Non-Covalently Stabilized Alginate Hydrogels as Functional Cell Scaffold Material

Biopolymers are an attractive class of compounds for being used in biomedical applications as they are widely available from biomass. Their drawback is the lack of mechanical stability and the ability to tune this properly. Covalent chemical cross-linking is an often used approach but it limits usability due to legislation as well as the need of advanced and specialized knowledge by end users such as clinicians. Here, increased and tunable mechanical properties are achieved of alginate-based hydrogels with non-covalent approaches using linear polyethyleneimine (LPEI) as a polyelectrolyte rather than only multivalent metal ions (Ca2+). Gel stiffness increases with increasing LPEI content. Gel morphology changes from a thin fibrous mesh for alginate-Ca2+ to thicker fibrous networks when LPEI is introduced. The gels are able to efficiently release encapsulated small molecular dyes and the gels are able to host cells. For the cell encapsulation human skin fibroblasts (HSkF) and human bone marrow-derived mesenchymal stem cells (hBM-MSC) are used. HSkF can be successfully incorporated without diminished viability while the matrix components and gel preparation method are not compatible with hBM-MSC. The newly developed alginate-based system is regarded as a potential candidate for wound dressing materials

The response of human macrophages to 3D printed titanium antibacterial implants does not affect the osteogenic differentiation of hMSCs

Macrophage responses following the implantation of orthopaedic implants are essential for successful implant integration in the body, partly through intimate crosstalk with human marrow stromal cells (hMSCs) in the process of new bone formation. Additive manufacturing (AM) and plasma electrolytic oxidation (PEO) in the presence of silver nanoparticles (AgNPs) are promising techniques to achieve multifunctional titanium implants. Their osteoimmunomodulatory properties are, however, not yet fully investigated. Here, we studied the effects of implants with AgNPs on human macrophages and the crosstalk between hMSCs and human macrophages when co-cultured in vitro with biofunctionalised AM Ti6Al4V implants. A concentration of 0.3 g/L AgNPs in the PEO electrolyte was found to be optimal for both macrophage viability and inhibition of bacteria growth. These specimens also caused a decrease of the macrophage tissue repair related factor C-C Motif Chemokine Ligand 18 (CCL18). Nevertheless, co-cultured hMSCs could osteogenically differentiate without any adverse effects caused by the presence of macrophages that were previously exposed to the PEO (±AgNPs) surfaces. Further evaluation of these promising implants in a bony in vivo environment with and without infection is highly recommended to prove their potential for clinical use.</p

Perceptions of involvement in advance care planning and emotional functioning in patients with advanced cancer

Purpose: Advance Care Planning (ACP) is positively associated with the quality of care, but its impact on emotional functioning is ambiguous. This study investigated the association between perceptions of ACP involvement and emotional functioning in patients with advanced cancer. Methods: This study analyzed baseline data of 1,001 patients of the eQuiPe study, a prospective, longitudinal, multicenter, observational study on quality of care and quality of life in patients with advanced cancer in the Netherlands. Patients with metastatic solid cancer were asked to participate between November 2017 and January 2020. Patients’ perceptions of ACP involvement were measured by three self-administered statements. Emotional functioning was measured by the EORTC-QLQ-C30. A linear multivariable regression analysis was performed while taking gender, age, migrant background, education, marital status, and symptom burden into account. Results: The majority of patients (87%) reported that they were as much involved as they wanted to be in decisions about their future medical treatment and care. Most patients felt that their relatives (81%) and physicians (75%) were familiar with their preferences for future medical treatment and care. A positive association was found between patients’ perceptions of ACP involvement and their emotional functioning (b=0.162, p<0.001, 95%CI[0.095;0.229]) while controlling for relevant confounders. Conclusions: Perceptions of involvement in ACP are positively associated with emotional functioning in patients with advanced cancer. Future studies are needed to further investigate the effect of ACP on emotional functioning. Trial registration number: NTR6584 Date of registration: 30 June 2017 Implications for Cancer Survivors: Patients’ emotional functioning might improve from routine discussions regarding goals of future care. Therefore, integration of ACP into palliative might be promising

Effects of silver nanoparticle- containing 3D printed antibacterial implants on macrophages

Orthopedic implants used for total joint replacements are under a high clinical demand. Although most total joint replacements are successful, premature failures are still affecting tens of thousands of people annually. The major causes of implant failure are aseptic loosening and bacterial infections. To overcome these issues, multifunctional biomaterials that can on one hand battle implant associated infections (IAI), while on the other hand enhance osseointergration are being researched. Additive manufacturing and surface modification of titanium and its alloys are very promising strategies to enhance osseointergration, as the micro-architectural structures generated by these techniques have been shown to improve bone tissue integration. However, bacteria can more easily evade defense mechanisms in porous structures. To battle possible IAI, silver nanoparticles (AgNPs) can be incorporated into the surface. However, it is crucial that such antibacterial mechanisms do not interfere with tissue regeneration processes or impact cells that play a key role in regulating bone regeneration, such as macrophages. Therefore, the aim of this study was to generate an implant which could inhibit bacterial activity, while preventing adverse effects towards macrophages. 3D printed Ti-6Al-4V implants were modified by plasma electrolytic oxidation (PEO), during which different concentrations of AgNPs were incorporated into the surface. Surfaces were characterized by scanning electron microscopy (SEM) and energy- dispersive X-ray (EDX). The viability of human mesenchymal stem cells, mouse J774A.1 macrophages and primary human macrophages was determined following the culture of each cell type on the surface of implants. Additionally, inflammatory gene and secreted protein levels were determined following the culture of human primary macrophages on the surface of the most promising implant. Finally, antibacterial activity of these implants was investigated. Implants that were surface modified in the presence of 0.3 g AgNPs/L were identified as the most promising implant to support cellular viability. Furthermore, human macrophages cultured on the surface of PEO + 0.3 g AgNPs/L implants had comparable inflammatory gene expression and cytokine production levels compared to cells cultured on implants not containing AgNPS. Moreover, metabolic activity assessment of S. aureus and E. coli in the presence of PEO + 0.3 g AgNPs/L implants showed that E. coli was affected, while S. aureus was not. Interestingly, SEM images showed none of the bacteria were able to colonize the surface, highlighting the generation of an implant which can inhibit bacterial colonization, while not showing adverse effects towards macrophages.Biomedical Engineerin

Bereaved relatives’ quality of life before and during the COVID-19 pandemic: Results of the prospective, multicenter, observational eQuiPe study

Background: The death of a loved one is considered as one of the most stressful life events. During the COVID-19 pandemic, grief processes are potentially affected by measures such as social distancing and self-quarantine. Aim: The aim of this study was to give insight in the impact of the COVID-19 pandemic on quality of life, social support, and self-care of bereaved relatives of people with advanced cancer in order to evaluate whether care for bereaved relatives during the COVID-19 pandemic should be improved. Design: A cross-sectional analysis using data from bereaved relatives of a prospective, longitudinal, multicenter, observational study on quality of care and quality of life of people with advanced cancer and their (bereaved) relatives (eQuiPe). Setting/participants: Quality of life, social support, and self-care of bereaved relatives who completed a questionnaire within 3–6 months after their relative died during COVID-19 (April-November 2020) were compared with bereaved relatives who completed this questionnaire pre-COVID-19 (April-November 2019). Results: Ninety-one bereaved relatives were included in the analysis, 44 bereaved relatives completed the questionnaire pre-COVID-19 and 47 during COVID-19. The median age of the participants was 65 (IQR = 14) years and 58% were female. There were no significant differences between the pre-COVID-19 and during COVID-19 bereaved relatives in quality of life (68 vs 69), social support (17 vs 18), and self-care (20 vs 19). Conclusions: On the short-term, the COVID-19 pandemic did not have significant impact on bereaved relatives’ wellbeing. However, long-term impact of the pandemic on their wellbeing should be assessed

Bereaved relatives’ quality of life before and during the COVID-19 pandemic:Results of the prospective, multicenter, observational eQuiPe study

Background: The death of a loved one is considered as one of the most stressful life events. During the COVID-19 pandemic, grief processes are potentially affected by measures such as social distancing and self-quarantine. Aim: The aim of this study was to give insight in the impact of the COVID-19 pandemic on quality of life, social support, and self-care of bereaved relatives of people with advanced cancer in order to evaluate whether care for bereaved relatives during the COVID-19 pandemic should be improved. Design: A cross-sectional analysis using data from bereaved relatives of a prospective, longitudinal, multicenter, observational study on quality of care and quality of life of people with advanced cancer and their (bereaved) relatives (eQuiPe). Setting/participants: Quality of life, social support, and self-care of bereaved relatives who completed a questionnaire within 3–6 months after their relative died during COVID-19 (April-November 2020) were compared with bereaved relatives who completed this questionnaire pre-COVID-19 (April-November 2019). Results: Ninety-one bereaved relatives were included in the analysis, 44 bereaved relatives completed the questionnaire pre-COVID-19 and 47 during COVID-19. The median age of the participants was 65 (IQR = 14) years and 58% were female. There were no significant differences between the pre-COVID-19 and during COVID-19 bereaved relatives in quality of life (68 vs 69), social support (17 vs 18), and self-care (20 vs 19). Conclusions: On the short-term, the COVID-19 pandemic did not have significant impact on bereaved relatives’ wellbeing. However, long-term impact of the pandemic on their wellbeing should be assessed

Emotional functioning during bereavement after the death of patients with advanced cancer and associated factors

Objective The death of a loved one is considered to be the most stressful of all life events. However, the impact of bereavement on quality of life varies between individuals. The aim of our study was to assess emotional functioning (EF), which is a domain of quality of life, of bereaved relatives after the death of their loved one and its associated factors. Method A prospective, longitudinal, multicenter, observational study on quality of care and quality of life of patients with advanced cancer and their relatives was conducted (eQuiPe). The association between EF of relatives during bereavement and the following factors was investigated: gender, type of relationship, educational level, pre-bereavement emotional and social functioning and global quality of life, social support pre- and during bereavement, anticipatory complicated grief, support of healthcare professionals during bereavement, age of patient and bereaved relative and duration of survival after primary cancer diagnosis. Results 150 bereaved relatives completed the bereavement questionnaire. In 41% of the bereaved relatives EF was ≤71, indicating clinically relevant low EF. Multivariable logistic regression showed that females experienced more often emotional problems (OR = 2.82). Emotional functioning pre-bereavement (OR = 0.96) and social support during bereavement (OR = 0.97) were associated with low EF during bereavement. Conclusions Almost half of the bereaved relatives of patients with advanced cancer experienced low EF and this was associated with low EF pre-bereavement and low social support during bereavement. Support for relatives should be initiated before the patient's death. Future research is needed to investigate the impact of such support on relatives' wellbeing during bereavement

Emotional functioning during bereavement after the death of patients with advanced cancer and associated factors

Objective: The death of a loved one is considered to be the most stressful of all life events. However, the impact of bereavement on quality of life varies between individuals. The aim of our study was to assess emotional functioning (EF), which is a domain of quality of life, of bereaved relatives after the death of their loved one and its associated factors. Method: A prospective, longitudinal, multicenter, observational study on quality of care and quality of life of patients with advanced cancer and their relatives was conducted (eQuiPe). The association between EF of relatives during bereavement and the following factors was investigated: gender, type of relationship, educational level, pre-bereavement emotional and social functioning and global quality of life, social support pre- and during bereavement, anticipatory complicated grief, support of healthcare professionals during bereavement, age of patient and bereaved relative and duration of survival after primary cancer diagnosis. Results: 150 bereaved relatives completed the bereavement questionnaire. In 41% of the bereaved relatives EF was ≤71, indicating clinically relevant low EF. Multivariable logistic regression showed that females experienced more often emotional problems (OR = 2.82). Emotional functioning pre-bereavement (OR = 0.96) and social support during bereavement (OR = 0.97) were associated with low EF during bereavement. Conclusions: Almost half of the bereaved relatives of patients with advanced cancer experienced low EF and this was associated with low EF pre-bereavement and low social support during bereavement. Support for relatives should be initiated before the patient's death. Future research is needed to investigate the impact of such support on relatives' wellbeing during bereavement

Trajectories of emotional functioning and experienced care of relatives in the last year of life of patients with advanced cancer:A longitudinal analysis of the eQuiPe study

Objective Advanced cancer has a major impact on both patients and their relatives. To allow for personalized support, it is important to recognize which relatives will experience a decline in emotional functioning during the patient's last year of life, when this decline will occur, and what factors are associated with it. This study aimed to examine the trajectory of emotional functioning of relatives during that time and the characteristics associated with changes in this trajectory.MethodsA prospective, longitudinal, multicenter, observational study in patients with advanced cancer and their relatives was conducted (eQuiPe). We analyzed relatives' changes in emotional functioning in the patient's last year using the EORTC QLQ-C30 and assessed associations with sociodemographic and care characteristics using multivariable mixed-effects analysis.Results409 relatives completed &gt;= 1 questionnaires during the patient's last year of life. Mean age was 64 years, 61% were female and 75% were the patient's partner. During this year, mean emotional functioning declined significantly over time from 73.9 to 64.6 (p = 0.023, effect size = 0.43). The type of relationship between relatives and patients (p = 0.002), patient' sleep problems (p = 0.033), and continuity of care (p = 0.002) were significantly associated with changes in emotional functioning.ConclusionsRelatives' emotional functioning declined during the patient's last year of life. Support for them, especially partners and relatives of patients with sleep problems, is important. Relatives who experienced more continuity of care had a less steep decline in emotional functioning

Trajectories of emotional functioning and experienced care of relatives in the last year of life of patients with advanced cancer: A longitudinal analysis of the eQuiPe study

Objective: Advanced cancer has a major impact on both patients and their relatives. To allow for personalized support, it is important to recognize which relatives will experience a decline in emotional functioning during the patient's last year of life, when this decline will occur, and what factors are associated with it. This study aimed to examine the trajectory of emotional functioning of relatives during that time and the characteristics associated with changes in this trajectory. Methods: A prospective, longitudinal, multicenter, observational study in patients with advanced cancer and their relatives was conducted (eQuiPe). We analyzed relatives' changes in emotional functioning in the patient's last year using the EORTC QLQ-C30 and assessed associations with sociodemographic and care characteristics using multivariable mixed-effects analysis. Results: 409 relatives completed ≥1 questionnaires during the patient's last year of life. Mean age was 64 years, 61% were female and 75% were the patient's partner. During this year, mean emotional functioning declined significantly over time from 73.9 to 64.6 (p = 0.023, effect size = 0.43). The type of relationship between relatives and patients (p = 0.002), patient’ sleep problems (p = 0.033), and continuity of care (p = 0.002) were significantly associated with changes in emotional functioning. Conclusions: Relatives' emotional functioning declined during the patient's last year of life. Support for them, especially partners and relatives of patients with sleep problems, is important. Relatives who experienced more continuity of care had a less steep decline in emotional functioning