RESUMO
A face shield is a secondary personal protective equipment (PPE) for healthcare workers (HCW). Worn with the appropriate face masks/respirators, it provides short term barrier protection against potentially infectious droplet particles. Coronavirus disease 2019 (COVID-19) caused a spike in demand for PPE, leading to a shortage and risking the safety of HCW. Transport restrictions further challenged the existing PPE supply chain which has been reliant on overseas-based manufacturers. Despite the urgency in demand, PPE must be properly tested for functionality and quality. We describe the establishment of local face shields manufacture in Western Australia to ensure adequate PPE for HCW. Ten thousand face shields for general use (standard) and for ear, nose and throat (ENT) specialist use were produced. Materials and design considerations are described, and the face shields were vigorously tested to the relevant Standards to ensure their effectiveness as a protective barrier, including splash and impact resistance. Comparative testing with traditional and other novel face shields was also undertaken. Therapeutic Goods Administration (TGA) licence was obtained to manufacture and supply the face shields as a Class I medical device. The swiftness of process is a credit to collaboration from industry, academia and healthcare.
RESUMO
Tuneable, bioactive hydrogels present an attractive option as cell-instructive substrates for tissue regeneration. Properties mimicking the extracellular matrix at the site of injury are sought after, in particular the ability to regulate growth factors that are key to the regeneration process. This study demonstrates the successful formation of hydrogels with heparin functionalities and fibroblast growth factor-2 (FGF-2). Poly(2-hydroxyethyl methacrylate)-heparin hydrogels were capable of retaining FGF-2 by specific binding to heparin and subsequently showed sustained presentation of the growth factor to mesenchymal stromal cells (MSC). Heparin acted as stable anchoring molecules for FGF-2 on the substrate and the synergistic effect of the ensuing heparin-FGF-2 complex was evident in supporting long term cell growth. The presence of heparin during 3D scaffold formation was also found to introduce surface roughness and microporosity to the resulting hydrogels. While FGF-2 has been known to encourage MSC growth and maintain their multilineage potential, other heparin-binding ligands such as bone morphogenetic proteins are potent differentiation stimuli for MSC. Therefore preserving MSC multipotency or a push toward a differentiation pathway may be pursued by the choice of ligand applied to and bound by the heparin functionalities on the current substrate.
Assuntos
Preparações de Ação Retardada/química , Fator 2 de Crescimento de Fibroblastos/administração & dosagem , Heparina/química , Hidrogéis/química , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Fator 2 de Crescimento de Fibroblastos/farmacologia , Humanos , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/efeitos dos fármacosRESUMO
Cranioplasty is necessary for patients that have undergone craniectomy following trauma, stroke or other causes of elevated intracranial pressure. This study assessed the effectiveness of treating cranial defects with allogeneic mesenchymal stromal cells (MSC) on a ceramic carrier and polymer scaffold, to produce viable bone and healing of a cranial void. Patients underwent a baseline computed tomography (CT) scan for construct design. Two sets of interlocking moulds were three-dimensional printed to enable shaping of two polymer meshes, which formed the boundaries of the construct corresponding to restoration of the skull interna and externa. In vitro expanded donor MSC were seeded onto ceramic granules in a good manufacturing practices facility. The inner mesh was placed in theatre, followed by the cell-loaded granules, and the outer mesh. Patients were followed-up at 3, 6 and 12 months and cosmesis assessed visually, while bone formation was assessed by CT scans at 1 day, 3 months and 12 months. Manufacture of the construct and surgery was uneventful for all three patients. Initial cosmesis was excellent with no complications. New bone formation was demonstrated by analysis of CT data; however, bone resorption was noted in all 3 cases on the 12-month CT scan. The lack of rigidity of the construct in an environment with continuous pulsatile movement may be preventing the formation of solid bone. It is possible to produce a customized allogeneic MSC construct for cranial reconstruction to replace cranial bone with good cosmesis, using a combination of medical computer modelling, rapid-prototyping and tissue engineering.
Assuntos
Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais/citologia , Crânio/fisiologia , Adolescente , Adulto , Idoso , Densidade Óssea , Feminino , Humanos , Implantes Experimentais , Masculino , Pessoa de Meia-Idade , Engenharia Tecidual , Tomografia Computadorizada por Raios X , Transplante Homólogo , Adulto JovemRESUMO
BACKGROUND: Poly Implant Prothèse implants were recalled in Australia in April of 2010 following concerns of higher than expected rupture rates and the use of unauthorized industrial grade silicone as a filler material. Although subsequent investigations found that the gel filler material does not pose a threat to human health, the important question of what caused a relatively modern breast implant to have such a poor outcome compared with contemporary silicone breast implants is yet to be addressed. METHODS: From a cohort of 27 patients, 19 ruptured Poly Implant Prothèse breast implants were subjected to a range of mechanical tests and microscopic/macroscopic investigations to evaluate possible changes in properties as a result of implantation. New Poly Implant Prothèse implants were used as controls. RESULTS: All samples, explanted and controls, complied with the requirements for shell integrity as specified in the International Organization for Standardization 14607. Compression testing revealed rupture rates similar to those reported in the literature. Shell thickness was highly variable, with most shells having regions below the minimum thickness of 0.57 mm that was specified by the manufacturer. Potential regions of stress concentration were observed on the smooth inner surfaces and outer textured surfaces. CONCLUSIONS: The high incidence of Poly Implant Prothèse shell rupture is most likely a result of inadequate quality control, with contributory factors being shell thickness variation and manufacturing defects on both inner and outer surfaces of the shell. No evidence of shell degradation with implantation time was determined.
Assuntos
Implantes de Mama , Falha de Prótese , Géis de Silicone , Remoção de Dispositivo , Feminino , Humanos , Teste de Materiais/métodos , Desenho de PróteseRESUMO
The extracellular matrix is continually remodelled by the action of various enzymes such as heparanase, which specifically targets heparan sulfate (HS) and is found in human platelets at high levels. The activity of heparin-containing hydrogels following incubation with platelet extract (PE) was investigated in order to simulate the responses that might occur when the hydrogels, as tissue engineered scaffolds, come in contact with blood products at the site of an injury. The heparanase activity of PE on heparin, used as a model of HS, was confirmed by the decrease in molecular weight. PE treatment diminished heparin's anticoagulation property but increased its FGF-2 signalling activity, suggesting that the PE's heparanase activity cleaves at the 3-O-sulfated glucosamine to produce large fragments that can signal cell receptors. The dual effect observed when poly(vinyl alcohol)/heparin co-hydrogels were incubated with PE supports the hypothesis of platelets having the capacity to limit anticoagulation and thus promote blood clot formation, which may be critical in the process of tissue repair.
Assuntos
Sobrevivência Celular/efeitos dos fármacos , Glucuronidase/química , Heparina/química , Heparina/farmacologia , Hidrogéis/química , Hidrogéis/farmacologia , Linhagem Celular , Humanos , Teste de MateriaisRESUMO
The potent oxidants hypochlorous acid (HOCl) and hypobromous acid (HOBr) are produced extracellularly by myeloperoxidase, following release of this enzyme from activated leukocytes. The subendothelial extracellular matrix is a key site for deposition of myeloperoxidase and damage by myeloperoxidase-derived oxidants, with this damage implicated in the impairment of vascular cell function during acute inflammatory responses and chronic inflammatory diseases such as atherosclerosis. The heparan sulfate proteoglycan perlecan, a key component of the subendothelial extracellular matrix, regulates important cellular processes and is a potential target for HOCl and HOBr. It is shown here that perlecan binds myeloperoxidase via its heparan sulfate side chains and that this enhances oxidative damage by myeloperoxidase-derived HOCl and HOBr. This damage involved selective degradation of the perlecan protein core without detectable alteration of its heparan sulfate side chains, despite the presence of reactive GlcNH(2) residing within this glycosaminoglycan. Modification of the protein core by HOCl and HOBr (measured by loss of immunological recognition of native protein epitopes and the appearance of oxidatively-modified protein epitopes) was associated with an impairment of its ability to support endothelial cell adhesion, with this observed at a pathologically-achievable oxidant dose of 425nmol oxidant/mg protein. In contrast, the heparan sulfate chains of HOCl/HOBr-modified perlecan retained their ability to bind FGF-2 and collagen V and were able to promote FGF-2-dependent cellular proliferation. Collectively, these data highlight the potential role of perlecan oxidation, and consequent deregulation of cell function, in vascular injuries by myeloperoxidase-derived HOCl and HOBr.
Assuntos
Bromatos/metabolismo , Proteoglicanas de Heparan Sulfato/metabolismo , Ácido Hipocloroso/metabolismo , Oxidantes/metabolismo , Peroxidase/metabolismo , Animais , Adesão Celular/fisiologia , Células Cultivadas , Colágeno Tipo V/metabolismo , Células Endoteliais/citologia , Células Endoteliais/metabolismo , Epitopos/química , Fator 2 de Crescimento de Fibroblastos/metabolismo , Glicosaminoglicanos/metabolismo , Proteoglicanas de Heparan Sulfato/química , Humanos , Oxirredução , Ligação ProteicaRESUMO
Synthetic scaffolds show great promise for use in tissue engineering due to their ability to mimic some aspects of the extracellular matrix, however, their use has been hindered by the lack of inherent recognition sites that are required for protein and cell interactions. Heparan sulfate (HS), a glycosaminoglycan polysaccharide present in the basement membrane and on the cell surface, binds growth factors and cytokines and enhances the signalling of these ligands by forming complexes with their receptors. This study focuses on the formation of photopolymerised hydrogels derived from methacrylated macromers of poly(vinyl alcohol) (PVA) and heparin, with the aim of imparting the growth factor activation property of heparin to the synthetic scaffolds. It was shown that the methacrylate group attachment on heparin did not result in the fragmentation of heparin molecules, and that the biological activity of the methacrylated heparin was preserved as determined by tests on its anticoagulation properties and ability to signal fibroblast growth factor-2 (FGF-2). The addition of heparin into the PVA hydrogels resulted in an increase in mass swelling ratio from 5.8 for pure PVA to 6.5 and 6.6 for PVA/heparin co-hydrogels of 19/1 and 17.5/2.5 (w/w) compositions, respectively. It is believed that heparin molecules can be added into a synthetic PVA scaffold without adversely affecting the structural and mechanical stability of the PVA scaffold. The tensile moduli of the co-hydrogels remained close to that of PVA hydrogels (61 kPa), even up to 2.5% heparin composition (PVA/hep 17.5/2.5). Finally, the co-hydrogels were found to retain the growth factor signalling activity of heparin at equilibrium.