The Importance of Hyaluronic Acid in Biological Systems

Hyaluronic acid (HA) is a crucial component of the extracellular matrix, found abundantly in connective tissues, skin, and synovial fluid. Its unique properties, including hydration capacity and viscoelasticity, play pivotal roles in tissue hydration, lubrication, and wound healing. Despite its ubiquitous presence, the specific mechanisms underlying its diverse biological functions remain the subject of ongoing research. Studies have elucidated HA's involvement in various physiological processes, such as cell proliferation, migration, and differentiation. Its interaction with cell surface receptors modulates signaling pathways implicated in tissue repair and inflammation regulation. Moreover, HA's rheological properties contribute to joint lubrication, facilitating smooth movement and preventing cartilage degradation. Understanding the multifaceted roles of HA holds significant implications for biomedical applications. Its therapeutic potential spans from skincare formulations to regenerative medicine and drug delivery systems. Targeting HA metabolism presents novel strategies for treating conditions like osteoarthritis, dry eye syndrome, and dermal aging. Continued exploration of HA biology promises exciting avenues for scientific advancement and clinical innovation. Emerging technologies, such as biomaterial engineering and nanomedicine, offer opportunities to tailor HA-based interventions for enhanced efficacy and targeted delivery. Additionally, investigating HA's interplay with the immune system could uncover new immunomodulatory therapies. In conclusion, the importance of hyaluronic acid in biological systems is indisputable, given its indispensable roles in tissue homeostasis and repair. By deciphering its intricate mechanisms of action, researchers pave the way for groundbreaking advancements in medicine and biotechnology. Harnessing the therapeutic potential of HA stands poised to revolutionize healthcare, offering solutions to a myriad of pathological conditions and enhancing quality of life.&nbsp

Advantages of additive manufacturing for biomedical applications of polyhydroxyalkanoates

In recent years, biopolymers have been attracting the attention of researchers and special-ists from different fields, including biotechnology, material science, engineering, and medicine. The reason is the possibility of combining sustainability with scientific and technological progress. This is an extremely broad research topic, and a distinction has to be made among different classes and types of biopolymers. Polyhydroxyalkanoate (PHA) is a particular family of polyesters, synthetized by microorganisms under unbalanced growth conditions, making them both bio-based and biodegradable polymers with a thermoplastic behavior. Recently, PHAs were used more intensively in biomedical applications because of their tunable mechanical properties, cytocompatibility, adhesion for cells, and controllable biodegradability. Similarly, the 3D-printing technologies show increasing potential in this particular field of application, due to their advantages in tailor-made design, rapid prototyping, and manufacturing of complex structures. In this review, first, the synthesis and the production of PHAs are described, and different production techniques of medical implants are compared. Then, an overview is given on the most recent and relevant medical applications of PHA for drug delivery, vessel stenting, and tissue engineering. A special focus is reserved for the inno-vations brought by the introduction of additive manufacturing in this field, as compared to the traditional techniques. All of these advances are expected to have important scientific and commer-cial applications in the near future

Emerging Gene-Editing Modalities for Osteoarthritis

Osteoarthritis (OA) is a pathological degenerative condition of the joints that is widely prevalent worldwide, resulting in significant pain, disability, and impaired quality of life. The diverse etiology and pathogenesis of OA can explain the paucity of viable preventive and disease-modifying strategies to counter it. Advances in genome-editing techniques may improve disease-modifying solutions by addressing inherited predisposing risk factors and the activity of inflammatory modulators. Recent progress on technologies such as CRISPR/Cas9 and cell-based genome-editing therapies targeting the genetic and epigenetic alternations in OA offer promising avenues for early diagnosis and the development of personalized therapies. The purpose of this literature review was to concisely summarize the genome-editing options against chronic degenerative joint conditions such as OA with a focus on the more recently emerging modalities, especially CRISPR/Cas9. Future advancements in novel genome-editing therapies may improve the efficacy of such targeted treatments

Osteochondral Tissue Engineering: The Potential of Electrospinning and Additive Manufacturing

The socioeconomic impact of osteochondral (OC) damage has been increasing steadily over time in the global population, and the promise of tissue engineering in generating biomimetic tissues replicating the physiological OC environment and architecture has been falling short of its projected potential. The most recent advances in OC tissue engineering are summarised in this work, with a focus on electrospun and 3D printed biomaterials combined with stem cells and biochemical stimuli, to identify what is causing this pitfall between the bench and the patients' bedside. Even though significant progress has been achieved in electrospinning, 3D-(bio)printing, and induced pluripotent stem cell (iPSC) technologies, it is still challenging to artificially emulate the OC interface and achieve complete regeneration of bone and cartilage tissues. Their intricate architecture and the need for tight spatiotemporal control of cellular and biochemical cues hinder the attainment of long-term functional integration of tissue-engineered constructs. Moreover, this complexity and the high variability in experimental conditions used in different studies undermine the scalability and reproducibility of prospective regenerative medicine solutions. It is clear that further development of standardised, integrative, and economically viable methods regarding scaffold production, cell selection, and additional biochemical and biomechanical stimulation is likely to be the key to accelerate the clinical translation and fill the gap in OC treatment

Recent advances in 3D printing of biomaterials.

3D Printing promises to produce complex biomedical devices according to computer design using patient-specific anatomical data. Since its initial use as pre-surgical visualization models and tooling molds, 3D Printing has slowly evolved to create one-of-a-kind devices, implants, scaffolds for tissue engineering, diagnostic platforms, and drug delivery systems. Fueled by the recent explosion in public interest and access to affordable printers, there is renewed interest to combine stem cells with custom 3D scaffolds for personalized regenerative medicine. Before 3D Printing can be used routinely for the regeneration of complex tissues (e.g. bone, cartilage, muscles, vessels, nerves in the craniomaxillofacial complex), and complex organs with intricate 3D microarchitecture (e.g. liver, lymphoid organs), several technological limitations must be addressed. In this review, the major materials and technology advances within the last five years for each of the common 3D Printing technologies (Three Dimensional Printing, Fused Deposition Modeling, Selective Laser Sintering, Stereolithography, and 3D Plotting/Direct-Write/Bioprinting) are described. Examples are highlighted to illustrate progress of each technology in tissue engineering, and key limitations are identified to motivate future research and advance this fascinating field of advanced manufacturing

Vibrational Spectroscopy for In Vitro Monitoring Stem Cell Differentiation

Stem cell technology has attracted considerable attention over recent decades due to its enormous potential in regenerative medicine and disease therapeutics. Studying the underlying mechanisms of stem cell differentiation and tissue generation is critical, and robust methodologies and different technologies are required. Towards establishing improved understanding and optimised triggering and control of differentiation processes, analytical techniques such as flow cytometry, immunohistochemistry, reverse transcription polymerase chain reaction, RNA in situ hybridisation analysis, and fluorescence-activated cell sorting have contributed much. However, progress in the field remains limited because such techniques provide only limited information, as they are only able to address specific, selected aspects of the process, and/or cannot visualise the process at the subcellular level. Additionally, many current analytical techniques involve the disruption of the investigation process (tissue sectioning, immunostaining) and cannot monitor the cellular differentiation process in situ, in real-time. Vibrational spectroscopy, as a label-free, non-invasive and non-destructive analytical technique, appears to be a promising candidate to potentially overcome many of these limitations as it can provide detailed biochemical fingerprint information for analysis of cells, tissues, and body fluids. The technique has been widely used in disease diagnosis and increasingly in stem cell technology. In this work, the efforts regarding the use of vibrational spectroscopy to identify mechanisms of stem cell differentiation at a single cell and tissue level are summarised. Both infrared absorption and Raman spectroscopic investigations are explored, and the relative merits, and future perspectives of the techniques are discussed

Biomimetic strategies for fracture repair: engineering the cell microenvironment for directed tissue formation

Complications resulting from impaired fracture healing have major clinical implications on fracture management strategies. Novel concepts taken from developmental biology have driven research strategies towards the elaboration of regenerative approaches that can truly harness the complex cellular events involved in tissue formation and repair. Advances in polymer technology and a better understanding of naturally derived scaffolds have given rise to novel biomaterials with an increasing ability to recapitulate native tissue environments. This coupled with advances in the understanding of stem cell biology and technology has opened new avenues for regenerative strategies with true clinical translatability. These advances have provided the impetus to develop alternative approaches to enhance the fracture repair process. We provide an update on these advances, with a focus on the development of novel biomimetic approaches for bone regeneration and their translational potential

Biomimetic gradient scaffolds containing hyaluronic acid and sr/zn folates for osteochondral tissue engineering

Regenerative therapies based on tissue engineering are becoming the most promising alternative for the treatment of osteoarthritis and rheumatoid arthritis. However, regeneration of full-thickness articular osteochondral defects that reproduces the complexity of native cartilage and osteochondral interface still remains challenging. Hence, in this work, we present the fabrication, physic-chemical characterization, and in vitro and in vivo evaluation of biomimetic hierarchical scaffolds that mimic both the spatial organization and composition of cartilage and the osteochondral interface. The scaffold is composed of a composite porous support obtained by cryopolymerization of poly(ethylene glycol) dimethacrylate (PEGDMA) in the presence of biodegradable poly(D,L-lactide-co-glycolide) (PLGA), bioactive tricalcium phosphate β-TCP and the bone promoting strontium folate (SrFO), with a gradient biomimetic photo-polymerized methacrylated hyaluronic acid (HAMA) based hydrogel containing the bioactive zinc folic acid derivative (ZnFO). Microscopical analysis of hierarchical scaffolds showed an open interconnected porous open microstructure and the in vitro behaviour results indicated high swelling capacity with a sustained degradation rate. In vitro release studies during 3 weeks indicated the sustained leaching of bioactive compounds, i.e., Sr, Zn and folic acid, within a biologically active range without negative effects on human osteoblast cells (hOBs) and human articular cartilage cells (hACs) cultures. In vitro co-cultures of hOBs and hACs revealed guided cell colonization and proliferation according to the matrix microstructure and composition. In vivo rabbit-condyle experiments in a critical-sized defect model showed the ability of the biomimetic scaffold to promote the regeneration of cartilage-like tissue over the scaffold and neoformation of osteochondral tissue.This research was funded by Spanish MICINN (MAT201573656-JIN), AEI-MICINN (PID2020- 114086RB-100) and CAM (IND2018/BMD-9485