Design and Characterization of Biomimetic Hybrid Construct Based on Hyaluronic Acid and Alginate Bioink for Regeneration of Articular Cartilage.

Three-dimensional bioprinting technology has enabled great advances in the treatment of articular cartilage (AC) defects by the biofabrication of biomimetic constructs that restore and/or regenerate damaged tissue. In this sense, the selection of suitable cells and biomaterials to bioprint constructs that mimic the architecture, composition, and functionality of the natural extracellular matrix (ECM) of the native tissue is crucial. In the present study, a novel cartilage-like biomimetic hybrid construct (CBC) was developed by 3D bioprinting to facilitate and promote AC regeneration.

Design and evaluation of a bilayered dermal/hypodermal 3D model using a biomimetic hydrogel formulation.

Due to the limitations of the current skin wound treatments, it is highly valuable to have a wound healing formulation that mimics the extracellular matrix (ECM) and mechanical properties of natural skin tissue. Here, a novel biomimetic hydrogel formulation has been developed based on a mixture of Agarose-Collagen Type I (AC) combined with skin ECM-related components: Dermatan sulfate (DS), Hyaluronic acid (HA), and Elastin (EL) for its application in skin tissue engineering (TE). Different formulations were designed by combining AC hydrogels with DS, HA, and EL.

Human mesenchymal stromal cells-laden crosslinked hyaluronic acid-alginate bioink for 3D bioprinting applications in tissue engineering.

Three-dimensional (3D) bioprinting is considered one of the most advanced tools to build up materials for tissue engineering. The aim of this work was the design, development and characterization of a bioink composed of human mesenchymal stromal cells (hMSC) for extrusion through nozzles to create these 3D structures that might potentially be apply to replace the function of damaged natural tissue. In this study, we focused on the advantages and the wide potential of biocompatible biomaterials, such as hyaluronic acid and alginate for the inclusion of hMSC.

Development and characterization of a poloxamer hydrogel composed of human mesenchymal stromal cells (hMSCs) for reepithelization of skin injuries.

Wound healing is a natural physiological reaction to tissue injury. Hydrogels show attractive advantages in wound healing not only due to their biodegradability, biocompatibility and permeability but also because provide an excellent environment for cell migration and proliferation. The main objective of the present study was the design and characterization of a hydrogel loaded with human mesenchymal stromal cells (hMSCs) for use in would healing of superficial skin injures.

Collagen Supplementation for Joint Health: The Link between Composition and Scientific Knowledge.

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.

Preservation of critical quality attributes of mesenchymal stromal cells in 3D bioprinted structures by using natural hydrogel scaffolds.

Three dimensional (3D) bioprinting is an emerging technology that enables complex spatial modeling of cell-based tissue engineering products, whose therapeutic potential in regenerative medicine is enormous. However, its success largely depends on the definition of a bioprintable zone, which is specific for each combination of cell-loaded hydrogels (or bioinks) and scaffolds, matching the mechanical and biological characteristics of the target tissue to be repaired. Therefore proper adjustment of the bioink formulation requires a compromise between: (i) the maintenance of cellular critical quality attributes (CQA) within a defined range of specifications to cell component, and (ii) the mechanical characteristics of the printed tissue to biofabricate.

A Novel Hyaluronic Acid Matrix Ingredient with Regenerative, Anti-Aging and Antioxidant Capacity.

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.

Progress in 3D Bioprinting Technology for Osteochondral Regeneration.

Osteochondral injuries can lead to osteoarthritis (OA). OA is characterized by the progressive degradation of the cartilage tissue together with bone tissue turnover. Consequently, joint pain, inflammation, and stiffness are common, with joint immobility and dysfunction being the most severe symptoms.

Chondro-Inductive b-TPUe-Based Functionalized Scaffolds for Application in Cartilage Tissue Engineering.

Osteoarthritis is a disease with a great socioeconomic impact and mainly affects articular cartilage, a tissue with reduced self-healing capacity. In this work, 3D printed 1,4 butanediol thermoplastic polyurethane (b-TPUe) scaffolds are functionalized and infrapatellar mesenchymal stem cells are used as the cellular source. Since b-TPUe is a biomaterial with mechanical properties similar to cartilage, but it does not provide the desired environment for cell adhesion, scaffolds are functionalized with two methods, one based on collagen type I and the other in 1-pyrenebutiric acid (PBA) as principal components.

Biofabrication approaches and regulatory framework of metastatic tumor-on-a-chip models for precision oncology.

The complexity of the tumor microenvironment (TME) together with the development of the metastatic process are the main reasons for the failure of conventional anticancer treatment. In recent years, there is an increasing need to advance toward advanced in vitro models of cancer mimicking TME and simulating metastasis to understand the associated mechanisms that are still unknown, and to be able to develop personalized therapy. In this review, the commonly used alternatives and latest advances in biofabrication of tumor-on-chips, which allow the generation of the most sophisticated and optimized models for recapitulating the tumor process, are presented.

Advances in spray products for skin regeneration.

To date, skin wounds are still an issue for healthcare professionals. Although numerous approaches have been developed over the years for skin regeneration, recent advances in regenerative medicine offer very promising strategies for the fabrication of artificial skin substitutes, including 3D bioprinting, electrospinning or spraying, among others. In particular, skin sprays are an innovative technique still under clinical evaluation that show great potential for the delivery of cells and hydrogels to treat acute and chronic wounds.

Chondroitin and Dermatan Sulfate Bioinks for 3D Bioprinting and Cartilage Regeneration.

Cartilage is a connective tissue which a limited capacity for healing and repairing. In this context, osteoarthritis (OA) disease may be developed with high prevalence in which the use of scaffolds may be a promising treatment. In addition, three-dimensional (3D) bioprinting has become an emerging additive manufacturing technology because of its rapid prototyping capacity and the possibility of creating complex structures.

An Overview on the Manufacturing of Functional and Mature Cellular Skin Substitutes.

There are different types of skin diseases due to chronic injuries that impede the natural healing process of the skin. Tissue engineering has focused on the development of bioengineered skin or skin substitutes that cover the wound, providing the necessary care to restore the functionality of injured skin. There are two types of substitutes: acellular skin substitutes, which offer a low response to the body, and cellular skin substitutes (CSSs), which incorporate living cells and appear as a great alternative in the treatment of skin injuries due to their greater interaction and integration with the rest of the body.

Sphingolipid extracts enhance gene delivery of cationic lipid vesicles into retina and brain.

The aim was to evaluate relevant biophysic processes related to the physicochemical features and gene transfection mechanism when sphingolipids are incorporated into a cationic niosome formulation for non-viral gene delivery to central nervous system. For that, two formulations named niosphingosomes and niosomes devoid of sphingolipid extracts, as control, were developed by the oil-in water emulsion technique. Both formulations and the corresponding complexes, obtained upon the addition of the reporter EGFP plasmid, were physicochemically and biologically characterized and evaluated.

Modulation of Conductivity of Alginate Hydrogels Containing Reduced Graphene Oxide through the Addition of Proteins.

Modifying hydrogels in order to enhance their conductivity is an exciting field with applications in cardio and neuro-regenerative medicine. Therefore, we have designed hybrid alginate hydrogels containing uncoated and protein-coated reduced graphene oxide (rGO). We specifically studied the adsorption of three different proteins, BSA, elastin, and collagen, and the outcomes when these protein-coated rGO nanocomposites are embedded within the hydrogels.

Validation of the 1,4-butanediol thermoplastic polyurethane as a novel material for 3D bioprinting applications.

Tissue engineering (TE) seeks to fabricate implants that mimic the mechanical strength, structure, and composition of native tissues. Cartilage TE requires the development of functional personalized implants with cartilage-like mechanical properties capable of sustaining high load-bearing environments to integrate into the surrounding tissue of the cartilage defect. In this study, we evaluated the novel 1,4-butanediol thermoplastic polyurethane elastomer (b-TPUe) derivative filament as a 3D bioprinting material with application in cartilage TE.

Evaluation of Glycerylphytate Crosslinked Semi- and Interpenetrated Polymer Membranes of Hyaluronic Acid and Chitosan for Tissue Engineering.

In the present study, semi- and interpenetrated polymer network (IPN) systems based on hyaluronic acid (HA) and chitosan using ionic crosslinking of chitosan with a bioactive crosslinker, glycerylphytate (GPhy), and UV irradiation of methacrylate were developed, characterized and evaluated as potential supports for tissue engineering. Semi- and IPN systems showed significant differences between them regarding composition, morphology, and mechanical properties after physicochemical characterization. Dual crosslinking process of IPN systems enhanced HA retention and mechanical properties, providing also flatter and denser surfaces in comparison to semi-IPN membranes.

Small GTPases of the Ras and Rho Families Switch on/off Signaling Pathways in Neurodegenerative Diseases.

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.

BSA- and Elastin-Coated GO, but Not Collagen-Coated GO, Enhance the Biological Performance of Alginate Hydrogels.

The use of embedded cells within alginate matrices is a developing technique with great clinical applications in cell-based therapies. However, one feature that needs additional investigation is the improvement of alginate-cells viability, which could be achieved by integrating other materials with alginate to improve its surface properties. In recent years, the field of nanotechnology has shown the many properties of a huge number of materials.

Role of Mesenchymal Stromal Cells as Therapeutic Agents: Potential Mechanisms of Action and Implications in Their Clinical Use.

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.

Bio-inspired hydrogel composed of hyaluronic acid and alginate as a potential bioink for 3D bioprinting of articular cartilage engineering constructs.

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.

An overview of international regulatory frameworks for mesenchymal stromal cell-based medicinal products: From laboratory to patient.

Human mesenchymal stromal cells (hMSCs) are emerging as one of the most important cell types in advanced therapies and regenerative medicine due to their great therapeutic potential. The development of hMSC-based products focuses on the use of hMSCs as biological active substances, and they are considered medicinal products by the primary health agencies worldwide. Due to their regulatory status, the development of hMSC-based products is regulated by specific criteria that range from the design phase, nonclinical studies, clinical studies, to the final registration and approval.

A Worldwide Overview of Regulatory Frameworks for Tissue-Based Products.

Over the past decades, a wide range of tissue-based products (TBPs) have emerged as new therapeutic alternatives to conventional approaches, giving an opportunity to treat pathologies that have not been cured yet. TBPs are constituted by living/nonliving and genetically/nongenetically modified cells or tissues, which might be combined with materials that support their structure, molecules that favor the cellular environment, and even medical devices to create functional substitutes. These medicinal products are used for the repair, replacement, restoration, or regeneration of a damaged tissue in the patient.

Principal Criteria for Evaluating the Quality, Safety and Efficacy of hMSC-Based Products in Clinical Practice: Current Approaches and Challenges.

Human Mesenchymal Stem Cells (hMSCs) play an important role as new therapeutic alternatives in advanced therapies and regenerative medicine thanks to their regenerative and immunomodulatory properties, and ability to migrate to the exact area of injury. These properties have made hMSCs one of the more promising cellular active substances at present, particularly in terms of the development of new and innovative hMSC-based products. Currently, numerous clinical trials are being conducted to evaluate the therapeutic activity of hMSC-based products on specific targets.

Design and evaluation of mesenchymal stem cells seeded chitosan/glycosaminoglycans quaternary hydrogel scaffolds for wound healing applications.

The main goal of this study was the design, development and characterization of a chitosan based scaffolding substrate including three glycosaminoglycans and collagen to provide an optimal microenvironment for human mesemchymal stem cells isolated from adipose tissue (hMSCs). Chitosan scaffolds provide a moist wound environment which promotes healing and epidermal regeneration. Furthermore, the importance of extracellular molecules such as glycosaminoglycans in wound healing makes them essential ingredients in these types of formulations.