Extracellular vesicles have emerged as promising tools in regenerative medicine due to their inherent ability to facilitate intercellular communication and modulate cellular functions. These nanosized vesicles transport bioactive molecules, such as proteins, lipids, and nucleic acids, which can affect the behavior of recipient cells and promote tissue regeneration. However, the therapeutic application of these vesicles is frequently constrained by their rapid clearance from the body and inability to maintain a sustained presence at the injury site. In order to overcome these obstacles, hydrogels have been used as extracellular vesicle delivery vehicles, providing a localized and controlled release system that improves their therapeutic efficacy. This Review will examine the role of extracellular vesicle-loaded hydrogels in tissue regeneration, discussing potential applications, current challenges, and future directions. We will investigate the origins, composition, and characterization techniques of extracellular vesicles, focusing on recent advances in exosome profiling and the role of machine learning in this field. In addition, we will investigate the properties of hydrogels that make them ideal extracellular vesicle carriers. Recent studies utilizing this combination for tissue regeneration will be highlighted, providing a comprehensive overview of the current research landscape and potential future directions.

Background: Ineffective integration has been recognized as one of the major causes of early orthopedic failure of titanium-based implants. One strategy to address this problem is to develop modified titanium surfaces that promote osteoblast differentiation. This study explored titanium surfaces modified with TiO2 nanotubes (TiO2 NTs) capable of localized drug delivery into bone and enhanced osteoblast cell differentiation. Materials and Methods: Briefly, TiO2 NTs were subjected to anodic oxidation and loaded with Metformin, a widely used diabetes drug. To create surfaces with sustainable drug-eluting characteristics, TiO2 NTs were spin coated with a thin layer of chitosan. The surfaces were characterized via scanning electron microscopy, atomic force microscopy, and contact angle measurements. The surfaces were then exposed to mesenchymal bone marrow stem cells (MSCs) to evaluate cell adhesion, growth, differentiation, and morphology on the modified surfaces. Results: A noticeable increase in drug release time (3 days vs 20 days) and a decrease in burst release characteristics (85% to 7%) was observed in coated samples as compared to uncoated samples, respectively. Chitosan-coated TiO2 NTs exhibited a considerable enhancement in cell adhesion, proliferation, and genetic expression of type I collagen, and alkaline phosphatase activity as compared to uncoated TiO2 NTs. Conclusion: TiO2 NT surfaces with a chitosan coating are capable of delivering Metformin to a bone site over a sustained period of time with the potential to enhance MSCs cell attachment, proliferation, and differentiation.

Regenerating skin tissue remains a major challenge in medical science, especially due to the risk of scarring and prolonged healing, which becomes even more complicated in people with diabetes. Recent advancements have led to the creation of therapeutic dressings incorporating drug‐delivery systems to tackle these issues. Exosomes (Exos) derived from mesenchymal stem cells (MSCs) have gained significant attention for mediating therapy without directly using cells, thanks to their natural anti‐inflammatory and tissue repair properties mirroring those of MSCs. In this study, an advanced wound dressing combines chitosan (CS) and polyethylene glycol (PEG) hydrogel with adipose MSCs‐derived Exos (ADMSCs‐Exos). This composite, formed using a straightforward blending technique, is engineered to improve the healing process of severe skin injuries by steadily releasing Exos as the hydrogel degrades. The in vitro studies demonstrate that this hydrogel‐exosome dressing greatly enhances endothelial cell migration, reduces oxidative stress, and promotes angiogenesis, crucial for effective wound healing. Additionally, real time‐polymerase chain reaction (RT‐PCR) analysis revealed significant upregulation of key genes involved in these processes, supporting the therapeutic potential of the hydrogel‐Exo combination. These findings emphasize the potential of this hydrogel‐Exos combination as an innovative and promising solution for advanced wound care.

Myocardial infarction (MI) often results in significant damage to heart tissues, leading to cardiac dysfunction, fibrosis, and diminished cell–cell communication.

In the field of orthopedic surgery, large bone defects resulting from trauma, surgical resection, or congenital anomalies present significant challenges. In many cases, treatment necessitates scaffold structures that not only support bone regeneration but also address potential bacterial infections that can impede healing. In this study, we developed 3D bioprinted scaffolds using hydrogel‐based biomaterial ink comprising a blend of chitosan (CS) and agarose (AG), each separately fortified with ZnO, MgO, and CaO nanoparticles (NPs). We performed a comprehensive assessment of the inks' printability and wettability, and ascertained their rheological properties. The in vitro degradation of 3D bioprinted scaffolds was analyzed, their antibacterial capabilities against Escherichia coli ( E. coli ) and Staphylococcus aureus ( S. aureus ) were explored, and the differentiation of bone marrow mesenchymal stem cells (BMSCs) was evaluated. The findings indicated that the hydrogel, CS‐AG (CA), composed of 3.5% (w/v) CS and 1.5% (w/v) AG, demonstrated superior printing characteristics. Among the nanoparticles, ZnO proved to be a notable booster of antibacterial activity and facilitated osteogenic differentiation and proliferation of bone marrow stem cells. Conversely, MgO showed similar antibacterial efficacy but was less successful in promoting cell proliferation compared to ZnO and CaO, whereas CaO displayed the weakest antibacterial efficacy. The results identify the ZnO NP‐loaded CA biomaterial ink as a viable option for addressing bone abnormalities, enhancing bone repair, and preventing bacterial infection.

Effective wound healing requires scaffolds that can prevent infection and support tissue regeneration. Bioprinted chitosan hydrogels are promising candidates due to their biocompatibility, biodegradability, and tunable properties. To further enhance their functionality, we employed two plasma processing strategies using cold atmospheric pressure plasma jets. The plasma treatment of the chitosan solvent used to prepare the hydrogel markedly enhanced the mechanical strength, thermal stability, and antibacterial characteristics (≥2‐log reduction) of the bioprinted scaffolds, rendering them suitable for applications requiring long‐term durability and infection resistance. The plasma treatment of the already printed scaffolds improved surface bioactivity, facilitating enhanced cell adhesion and proliferation, which are essential for tissue regeneration.