Bioprinting is a promising tool to fabricate well-organized cell-laden constructs for repair and regeneration of articular cartilage. The selection of a suitable bioink, in terms of composition and mechanical properties, is crucial for the development of viable cartilage substitutes. In this study, we focused on the use of one of the main cartilage components, hyaluronic acid (HA), to design and formulate a new bioink for cartilage tissue 3D bioprinting. Major characteristics required for this application such as printability, biocompatibility, and biodegradability were analyzed. To produce cartilage constructs with optimal mechanical properties, HA-based bioink was co-printed with polylactic acid (PLA). HA-based bioink was found to improve cell functionality by an increase in the expression of chondrogenic gene markers and specific matrix deposition and, therefore, tissue formation. These results indicate that it is a promising bioink candidate for cartilage tissue engineering based in 3D bioprinting. STATEMENT OF SIGNIFICANCE: The recent appearance of 3D printing technology has enabled great advances in the treatment of osteochondral disorders by fabrication of cartilage tissue constructs that restore and/or regenerate damaged tissue. In this attempt, the selection of a suitable biomaterial, in terms of composition and mechanical properties, is crucial. In this study, we describe for first time the development of a bioink based on the main component of cartilage, HA, with suitable biological and mechanical properties, without involving toxic procedure, and its application in cartilage tissue bioprinting. Hybrid constructs prepared by co-printing this bioink and thermoplastic polymer PLA provided an optimal niche for chondrocyte growth and maintenance as well as mechanical properties necessary to support load forces exerted in native tissue. We highlight the translation potential of this HA-based bioink in the clinical arena.

Small guanosine triphosphatases (GTPases) of the Ras superfamily are key regulators of many key cellular events such as proliferation, differentiation, cell cycle regulation, migration, or apoptosis. To control these biological responses, GTPases activity is regulated by guanine nucleotide exchange factors (GEFs), GTPase activating proteins (GAPs), and in some small GTPases also guanine nucleotide dissociation inhibitors (GDIs). Moreover, small GTPases transduce signals by their downstream effector molecules. Many studies demonstrate that small GTPases of the Ras family are involved in neurodegeneration processes. Here, in this review, we focus on the signaling pathways controlled by these small protein superfamilies that culminate in neurodegenerative pathologies, such as Alzheimer’s disease (AD) and Parkinson’s disease (PD). Specifically, we concentrate on the two most studied families of the Ras superfamily: the Ras and Rho families. We summarize the latest findings of small GTPases of the Ras and Rho families in neurodegeneration in order to highlight these small proteins as potential therapeutic targets capable of slowing down different neurodegenerative diseases.

Due to the great therapeutic interest that involves the translation of mesenchymal stromal cells (MSCs) into clinical practice, they have been widely studied as innovative drugs, in order to treat multiple pathologies. MSC-based cell therapy involves the administration of MSCs either locally or systemically into the receptor body where they can traffic and migrate towards the affected tissue and participate in the process of healing. The therapeutic effects of MSCs compromise of different mechanisms such as the functional integration of differentiated MSCs into diseased host tissue after transplantation, their paracrine support, and their impact on the regulation of both the innate and the acquired immune system. Here, we establish and provide recent advances about the principal mechanisms of action through which MSCs can perform their activity and effect as a therapeutic tool. The purpose of this review is to examine and discuss the MSCs capacity of migration, their paracrine effect, as well as MSC-mediated modifications on immune cell responses.

Osteoarthritis (OA) is the most common joint disease, generating pain, disability, and socioeconomic costs worldwide. Currently there are no approved disease-modifying drugs for OA, and safety concerns have been identified with the chronic use of symptomatic drugs. In this context, nutritional supplements and nutraceuticals have emerged as potential alternatives. Among them, collagen is being a focus of particular interest, but under the same term different types of collagens coexist with different structures, compositions, and origins, leading to different properties and potential effects. The aim of this narrative review is to generally describe the main types of collagens currently available in marketplace, focusing on those related to joint health, describing their mechanism of action, preclinical, and clinical evidence. Native and hydrolyzed collagen are the most studied collagen types for joint health. Native collagen has a specific immune-mediated mechanism that requires the recognition of its epitopes to inhibit inflammation and tissue catabolism at articular level. Hydrolyzed collagen may contain biologically active peptides that are able to reach joint tissues and exert chondroprotective effects. Although there are preclinical and clinical studies showing the safety and efficacy of food ingredients containing both types of collagens, available research suggests a clear link between collagen chemical structure and mechanism of action.

Hyaluronic acid (HA) and proteoglycans (such as dermatan sulphate (DS) and chondroitin sulphate (CS)) are the main components of the extracellular matrix of the skin, along with collagen and elastin. These components decrease with age, which implies a loss of skin moisture causing wrinkles, sagging and aging. Currently, the external and internal administration of effective ingredients that can reach the epidermis and dermis is the main alternative for combating skin aging. The objective of this work was to extract, characterise and evaluate the potential of an HA matrix ingredient to support anti-aging. The HA matrix was isolated and purified from rooster comb and characterised physicochemically and molecularly. In addition, its regenerative, anti-aging and antioxidant potential and intestinal absorption were evaluated. The results show that the HA matrix is composed of 67% HA, with an average molecular weight of 1.3 MDa; 12% sulphated glycosaminoglycans, including DS and CS; 17% protein, including collagen (10.4%); and water. The in vitro evaluation of the HA matrix’s biological activity showed regenerative properties in both fibroblasts and keratinocytes, as well as moisturising, anti-aging and antioxidant effects. Furthermore, the results suggest that the HA matrix could be absorbed in the intestine, implying a potential oral as well as topical use for skin care, either as an ingredient in a nutraceutical or a cosmetic product.