The tumor microenvironment (TME), composed of and influenced by a heterogeneous set of cancer cells and an extracellular matrix, plays a crucial role in cancer progression. The biophysical aspects of the TME (namely, its architecture and mechanics) regulate interactions and spatial distributions of cancer cells and immune cells. In this review, we discuss the factors of the TME-notably, the extracellular matrix, as well as tumor and stromal cells-that contribute to a pro-tumor, immunosuppressive response. We then discuss the ways in which cells of the innate and adaptive immune systems respond to tumors from both biochemical and biophysical perspectives, with increased focus on CD8+ and CD4+ T cells. Building upon this information, we turn to immune-based antitumor interventions-specifically, recent biophysical breakthroughs aimed at improving CAR-T cell therapy.
Hyaluronan (HA) is a natural biodegradable biopolymer; its biological functions include cell adhesion, cell proliferation, and differentiation as well as decreasing inflammation, angiogenesis, and regeneration of damaged tissue. This makes it a suitable candidate for fabricating nanomaterials with potential use in tissue engineering. However, HA nanofiber production is restricted due to the high viscosity, low evaporation rate, and high surface tension of HA solutions. Here, hybrids in the form of continuous and randomly aligned polyvinyl alcohol (PVA)-(HA)-siloxane nanofibers were obtained using an electrospinning process. PVA-HA fibers were crosslinked by a 3D siloxane organic-inorganic matrix via sol-gel that restricts natural hydrophilicity and stiffens the structure. The hybrid nanofiber mats were characterized by FT-IR, micro-Raman spectroscopy, SEM, and biological properties. The PVA/HA ratio influenced the morphology of the hybrid nanofibers. Nanofibers with high PVA content (10PVA-8 and 10PVA-10) form mats with few beaded nanofibers, while those with high HA content (5PVA-8 and 5PVA-10) exhibit mats with mound patterns formed by "ribbon-like" nanofibers. The hybrid nanofibers were used as mats to support osteoblast growth, and they showed outstanding biological properties supporting cell adhesion, cell proliferation, and cell differentiation. Importantly, the 5PVA-8 mats show 3D spherical osteoblast morphology; this suggests the formation of tissue growth. These novel HA-based nanomaterials represent a relevant advance in designing nanofibers with unique properties for potential tissue regeneration.
Importance: Chronic obstructive pulmonary disease (COPD) is a respiratory condition that is associated with significant health and economic burden worldwide. Previous studies assessed the global current-day prevalence of COPD, but to better facilitate resource planning and intervention development, long-term projections are needed. Objective: To assess the global burden of COPD through 2050, considering COPD risk factors. Design, Setting, and Participants: In this modeling study, historical data on COPD prevalence was extracted from a recent meta-analysis on 2019 global COPD prevalence, and 2010 to 2018 historical prevalence was estimated using random-effects meta-analytical models. COPD risk factor data were obtained from the Global Burden of Disease database. Main Outcomes and Measures: To project global COPD prevalence to 2050, generalized additive models were developed, including smoking prevalence, indoor and outdoor air pollution, and development indices as predictors, and stratified by age, sex, and World Bank region. Results: The models estimated that the number of COPD cases globally among those aged 25 years and older will increase by 23% from 2020 to 2050, approaching 600 million patients with COPD globally by 2050. Growth in the burden of COPD was projected to be the largest among women and in low- and middle-income regions. The number of female cases was projected to increase by 47.1% (vs a 9.4% increase for males), and the number of cases in low- and middle-income regions was expected to be more than double that of high-income regions by 2050. Conclusions and Relevance: In this modeling study of future COPD burden, projections indicated that COPD would continue to affect hundreds of millions of people globally, with disproportionate growth among females and in low-middle income regions through 2050. Further research, prevention, and advocacy are needed to address these issues so that adequate preparation and resource allocation can take place.
Air Pollution , Pulmonary Disease, Chronic Obstructive , Respiration Disorders , Male , Humans , Female , Pulmonary Disease, Chronic Obstructive/epidemiology , Air Pollution/adverse effects , Prevalence , Smoking
Hybrid materials have been studied because in these materials the properties of organic components, such as elasticity and biodegradability, could be combined with the properties of inorganic components, such as good biological response, thereby transforming them into a single material with improved properties. In this work, Class I hybrid materials based on polyester-urea-urethanes and titania were obtained using the modified sol-gel method. This was corroborated using the FT-IR and Raman techniques which highlighted the formation of hydrogen bonds and the presence of Ti-OH groups in the hybrid materials. In addition, the mechanical and thermal properties and degradability were measured using techniques, such as Vickers hardness, TGA, DSC, and hydrolytic degradation; these properties could be tailored according to hybridization between both organic and inorganic components. The results show that Vickers hardness increased by 20% in hybrid materials as compared to polymers; also, the surface hydrophilicity increases in the hybrid materials, improving their cell viability. Furthermore, cytotoxicity in vitro test was carried out using osteoblast cells for intended biomedical applications and they showed non-cytotoxic behavior.
Isolated vertebral mestastases can be successfully treated by surgical removal of the affected vertebral body and stabilization with alloplastic material. The bone union between the upper and lower vertebra is expected, yet a relatively high rate of a non-union has been reported. In case of infection, bone consolidation is altered, and removal of alloplastic material is recommended, which decreases spinal stability and is a devastating complication. This case report of delayed infection and exposure of posterior hardware after thoracic vertebrectomy without an interbody osseous union, authors present a successful treatment with vascularized rib flaps through an anterior approach followed by hardware removal.
In this study, an in vitro evaluation of the human osteoblasts response to Organically Modified Silicate (ORMOSIL) biomaterials was conducted. These materials were synthetized by sol-gel process being modified with zirconia (ZrO2) and/or Ca2+. The materials were immersed into phosphate buffer solution (PBS) in order to test precipitation of mimetic apatite-like on their surfaces. ORMOSILs were characterized by SEM, FT-IR and X-RD analysis. The response of osteoblast to ORMOSILs was analyzed as a measure of cell adhesion, proliferation and differentiation. The results showed that the addition of Ca2+ ions modifies the surface morphology of ORMOSILs by forming precipitates of mimetic apatite-like with cauliflower and scales morphologies. On the other hand, biological results suggest that the incorporation of zirconia to ORMOSILs increases their ability to support cell adhesion and proliferation. However, the inclusion of both zirconia and Ca2+ in the ORMOSILs decreases their biological compatibility by showing less cell proliferation and lower osteonectin expression, a protein related to osteoblasts. The unfavorable effect of Ca2+ on cell proliferation and cell viability could be due to its ability to induce the formation of mimetic apatite-like with incompatible morphology. The analysis of other proteins related to bone formation on ORMOSIL-Zr and ORMOSIL-Zr-Ca surfaces demonstrated clear expression of osteopontin and osteocalcin in cells growth. In the case of ORMOSIL-Zr, the expression of osteonectin occurred at early stages while the expression of osteopontin and osteocalcin begun at later stages, indicating a switch from an early to a mature stage being stimulated by the biomaterial. Together, these results highlight the important role of zirconia and Ca2+ ions in the composition of materials regulating their biocompatibility when used as scaffolds in bone regeneration.
Bone Regeneration , Cell Differentiation , Cell Proliferation , Coated Materials, Biocompatible/chemistry , Materials Testing , Osteoblasts/metabolism , Tissue Scaffolds/chemistry , Zirconium/chemistry , Cell Adhesion , Cell Line, Tumor , Humans , Osteoblasts/cytology
The aims of this paper are: (1) to review the current state of the art in the field of cartilage substitution and regeneration; (2) to examine the patented biomaterials being used in preclinical and clinical stages; (3) to explore the potential of polymeric hydrogels for these applications and the reasons that hinder their clinical success. The studies about hydrogels used as potential biomaterials selected for this review are divided into the two major trends in tissue engineering: (1) the use of cell-free biomaterials; and (2) the use of cell seeded biomaterials. Preparation techniques and resulting hydrogel properties are also reviewed. More recent proposals, based on the combination of different polymers and the hybridization process to improve the properties of these materials, are also reviewed. The combination of elements such as scaffolds (cellular solids), matrices (hydrogel-based), growth factors and mechanical stimuli is needed to optimize properties of the required materials in order to facilitate tissue formation, cartilage regeneration and final clinical application. Polymer combinations and hybrids are the most promising materials for this application. Hybrid scaffolds may maximize cell growth and local tissue integration by forming cartilage-like tissue with biomimetic features.
Orbital mesenchymal chondrosarcoma is a very uncommon lesion of the bone and extraskeletal tissue. To our knowledge, approximately 30 cases have been described. We present the case of a 52-year-old male who presented with a history of progressive proptosis and chemosis of the right eye caused by an orbital tumor. He underwent exenteration of the right orbit, and the histological examination revealed a mesenchymal orbital chondrosarcoma. This paper attempts to describe a rare entity that should be considered in the differential diagnosis of calcified orbital lesions, especially in young adults. Complete removal of the tumor is the mainstay of treatment, but adjuvant radiation therapy and chemotherapy should be considered.
