A systematic review of literature on occupational health and safety interventions for older workers.

As the global population ages there is an imperative to enhance labour participation of older workers in ways that support good physical and psychological health. However, there is limited guidance for organisations on how to do this effectively. This systematic review examined literature identified through four databases and a targeted web-search, yielding 39 PRISMA records (32 scholarly, seven grey literature) reporting workplace interventions aimed at improving the injury outcomes of older workers. The review revealed that organisational and composite interventions may be most effective, although an absence of robust research in this area and a scarcity of empirical evidence-based interventions known to improve injury outcomes for older workers was noted. Responding to these shortcomings, this article presents 'A future research agenda for older worker health, safety and well-being interventions.' This systems-based approach has a dual focus on organisational and composite interventions combined with robust research design.Practitioner summary: We conducted a systematic literature review of studies focussed on workplace interventions to improve the physical and psychological safety of older workers. Within the existing literature, evidence for effective interventions and guidance for organisations is weak. We present a future research agenda with a systems approach to address these gaps.

Corrected and Republished from: "A Novel, Multiple-Antigen Pneumococcal Vaccine Protects against Lethal Streptococcus pneumoniae Challenge".

Current vaccination against Streptococcus pneumoniae uses vaccines based on capsular polysaccharides from selected serotypes and has led to nonvaccine serotype replacement disease. We have investigated an alternative serotype-independent approach, using multiple-antigen vaccines (MAV) prepared from S. pneumoniae TIGR4 lysates enriched for surface proteins by a chromatography step after culture under conditions that induce expression of heat shock proteins (Hsp; thought to be immune adjuvants). Proteomics and immunoblot analyses demonstrated that, compared to standard bacterial lysates, MAV was enriched with Hsps and contained several recognized protective protein antigens, including pneumococcal surface protein A (PspA) and pneumolysin (Ply). Vaccination of rodents with MAV induced robust antibody responses to multiple serotypes, including nonpneumococcal conjugate vaccine serotypes. Homologous and heterologous strains of S. pneumoniae were opsonized after incubation in sera from vaccinated rodents. In mouse models, active vaccination with MAV significantly protected against pneumonia, while passive transfer of rabbit serum from MAV-vaccinated rabbits significantly protected against sepsis caused by both homologous and heterologous S. pneumoniae strains. Direct comparison of MAV preparations made with or without the heat shock step showed no clear differences in protein antigen content and antigenicity, suggesting that the chromatography step rather than Hsp induction improved MAV antigenicity. Overall, these data suggest that the MAV approach may provide serotype-independent protection against S. pneumoniae.

Production of a high purity, C-tagged hepatitis B surface antigen fusion protein VLP vaccine for malaria expressed in Pichia pastoris under cGMP conditions.

Virus-like particles (VLPs) induce strong humoral and cellular responses and have formed the basis of some currently licensed vaccines. Here, we present the method used for the production of R21, a VLP-based anti-sporozoite malaria vaccine, under current Clinical Good Manufacturing Practice regulations (cGMP). Previous preclinical studies in BALB/c mice showed that R21 produced almost complete protection against sporozoite challenge with transgenic Plasmodium berghei parasites. Here, we have modified the preclinical production process to enable the production of sufficient quantities of highly pure, clinical-grade material for use in human clinical trials. The R21 construct was re-engineered to include a C-tag to allow affinity-based separation from the major contaminant alcohol oxidase 1 (AOX 1, ~74 kDa). To our knowledge, this is the first use of C-tag technology to purify a VLP vaccine candidate for use in human clinical trials. The R21 vaccine has shown high-level efficacy in an African Phase IIb trial, and multiple clinical trials are underway to assess the safety and efficacy of the vaccine. Our findings support the future use of C-tag platform technologies to enable cGMP-compliant biomanufacturing of high purity yeast-expressed VLP-based vaccines for early phase clinical trials when clinical grade material is required in smaller quantities in a quick time frame.

State of science: the future of work - ergonomics and human factors contributions to the field.

This article is concerned with scholarly ergonomics and human factors (E/HF) contributions to date to the field of research inquiry known as the 'future of work'. The review considers E/HF perspectives on how the nature of work is changing and what this means for the practice of E/HF and for human performance and wellbeing at work. This field of research has attracted much attention from scholars from various disciplines as flexible working arrangements and casualised employment, in particular, have come under the microscope during the COVID-19 pandemic. The article begins by setting out the future of work field, focussing on the mega trends and future of work forces that are most relevant to the discipline. Next, E/HF contributions to this field are identified and discussed. Surprisingly, given the E/HF tradition as a system discipline fundamentally concerned with the study of human work, and as a contributor to transdisciplinary research related to the design of work systems, a search of the scholarly literature found few contributions outside of the automation systems field that addressed the future of work and E/HF directly. A research agenda is presented to address gaps in current knowledge in a number of key future of work domains. Practitioner's Summary: We reflect on E/HF contributions to the 'future of work' field and how the practice of E/HF needs to consider the changing nature of work. We outline future of work concerns and suggest research areas for further E/HF attention towards the design of decent and sustainable work for all. Abbreviations: E/HF: ergonomics and human factors; ILO: International Labour Organisation; COVID-19.

Characterizing Cross-Linking Within Polymeric Biomaterials in the SEM by Secondary Electron Hyperspectral Imaging.

A novel capability built upon secondary electron (SE) spectroscopy provides an enhanced cross-linking characterization toolset for polymeric biomaterials, with cross-linking density and variation captured at a multiscale level. The potential of SE spectroscopy for material characterization has been investigated since 1947. The absence of suitable instrumentation and signal processing proved insurmountable barriers to applying SE spectroscopy to biomaterials, and consequently, capturing SE spectra containing cross-linking information is a new concept. To date, cross-linking extent is inferred from analytical techniques such as nuclear magnetic resonance (NMR), differential scanning calorimetry, and Raman spectroscopy (RS). NMR provides extremely localized information on the atomic scale and molecular scale, while RS information volume is on the microscale. Other methods for the indirect study of cross-linking are bulk mechanical averaging methods, such as tensile and compression modulus testing. However, these established averaging methods for the estimation of polymer cross-linking density are incomplete because they fail to provide information of spatial distributions within the biomaterial morphology across all relevant length scales. The efficacy of the SE spectroscopy capability is demonstrated in this paper by the analysis of poly(glycerol sebacate)-methacrylate (PGS-M) at different degrees of methacrylation delivering new insights into PGS-M morphology.

A Novel, Multiple-Antigen Pneumococcal Vaccine Protects against Lethal Streptococcus pneumoniae Challenge.

Current vaccination against Streptococcus pneumoniae uses vaccines based on capsular polysaccharides from selected serotypes and has led to nonvaccine serotype replacement disease. We have investigated an alternative serotype-independent approach, using multiple-antigen vaccines (MAV) prepared from S. pneumoniae TIGR4 lysates enriched for surface proteins by a chromatography step after culture under conditions that induce expression of heat shock proteins (Hsp; thought to be immune adjuvants). Proteomics and immunoblot analyses demonstrated that, compared to standard bacterial lysates, MAV was enriched with Hsps and contained several recognized protective protein antigens, including pneumococcal surface protein A (PspA) and pneumolysin (Ply). Vaccination of rodents with MAV induced robust antibody responses to multiple serotypes, including nonpneumococcal conjugate vaccine serotypes. Homologous and heterologous strains of S. pneumoniae were opsonized after incubation in sera from vaccinated rodents. In mouse models, active vaccination with MAV significantly protected against pneumonia, while passive transfer of rabbit serum from MAV-vaccinated rabbits significantly protected against sepsis caused by both homologous and heterologous S. pneumoniae strains. Direct comparison of MAV preparations made with or without the heat shock step showed no clear differences in protein antigen content and antigenicity, suggesting that the chromatography step rather than Hsp induction improved MAV antigenicity. Overall, these data suggest that the MAV approach may provide serotype-independent protection against S. pneumoniae.

Adenovirus 5 recovery using nanofiber ion-exchange adsorbents.

Viral vectors such as adenovirus have successful applications in vaccines and gene therapy but the manufacture of the high-quality virus remains a challenge. It is desirable to use the adsorption-based chromatographic separations that so effectively underpin the therapeutic protein manufacture. However fundamental differences in the size and stability of this class of product mean it is necessary to revisit the design of sorbent's morphology and surface chemistry. In this study, the behaviour of a cellulose nanofiber ion-exchange sorbent derivatised with quaternary amine ligands at defined densities is characterised to address this. This material was selected as it has a large accessible surface area for viral particles and rapid process times. Initially, the impact of surface chemistry on infective product recovery using low (440 µmol/g), medium (750 µmol/g), and high (1029 µmol/g) ligand densities is studied. At higher densities product stability is reduced, this effect increased with prolonged adsorption durations of 24 min with just ~10% loss at low ligand density versus ~50% at high. This could be mitigated by using a high flow rate to reduce the cycle time to ~1 min. Next, the impact of ligand density on the separation's resolution was evaluated. Key to understanding virus quality is the virus particle: infectious virus particle ratio. It was found this parameter could be manipulated using ligand density and elution strategy. Together this provides a basis for viral vector separations that allows for their typically low titres and labile nature by using high liquid velocity to minimise both load and on-column times while separating key product and process-related impurities.

Second Harmonic Generation microscopy reveals collagen fibres are more organised in the cervix of postmenopausal women.

BACKGROUND: During labour, the cervix undergoes a series of changes to allow the passage of the fetoplacental unit. While this visible transformation is well-described, the underlying and causative microscopic changes, in which collagen plays a major role, are poorly understood and difficult to visualise. Recent studies in mice and humans have shown that Second Harmonic Generation (SHG) microscopy, a non-destructive imaging technique, can detect changes in the cervical collagen. However, the question of whether SHG can identify changes in the arrangement of cervical collagen at different physiological stages still needs addressing. Therefore, this study aimed to compare the cervical collagen alignment between pre- and postmenopausal women using SHG and to generate proof-of-concept data prior to assessing this technique in pregnancy. METHODS: Cervical biopsies from premenopausal (n = 4) and postmenopausal (n = 4) multiparous women undergoing hysterectomy for benign conditions were cross-sectionally scanned using an upright confocal microscope. SHG images were collected in Z-stacks and qualitatively evaluated using semi-quantitative scoring (0-3 in ascending degree of alignment) by assessors who were unaware of the classification of the SHG images, and quantitatively, using 2D Fourier transformation analysis. The dominant orientation and difference in dispersion of collagen fibres in each z-stack (X ± SD) was calculated and compared between groups. RESULTS: Qualitatively, collagen fibres appeared more organised in postmenopausal women, [premenopausal: median 0, range (0-1), postmenopausal: median 1.25, range (1-3); X 2 (df = 5) = 19.35, p = 0.002]. Quantitatively, there was a statistically significant difference in collagen fibre dispersion between premenopausal (5.39° ± 12.68°) and postmenopausal women (-1.58° ± 8.24°), [Welch's t-test (245.54) = 5.54, p < 0.01], with no significant differences in dispersion within each group [premenopausal, Welch's F (7, 57.23) = 1.84, p = 0.098; postmenopausal, Welch's F (7, 57.28) = 1.39, p = 0.23]. CONCLUSION: These results suggest an increased alignment of cervical collagen in postmenopausal women which may result in increased stiffness and reduced compliance, confirm that SHG microscopy can provide qualitative and quantitative information about cervical collagen orientation without sample preparation, and support further research to explore SHG as a means of assessing cervical remodelling to predict the timing of term and preterm labour.

Antibody Response is More Likely to Pneumococcal Proteins Than to Polysaccharide After HIV-associated Invasive Pneumococcal Disease.

BACKGROUND: Human immunodeficiency virus (HIV)-infected individuals are at increased risk of invasive pneumococcal disease (IPD). In order to assess the immunogenicity of pneumococcal proteins and polysaccharide, we investigated protein and serotype-specific antibody responses after HIV-associated IPD. METHODS: Specific antipneumococcal immunoglobulin G to 27 pneumococcal protein antigens and 30 serotype polysaccharides was measured in plasma before and after IPD in HIV-infected individuals and compared to HIV-infected individuals without IPD. RESULTS: Over time, 81% of IPD cases responded to at least 1 protein compared to 51% of non-IPD controls. HIV IPD cases responded to more proteins than non-IPD controls (8.6 ± 8.4 vs 4.2 ± 7.6 proteins; P = .01), and had a significantly higher probability of yielding an antibody response to the proteins PiaA, PsaA, and PcpA. Twenty-two percent of HIV-infected individuals with IPD had a serotype-specific antibody response. Younger age at the time of IPD was the only predictor of a serotype-specific pneumococcal antibody response, whereas we did not identify predictors of a protein-specific antibody response. CONCLUSIONS: Antibody responses occurred more frequently to pneumococcal proteins than to polysaccharide, and protein antibodies persisted for longer than polysaccharide-specific antibodies. PcpA, PiaA, and PsaA were the most immunogenic proteins.

DNA damage response at telomeres contributes to lung aging and chronic obstructive pulmonary disease.

Cellular senescence has been associated with the structural and functional decline observed during physiological lung aging and in chronic obstructive pulmonary disease (COPD). Airway epithelial cells are the first line of defense in the lungs and are important to COPD pathogenesis. However, the mechanisms underlying airway epithelial cell senescence, and particularly the role of telomere dysfunction in this process, are poorly understood. We aimed to investigate telomere dysfunction in airway epithelial cells from patients with COPD, in the aging murine lung and following cigarette smoke exposure. We evaluated colocalization of γ-histone protein 2A.X and telomeres and telomere length in small airway epithelial cells from patients with COPD, during murine lung aging, and following cigarette smoke exposure in vivo and in vitro. We found that telomere-associated DNA damage foci increase in small airway epithelial cells from patients with COPD, without significant telomere shortening detected. With age, telomere-associated foci increase in small airway epithelial cells of the murine lung, which is accelerated by cigarette smoke exposure. Moreover, telomere-associated foci predict age-dependent emphysema, and late-generation Terc null mice, which harbor dysfunctional telomeres, show early-onset emphysema. We found that cigarette smoke accelerates telomere dysfunction via reactive oxygen species in vitro and may be associated with ataxia telangiectasia mutated-dependent secretion of inflammatory cytokines interleukin-6 and -8. We propose that telomeres are highly sensitive to cigarette smoke-induced damage, and telomere dysfunction may underlie decline of lung function observed during aging and in COPD.

Pulsatile exposure to simulated reflux leads to changes in gene expression in a 3D model of oesophageal mucosa.

Oesophageal exposure to duodenogastroesophageal refluxate is implicated in the development of Barrett's metaplasia (BM), with increased risk of progression to oesophageal adenocarcinoma. The literature proposes that reflux exposure activates NF-κB, driving the aberrant expression of intestine-specific caudal-related homeobox (CDX) genes. However, early events in the pathogenesis of BM from normal epithelium are poorly understood. To investigate this, our study subjected a 3D model of the normal human oesophageal mucosa to repeated, pulsatile exposure to specific bile components and examined changes in gene expression. Initial 2D experiments with a range of bile salts observed that taurochenodeoxycholate (TCDC) impacted upon NF-κB activation without causing cell death. Informed by this, the 3D oesophageal model was repeatedly exposed to TCDC in the presence and absence of acid, and the epithelial cells underwent gene expression profiling. We identified ~300 differentially expressed genes following each treatment, with a large and significant overlap between treatments. Enrichment analysis (Broad GSEA, DAVID and Metacore™; GeneGo Inc) identified multiple gene sets related to cell signalling, inflammation, proliferation, differentiation and cell adhesion. Specifically NF-κB activation, Wnt signalling, cell adhesion and targets for the transcription factors PTF1A and HNF4α were highlighted. Our data suggest that HNF4α isoform switching may be an early event in Barrett's pathogenesis. CDX1/2 targets were, however, not enriched, suggesting that although CDX1/2 activation reportedly plays a role in BM development, it may not be an initial event. Our findings highlight new areas for investigation in the earliest stages of BM pathogenesis of oesophageal diseases and new potential therapeutic targets.

Mechanistic differences between phenotypes of chronic lung allograft dysfunction after lung transplantation.

Distinct phenotypes of chronic lung allograft dysfunction (CLAD) after lung transplantation are emerging with lymphocytic bronchiolitis (LB)/azithromycin reversible allograft dysfunction (ARAD), classical or fibrotic bronchiolitis obliterans syndrome (BOS), and restrictive allograft syndrome (RAS) proposed as separate entities. We have additionally identified lung transplant recipients with prior LB, demonstrating persistent airway neutrophilia (PAN) despite azithromycin treatment. The aim of this study was to evaluate differences in the airway microenvironment in different phenotypes of CLAD. Bronchoalveolar lavage (BAL) from recipients identified as stable (control), LB/ARAD, PAN, BOS, and RAS were evaluated for differential cell counts and concentrations of IL-1α, IL-1ß, IL-6, IL-8, and TNF-α. Primary human bronchial epithelial cells were exposed to BAL supernatants from different phenotypes and their viability measured. BOS and RAS showed increased BAL neutrophilia but no change in cytokine concentrations compared with prediagnosis. In both LB/ARAD and PAN, significant increases in IL-1α, IL-1ß, and IL-8 were present. BAL IL-6 and TNF-α concentrations were increased in PAN and only this phenotype demonstrated decreased epithelial cell viability after exposure to BAL fluid. This study demonstrates clear differences in the airway microenvironment between different CLAD phenotypes. Systematic phenotyping of CLAD may help the development of more personalized approaches to treatment.

Controlled human infection and rechallenge with Streptococcus pneumoniae reveals the protective efficacy of carriage in healthy adults.

RATIONALE: The immunological and protective role of pneumococcal carriage in healthy adults is not known, but high rates of disease and death in the elderly are associated with low carriage prevalence. OBJECTIVES: We employed an experimental human pneumococcal carriage model to investigate the immunizing effect of a single carriage episode. METHODS: Seventy healthy adults were challenged, and of those with carriage, 10 were rechallenged intranasally with live 6B Streptococcus pneumoniae up to 11 months after clearance of the first carriage episode. Serum and nasal wash antibody responses were measured before and after each challenge. MEASUREMENTS AND MAIN RESULTS: A total of 29 subjects were experimentally colonized. No subjects were colonized by experimental rechallenge, demonstrating the protective effect of initial carriage against subsequent infection. Carriage increased both mucosal and serum IgG levels to pneumococcal proteins and polysaccharide, resulting in a fourfold increase in opsonophagocytic activity. Importantly, passive transfer of postcarriage sera from colonized subjects conferred 70% protection against lethal challenge by a heterologous strain in a murine model of invasive pneumococcal pneumonia. These levels were significantly higher than the protection conferred by either precarriage sera (30%) or saline (10%). CONCLUSIONS: Experimental human carriage resulted in mucosal and systemic immunological responses that conferred protection against recolonization and invasive pneumococcal disease. These data suggest that mucosal pneumococcal vaccination strategies may be important for vulnerable patient groups, particularly the elderly, who do not sustain carriage.

Dinuclear ruthenium(II) complexes as two-photon, time-resolved emission microscopy probes for cellular DNA.

The first transition-metal complex-based two-photon absorbing luminescence lifetime probes for cellular DNA are presented. This allows cell imaging of DNA free from endogenous fluorophores and potentially facilitates deep tissue imaging. In this initial study, ruthenium(II) luminophores are used as phosphorescent lifetime imaging microscopy (PLIM) probes for nuclear DNA in both live and fixed cells. The DNA-bound probes display characteristic emission lifetimes of more than 160 ns, while shorter-lived cytoplasmic emission is also observed. These timescales are orders of magnitude longer than conventional FLIM, leading to previously unattainable levels of sensitivity, and autofluorescence-free imaging.

The use of microphysiological systems to model metastatic cancer.

Cancer is one of the leading causes of death in the 21st century, with metastasis of cancer attributing to 90% of cancer-related deaths. Therefore, to improve patient outcomes there is a need for better preclinical models to increase the success of translating oncological therapies into the clinic. Current traditional staticin vitromodels lack a perfusable network which is critical to overcome the diffusional mass transfer limit to provide a mechanism for the exchange of essential nutrients and waste removal, and increase their physiological relevance. Furthermore, these models typically lack cellular heterogeneity and key components of the immune system and tumour microenvironment. This review explores rapidly developing strategies utilising perfusable microphysiological systems (MPS) for investigating cancer cell metastasis. In this review we initially outline the mechanisms of cancer metastasis, highlighting key steps and identifying the current gaps in our understanding of the metastatic cascade, exploring MPS focused on investigating the individual steps of the metastatic cascade before detailing the latest MPS which can investigate multiple components of the cascade. This review then focuses on the factors which can affect the performance of an MPS designed for cancer applications with a final discussion summarising the challenges and future directions for the use of MPS for cancer models.

Development of PCL PolyHIPE Substrates for 3D Breast Cancer Cell Culture.

Cancer is a becoming a huge social and economic burden on society, becoming one of the most significant barriers to life expectancy in the 21st century. In particular, breast cancer is one of the leading causes of death for women. One of the most significant difficulties to finding efficient therapies for specific cancers, such as breast cancer, is the efficiency and ease of drug development and testing. Tissue-engineered (TE) in vitro models are rapidly developing as an alternative to animal testing for pharmaceuticals. Additionally, porosity included within these structures overcomes the diffusional mass transfer limit whilst enabling cell infiltration and integration with surrounding tissue. Within this study, we investigated the use of high-molecular-weight polycaprolactone methacrylate (PCL-M) polymerised high-internal-phase emulsions (polyHIPEs) as a scaffold to support 3D breast cancer (MDA-MB-231) cell culture. We assessed the porosity, interconnectivity, and morphology of the polyHIPEs when varying mixing speed during formation of the emulsion, successfully demonstrating the tunability of these polyHIPEs. An ex ovo chick chorioallantoic membrane assay identified the scaffolds as bioinert, with biocompatible properties within a vascularised tissue. Furthermore, in vitro assessment of cell attachment and proliferation showed promising potential for the use of PCL polyHIPEs to support cell growth. Our results demonstrate that PCL polyHIPEs are a promising material to support cancer cell growth with tuneable porosity and interconnectivity for the fabrication of perfusable 3D cancer models.

Surfactant-free gelatin-stabilised biodegradable polymerised high internal phase emulsions with macroporous structures.

High internal phase emulsion (HIPE) templating is a well-established method for the generation of polymeric materials with high porosity (>74%) and degree of interconnectivity. The porosity and pore size can be altered by adjusting parameters during emulsification, which affects the properties of the resulting porous structure. However, there remain challenges for the fabrication of polyHIPEs, including typically small pore sizes (∼20-50 µm) and the use of surfactants, which can limit their use in biological applications. Here, we present the use of gelatin, a natural polymer, during the formation of polyHIPE structures, through the use of two biodegradable polymers, polycaprolactone-methacrylate (PCL-M) and polyglycerol sebacate-methacrylate (PGS-M). When gelatin is used as the internal phase, it is capable of stabilising emulsions without the need for an additional surfactant. Furthermore, by changing the concentration of gelatin within the internal phase, the pore size of the resulting polyHIPE can be tuned. 5% gelatin solution resulted in the largest mean pore size, increasing from 53 µm to 80 µm and 28 µm to 94 µm for PCL-M and PGS-M respectively. In addition, the inclusion of gelatin further increased the mechanical properties of the polyHIPEs and increased the period an emulsion could be stored before polymerisation. Our results demonstrate the potential to use gelatin for the fabrication of surfactant-free polyHIPEs with macroporous structures, with potential applications in tissue engineering, environmental and agricultural industries.

Gelatin-containing porous polycaprolactone PolyHIPEs as substrates for 3D breast cancer cell culture and vascular infiltration.

Tumour survival and growth are reliant on angiogenesis, the formation of new blood vessels, to facilitate nutrient and waste exchange and, importantly, provide a route for metastasis from a primary to a secondary site. Whilst current models can ensure the transport and exchange of nutrients and waste via diffusion over distances greater than 200 µm, many lack sufficient vasculature capable of recapitulating the tumour microenvironment and, thus, metastasis. In this study, we utilise gelatin-containing polymerised high internal phase emulsion (polyHIPE) templated polycaprolactone-methacrylate (PCL-M) scaffolds to fabricate a composite material to support the 3D culture of MDA-MB-231 breast cancer cells and vascular ingrowth. Firstly, we investigated the effect of gelatin within the scaffolds on the mechanical and chemical properties using compression testing and FTIR spectroscopy, respectively. Initial in vitro assessment of cell metabolic activity and vascular endothelial growth factor expression demonstrated that gelatin-containing PCL-M polyHIPEs are capable of supporting 3D breast cancer cell growth. We then utilised the chick chorioallantoic membrane (CAM) assay to assess the angiogenic potential of cell-seeded gelatin-containing PCL-M polyHIPEs, and vascular ingrowth within cell-seeded, surfactant and gelatin-containing scaffolds was investigated via histological staining. Overall, our study proposes a promising composite material to fabricate a substrate to support the 3D culture of cancer cells and vascular ingrowth.

Elastomeric, bioadhesive and pH-responsive amphiphilic copolymers based on direct crosslinking of poly(glycerol sebacate)-co-polyethylene glycol.

Poly(glycerol sebacate) (PGS), a synthetic biorubber, is characterised by its biocompatibility, high elasticity and tunable mechanical properties; however, its inherent hydrophobicity and insolubility in water make it unsuitable for use in advanced biomaterials like hydrogels fabrication. Here, we developed new hydrophilic PGS-based copolymers that enable hydrogel formation through use of two different types of polyethylene glycol (PEG), polyethylene glycol (PEG2) or glycerol ethoxylate (PEG3), combined at different ratios. A two-step polycondensation reaction was used to produce poly(glycerol sebacate)-co-polyethylene glycol (PGS-co-PEG) copolymers that were then crosslinked thermally without the use of initiators or crosslinkers, resulting in PGS-co-PEG2 and PGS-co-PEG3 amphiphilic polymers. It has been illustrated that the properties of PGS-co-PEG copolymers can be controlled by altering the type and amount of PEG. PGS-co-PEG copolymers containing PEG ≥ 40% showed high swelling, flexibility, stretching, bioadhesion and biocompatibility, and good enzymatic degradation and mechanical properties. Also, the addition of PEG created hydrogels that demonstrated pH-responsive behaviours, which can be used for bioapplications requiring responding to physicochemical dynamics. Interestingly, PGS-co-40PEG2 and PGS-co-60PEG3 had the highest shear strengths, 340.4 ± 49.7 kPa and 336.0 ± 35.1 kPa, and these are within the range of commercially available sealants or bioglues. Due to the versatile multifunctionalities of these new copolymer hydrogels, they can have great potential in soft tissue engineering and biomedicine.