Extracellular vesicles and their current role in cancer immunotherapy

Extracellular vesicles (EVs) are natural particles formed by the lipid bilayer and released from almost all cell types to the extracellular environment both under physiological conditions and in presence of a disease. EVs are involved in many biological processes including intercellular communication, acting as natural carriers in the transfer of various biomolecules such as DNA, various RNA types, proteins and different phospholipids. Thanks to their transfer and targeting abilities, they can be employed in drug and gene delivery and have been proposed for the treatment of different diseases, including cancer. Recently, the use of EVs as biological carriers has also been extended to cancer immunotherapy. This new technique of cancer treatment involves the use of EVs to transport molecules capable of triggering an immune response to damage cancer cells. Several studies have analyzed the possibility of using EVs in new cancer vaccines, which represent a particular form of immunotherapy. In the literature there are only few publications that systematically group and collectively discuss these studies. Therefore, the purpose of this review is to illustrate and give a partial reorganization to what has been produced in the literature so far. We provide basic notions on cancer immunotherapy and describe some clinical trials in which therapeutic cancer vaccines are tested. We thus focus attention on the potential of EV-based therapeutic vaccines in the treatment of cancer patients, overviewing the clinically relevant trials, completed or still in progress, which open up new perspectives in the fight against cancer

Sex differences in heel pad stiffness during in vivo loading and unloading

Due to conflicting data from previous studies a new methodological approach to evaluate heel pad stiffness and soft tissue deformation has been developed. The purpose of this study was to compare heel pad (HP) stiffness in both limbs between males and females during a dynamic unloading and loading activity. Ten males and 10 females volunteered to perform three dynamic trials to unload and load the HP. The dynamic protocol consisted of three continuous phases: foot flat (baseline phase), bilateral heel raise (unloading phase) and foot flat (loading phase) with each phase lasting two seconds. Six retroreflective markers (3 mm) were attached to the skin of the left and right heels using a customised marker set. Three-dimensional motion analysis cameras synchronised with force plates collected the kinematic and kinetic data throughout the trials. Three-way repeated measures ANOVA together with a Bonferroni post hoc test were applied to the stiffness and marker displacement datasets. On average, HP stiffness was higher in males than females during the loading and unloading phases. ANOVA results revealed no significant differences for the stiffness and displacement outputs with respect to sex, sidedness or phase interactions (p > .05) in the X, Y and Z directions. Irrespective of direction, there were significant differences in stiffness between the baseline and unloading conditions (p .116). Finally, females portrayed lower levels of mean HP stiffness whereas males had stiffer heels particularly in the vertical direction (Z) when the HP was both unloaded and loaded. High HP stiffness values and very small marker displacements could be valuable indicators for the risk of pathological foot conditions

Polyplex-loaded hydrogels for local gene delivery to human dermal fibroblasts

Impaired cutaneous healing leading to chronic wounds affects between 2 and 6% of the total population in most developed countries and it places a substantial burden on healthcare budgets. Current treatments involving antibiotic dressings and mechanical debridement are often not effective, causing severe pain, emotional distress, and social isolation in patients for years or even decades, ultimately resulting in limb amputation. Alternatively, gene therapy (such as mRNA therapies) has emerged as a viable option to promote wound healing through modulation of gene expression. However, protecting the genetic cargo from degradation and efficient transfection into primary cells remain significant challenges in the push to clinical translation. Another limiting aspect of current therapies is the lack of sustained release of drugs to match the therapeutic window. Herein, we have developed an injectable, biodegradable and cytocompatible hydrogel-based wound dressing that delivers poly(β-amino ester)s (pBAEs) nanoparticles in a sustained manner over a range of therapeutic windows. We also demonstrate that pBAE nanoparticles, successfully used in previous in vivo studies, protect the mRNA load and efficiently transfect human dermal fibroblasts upon sustained release from the hydrogel wound dressing. This prototype wound dressing technology can enable the development of novel gene therapies for the treatment of chronic wounds

Bone and Cartilage Regeneration: A New Challenge for Materials Science

Bone and cartilage regeneration is still a challenge in medicine, due to the high complexity of these tissues. Materials science plays an important role in the future of the bone and cartilage restoration research. Its main goal is the development of biomaterials able to promote bone and cartilage healing. This paper gives a general view of the problem and the state of the present research about bone and cartilage regeneration. It also shows the need for the development of a global approach, which bears in mind all the involved parts of the cartilage/bone system, as well as its different organization levels