Bone fracture healing is a challenging process, due to insufficient and slow tissue repair. Sufferers from bone fractures struggle with one-third of nonunion, display graft rejection, high-costed implantation, or chronic pain. Novel advances in tissue engineering presented promising options for this strain. Biomaterials for bone repair allow accelerated regeneration, osteoblastic cell activation, and enhanced bone remodeling. There is a wide range of biomaterials that are biocompatible, bioresorbable, and biodegradable and used for bone tissue regeneration, promoting osteoconductive and osteoinductive properties. The main aim of bone tissue engineering is to generate rapid and optimal functional bone regeneration through a combination of biomaterials, growth factors, cells, and various agents. Recently bone tissue engineering has been attracted to the use of bioactive glass scaffolds incorporated with polymers and patient-specific fabrication of the bone healing material by 3D bioprinting. There are promising future outcomes that were reported by several research. The present review provides an outlook for recent most common biomaterials in bone tissue engineering suggesting bone tissue engineering practices should have been proceeded to clinical application.

Hücre Fizyolojisi Damla AYKORA Kan Fizyolojisi Ferhat ŞİRİNYILDIZ Kas Fizyolojisi Özlem BARUTÇU Kardiyovasküler Sistem Fizyolojisi Seda UĞRAŞ HARMAN Solunum Sistemi Fizyolojisi Mehmet ÖZ Boşaltım Sistemi Fizyolojisi Seda UĞRAŞ HARMAN Endokrin Sistem Fizyolojisi Ferhat ŞİRİNYILDIZ Üreme Sistemi Fizyolojisi Burcu KÖKSAL Sindirim Sistemi Fizyolojisi İlknur BİRSEN Duyu Fizyolojisi Elif Ezgi GÜREL Sinir Sistemi Fizyolojisi Gül Şahika GÖKDEMİR

Introduction: Plant-derived Exosome-like Nanovesicles (PELNs) have the potential to exhibit improved biological functions in multiple pathological disorders, particularly in neurodegenerative and age-related brain diseases. In this review, advanced isolation techniques, including Differential Ultracentrifugation (dUC), Size-Exclusion Chromatography (SEC), and Polyethylene Glycol (PEG) precipitation, were systematically evaluated to optimize the structural integrity, purity, and biological activity of PELNs. Methods: Novel studies on PELNs were the primary focus of this review. Evidence-based studies were compared and discussed in terms of chemical and functional characteristics, as well as optimized production strategies to enhance the therapeutic properties of PELNs. Results: According to the consensus of reviewed studies, PELNs demonstrate efficient cellular uptake due to their lipophilic chemical structures and modulate intracellular signaling pathways related to neurodegeneration. The main drawbacks of PELNs' utilization mostly depend on the extraction methods and limited delivery through the BBB. A combination of optimized methods, such as dUC and SEC, may exhibit maintained therapeutic strategies for neurological applications. Discussion: Due to the limited number of experimental studies in Parkinson’s Disease (PD) and Alzheimer’s Disease (AD), and brain aging, advances in PELNs extraction methods have been shown to enhance BBB delivery and therapeutic efficacy. Every study claims the superiority of its own method; however, none of these methods fully addresses the limitations inherent in producing optimal results. Conclusion: PELNs represent a promising platform for neurological dysfunction and brain aging-related disorders. However, isolation and characterization methods must be carefully optimized and validated to ensure the production of therapeutically active PELNs suitable for BBB delivery.