft implantation. For coagulation homeostasis assessment, the intrinsic and extrinsic pathway's activation was determined by measuring prothrombin time (PT) and activated partial thromboplastin time (aPTT). Other markers of coagulation and inflammation activation including d-dimers, interleukin-6, and C-reactive protein were also assessed. The PVA/Dx copolymer tended to inhibit platelet adhesion/activation process and the contact activation process for coagulation. These results were also confirmed with the in vivo experiments where the measurements for APTT, interleukin-6, and C-reactive protein parameters were normal considering the species normal range of values. The response to those events is an indicator of the in vitro and in vivo hemocompatibility of PVA/Dx and it allows us to select this biomaterial for further preclinical trials in vascular reconstruction. © 2014 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 103A: 1366-1379, 2015. [ABSTRACT FROM AUTHOR]

Polyvinyl alcohol hydrogel (PVA) is a synthetic polymer with an increasing application in the biomedical field that can potentially be used for vascular grafting. However, the tissue and blood-material interactions of such gels and membranes are unknown in detail. The objectives of this study were to: (a) assess the biocompatibility and (b) hemocompatibility of PVA-based membranes in order to get some insight into its potential use as a vascular graft. PVA was evaluated isolated or in copolymerization with dextran (DX), a biopolymer with known effects in blood coagulation homeostasis. The effects of the mesenchymal stem cells (MSCs) isolated from the umbilical cord Wharton's jelly in the improvement of PVA biocompatibility and in the vascular regeneration were also assessed. The biocompatibility of PVA was evaluated by the implantation of membranes in subcutaneous tissue using an animal model (sheep). Histological samples were assessed and the biological response parameters such as polymorphonuclear neutrophilic leucocytes and macrophage scoring evaluated in the implant/tissue interface by International Standards Office (ISO) Standard 10993-6 (annex E). According to the scoring system based on those parameters, a total value was obtained for each animal and for each experimental group. The in vitro hemocompatibility studies included the classic hemolysis assay and both human and sheep bloods were used. Relatively to biocompatibility results, PVA was slightly irritant to the surrounding tissues; PVA-DX or PVA plus MSCs groups presented the lowest score according to ISO Standard 10993-6. Also, PVA was considered a nonhemolytic biomaterial, presenting the lowest values for hemolysis when associated to DX. © 2014 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 102A: 4262-4275, 2014. [ABSTRACT FROM AUTHOR]

Human mesenchymal stem cells (hMSCs) from umbilical cord (UC) blood (UCB) and matrix are tested clinically for a variety of pathologies but in vitro expansion using culture media containing fetal bovine serum (FBS) is essential to achieve appropriate cell numbers for clinical use. Human UCB plasma (hUCBP) can be used as a supplement for hMSCs culture, since UCB is rich in soluble growth factors and due to worldwide increased number of cryopreserved UCB units in public and private banks, without the disadvantages listed for FBS. On the other hand, the culture media enriched in growth factors produced by these hMSCs in expansion (Conditioned medium - CM) can be an alternative to hMSCs application. The CM of the hMSCs from the UC might be a better therapeutic option compared to cell transplantation, as it can benefit from the local tissue response to the secreted molecules without the difficulties and complications associated to the engraftment of the allo- or xeno-transplanted cells. These facts drove us to know the detailed composition of the hUCBP and CM, by 1H-NMR and Multiplexing LASER Bead Technology. hUCBP is an adequate alternative for the FBS and the CM and hUCBP are important sources of growth factors, which can be used in MSCs-based therapies. Some of the major proliferative, chemotactic and immunomodulatory soluble factors (TGF-β, G-CSF, GM-CSF, MCP-1, IL-6, IL-8) were detected in high concentrations in CM and even higher in hUCBP. The results from 1H-NMR spectroscopic analysis of CM endorsed a better understanding of hMSCs metabolism during in vitro culture, and the relative composition of several metabolites present in CM and hUCBP was obtained. The data reinforces the potential use of hUCBP and CM in tissue regeneration and focus the possible use of hUCBP as a substitute for the FBS used in hMSCs in vitro culture. [ABSTRACT FROM AUTHOR]

A novel bioactive bone substitute with improved osteoblastic performance and effective antibacterial activity was developed, using a completely new approach based on samarium (Sm [sup 3+]) doped P[sub 2]O[sub 5] glassreinforced hydroxyapatite composites (GR-HA). The composites were prepared by adding 2.5% (w/w) of the P[sub 2]O[sub 5] glass to 97.5% (w/w) of HA. Four composites were developed, i.e. one non-doped composite, and three Sm[sup 3+] doped composites prepared with the P[sub 2]O[sub 5] glass containing 0.5, 1 and 2 (mol%) of Sm[sub 2]O[sub 3]. The composites were labeled as GR-HA_control, GR-HA_0.5Sm, GR-HA_1Sm and GR-HA_2Sm. The composites were physicochemical and mechanically characterized, namely performing SEM, EDS and XRD analysis and flexural bending strength (FBS) assessment. The incorporation of Sm[sup 3+] in the GRHA matrix resulted in the presence of a residual Sm[sup 3+] containing phase besides HA, b-TCP and a-TCP phases, increased surface hydrophilicity and slightly higher FBS. Sm[sup 3+] doped composites exhibited improved osteoblastic cell response, as evidenced by a better F-actin cytoskeleton organization and higher cell proliferation and expression of relevant osteoblastic genes. In addition, adhesion of Staphylococcus aureus and Staphylococcus epidermidis was greatly reduced on these composites. The improved osteoblastic behavior and the antibacterial effects were dependent on the amount of Samarium in the composite, this being particularly evident in the composite with a higher Sm3+ content. Therefore, the developed composite GR-HA_2Sm appears as a successful bone substitute with osteoconductive and antibacterial properties. [ABSTRACT FROM AUTHOR]