Jessup Mark, Iglesias Nicholas J, Tadisina Kashyap K, Xu Kyle, Mella-Catinchi Juan, Pinchuk Leonard, Singh Devinder, Tse David T, Nayak Vasudev Vivekanand, Coelho Paulo G
University of Miami Miller School of Medicine, Miami, FL 33136, USA.
DeWitt Daughtry Family Department of Surgery, University of Miami Miller School of Medicine, Miami, FL 33136, USA.
Biomater Biosyst. 2025 Aug 9;19:100117. doi: 10.1016/j.bbiosy.2025.100117. eCollection 2025 Sep.
The cerebral lymphatic system plays a critical role in central nervous system (CNS) homeostasis through fluid regulation, toxin clearance, and immune modulation. Recent discoveries in the glial-lymphatic (glymphatic) and meningeal lymphatic systems have demonstrated their involvement in a spectrum of CNS pathologies such as Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), multiple sclerosis (MS), traumatic brain injury (TBI), stroke, and cancers. This review summarizes current understanding of the cerebral lymphatic system's mechanisms and their contribution to CNS health. Furthermore, we emphasize the linkage of lymphatic dysfunction and the pathogenesis of neurodegenerative and neuroinflammatory etiologies. Lymphatic alterations such as deep cervical lymph node (DCLN) manipulation have been shown to increase function, reduce toxin accumulation and improve disease. Other techniques like supermicrosurgical interventions of lymphaticovenular (lymphovenous) anastomosis and lymphatic reconstruction have recently demonstrated therapeutic benefits. Novel approaches of supermicrosurgical techniques, such as cervical shunting to decompress lymphatic systems (CSULS), have displayed promising cognitive improvements in AD patients. We additionally explore the role of biomaterials in improving interventional outcomes and their potential to be applied to lymphatic surgical developments. Despite their widespread applications in surgical practice, the use of biomaterials in cerebral lymphatic reconstruction remains unexplored. This review discusses the potential benefits of integrating biomaterials into emerging lymphatic interventions to improve patient outcomes.
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