Exosomes, a subset of extracellular vesicles, have emerged as potential therapeutic agents in ophthalmology due to their ability to modulate immune responses, facilitate cellular communication, and promote tissue repair. This chapter explores the potential applications of exosome-based therapies in corneal and anterior segment disorders, retinal diseases, glaucoma, and Sjögren's syndrome. In corneal disorders, mesenchymal stem cell (MSC)-derived secretomes have shown promise in accelerating wound healing, reducing fibrosis, and modulating inflammation, with hydrogel encapsulation strategies potentially enhancing their efficacy. In retinal diseases, exosomes may provide neuroprotective effects in age-related macular degeneration, diabetic retinopathy, and retinitis pigmentosa by modulating oxidative stress and inflammation. In glaucoma, secretome-based therapies could support retinal ganglion cell survival and optic nerve regeneration, though their impact on intraocular pressure via the trabecular meshwork remains uncertain. Additionally, exosomal biomarkers in aqueous humor are being investigated as potential diagnostic tools. In Sjögren's syndrome, exosomal biomarkers may facilitate earlier detection, while stem cell-derived exosomes hold promise in modulating immune responses and restoring glandular function. Despite encouraging preclinical and early clinical findings, standardization, scalability, and long-term safety must be addressed before clinical translation. Future research will focus on optimizing exosome-based therapies and exploring their feasibility for ophthalmic applications.

Upon inflammation, the bone marrow (BM) landscape undergoes significant architectural and functional modifications. Stimulation of the hematopoietic niche triggers a series of lightning events, which begin with stem/progenitor blood elements mobilization and culminates with the activation of immune responses. Ageing partially mirrors this process, albeit with a propensity towards chronic inflammation and immune dysfunction. Age-related chronic inflammation disrupts bone homeostasis and accompanies impaired tissue regeneration. Thus, focusing on the bone marrow's dynamics during inflammatory bone diseases could lay the way for the development of novel therapeutic platforms aimed at niche reprogramming. Herein, we summarize inflammatory and age-induced processes in multiple BM compartments, with particular reference to hematopoietic, stromal stem/progenitor cells, and mature immunocytes. Finally, we focus on autophagy and its potential to clinically re-modulate the pathological "flogistic" bias, possibly by restoring functional phenotypes within the bone marrow niche elements.

Despite advances in cancer research, treating malignancies remains challenging due to issues like drug resistance, disease heterogeneity, and the limited efficacy of current therapies, particularly in relapsed or refractory cases. In recent years, several drugs originally approved for non-cancer indications have shown potential in cancer treatment, demonstrating anti-proliferative, anti-metastatic, and immunomodulatory effects. Drug repurposing has shown immense promise due to well-established safety profiles and mechanisms of action of the compounds. However, the implementation is fraught with clinical, logistical, regulatory, and ethical challenges, especially in diseases such as leukaemia and multiple myeloma. This chapter examines the treatment challenges in leukaemia and multiple myeloma, focusing on the role of drug repurposing in addressing therapeutic resistance and disease variability. It highlights the potential of personalized, tailored combination therapies, using repurposed drug components, to offer more effective, targeted, and cost-efficient treatment strategies, overcoming resistance and improving patient outcomes.

Bone marrow transplantation is considered a cornerstone in the treatment of hematologic malignancies and blood disorders. While it may offer the possibility of a cure through the use of high-dose chemotherapy and radiation, outcomes are significantly impacted by biological and medical factors. Herein, aging is associated with reduced hematopoiesis, immune function, and overall regenerative capacity of tissues. Growth arrest, a crucial property of cellular senescence, inhibits bone marrow function, lowers immune surveillance in aged adults, and reduces the efficiency of bone marrow transplantation. The clinical course for older recipients is further complicated by the presence of prolonged immunosuppression, slower recovery, and higher complication rates, including life-threatening graft-versus-host disease. Accordingly, there is increasing interest in explaining how aging, cellular senescence, and transplant outcomes are interrelated. The current chapter outlines the mechanisms whereby aging and senescence contribute to the immunological dysregulation and poor bone marrow transplantation outcomes observed in elderly cancer patients. The authors' goal is to suggest therapeutic approaches that will enhance the quality of life and survival rates of elderly bone marrow transplant recipients.

Mitochondria play a critical role in cellular communication, cell proliferation, and apoptosis, which make them essential to maintaining cellular health. Recently, mitochondrial transplantation has emerged as a promising therapeutic approach to treat conditions such as ischemia, neurodegenerative diseases, and cardiovascular disorders by restoring mitochondrial function in damaged cells. Despite its potential, understanding mitochondrial behavior in vivo remains challenging; however, organoid models, which are three-dimensional structures derived from stem cells that mimic human tissues, offer a solution to study mitochondrial function and transplantation strategies under controlled conditions. These models are particularly necessary in studies, as they can replicate disease conditions and consequently enable researchers to investigate mitochondrial dynamics and therapeutic integration. Developing organoid systems optimized for mitochondrial transplantation requires exploring factors that influence mitochondrial uptake, refining transplantation strategies, and understanding their role in cellular regeneration in order to advance in the field of mitochondrial research.

Advances in regenerative medicine, cell therapy, and 3D bioprinting are reshaping the landscape of ocular surgery, offering innovative approaches to address complex conditions affecting the cornea, ocular adnexal structures, and the orbit. These technologies hold the potential to enhance treatment precision, improve functional outcomes, and address limitations in traditional surgical and therapeutic interventions.The cornea, as the eye's primary refractive and protective barrier, is particularly well-suited for regenerative approaches due to its avascular and immune-privileged nature. Cell-based therapies, including limbal stem cell transplantation as well as stromal keratocyte and corneal endothelial cell regeneration, are being investigated for their potential to restore corneal clarity and function in conditions such as limbal stem cell deficiency, keratoconus, and endothelial dysfunction. Simultaneously, 3D bioprinting technologies are enabling the development of biomimetic corneal constructs, potentially addressing the global shortage of donor tissues and facilitating personalized surgical solutions.In oculoplastic and orbital surgery, regenerative strategies and cell therapies are emerging as possible alternatives to conventional approaches for conditions such as eyelid defects, meibomian gland dysfunction, and Graves' orbitopathy. Stem cell-based therapies and bioengineered scaffolds are showing potential in restoring lacrimal glands' function as well as reconstructing complex ocular adnexal and orbital structures. Moreover, 3D-printed orbital implants and scaffolds offer innovative solutions for repairing traumatic, post-tumor resection, and congenital defects, with the potential for improved biocompatibility and precision.Molecular and gene-based therapies, including exosome delivery systems, nanoparticle-based interventions, and gene-editing techniques, are expanding the therapeutic arsenal for ophthalmic disorders. These approaches aim to enhance the efficacy of regenerative treatments by addressing underlying pathophysiological mechanisms of diseases. This chapter provides an overview of these advancements and the challenges of translating laboratory discoveries into effective therapies in clinical practice.

Neuroregeneration refers to the ability of the nervous system to repair or regenerate neural components subsequently to spinal cord and traumatic brain injuries, peripheral nerve damage, and neurodegenerative diseases. Here, we discuss lead effectors of the healing process, neural stem cells, and non-invasive physical methods, for neuroregeneration de novo and in situ.

Three-dimensional (3D) disease modeling and drug screening systems have become important in tissue engineering, drug screening, and development. The newly developed systems support cell and extracellular matrix (ECM) interactions, which are necessary for the formation of the tissue or an accurate model of a disease. Hydrogels are favorable biomaterials due to their properties: biocompatibility, high swelling capacity, tunable viscosity, mechanical properties, and their ability to biomimic the structure and function of ECM. They have been used to model various diseases such as tumors, cancer diseases, neurodegenerative diseases, cardiac diseases, and cardiovascular diseases. Additive manufacturing approaches, such as 3D printing/bioprinting, stereolithography (SLA), selective laser sintering (SLS), and fused deposition modeling (FDM), enable the design of scaffolds with high precision; thus, increasing the accuracy of the disease models. In addition, the aforementioned methodologies improve the design of the hydrogel-based scaffolds, which resemble the complicated structure and intricate microenvironment of tissues or tumors, further advancing the development of therapeutic agents and strategies. Thus, 3D hydrogel-based disease models fabricated through additive manufacturing approaches provide an enhanced 3D microenvironment that empowers personalized medicine toward targeted therapeutics, in accordance with 3D drug screening platforms.

Compartmentalization in eukaryotic cells allows the spatiotemporal regulation of biochemical processes, in addition to allowing specific sets of proteins to interact in a regulated as well as stochastic manner. Although membrane-bound organelles are thought to be the key players of cellular compartmentalization, membraneless biomolecular condensates such as stress granules, P bodies, and many others have recently emerged as key players that are also thought to bring order to a highly chaotic environment. Here, we have evaluated the latest studies on biomolecular condensates, specifically focusing on how they interact with membrane-bound organelles and modulate each other's functions. We also highlight the importance of this interaction in neurodegenerative and cardiovascular diseases as well as in cancer.

Despite advances in healthcare, bacterial pathogens remain a severe global health threat, exacerbated by rising antibiotic resistance. Lower respiratory tract infections, with their high death toll, are of particular concern. Accurately replicating host-pathogen interactions in laboratory models is crucial for understanding these diseases and evaluating new therapies. In this communication, we briefly present existing in vivo models for cystic fibrosis and their limitations in replicating human respiratory infections. We then present a novel, 3D-printed, cytocompatible microfluidic lung-on-a-chip device, designed to simulate the human lung environment, and with possible use in recapitulating general infectious diseases.Our device enables the colonisation of fully differentiated lung epithelia at an air-liquid interface with Pseudomonas aeruginosa, a key pathogen in many severe infections. By incorporating dynamic flow, we replicate the clearance of bacterial toxins and planktonic cells, simulating both acute and chronic infections. This platform supports real-time monitoring of therapeutic interventions, mimics repeated drug administrations as in clinical settings, and facilitates the analysis of colony-forming units and cytokine secretion over time. Our findings indicate that this lung-on-a-chip device has significant potential for advancing infectious disease research, in optimizing treatment strategies against infections and in developing novel treatments.