Engineering Extracellular Communication: Glycan Interfaces, Extracellular Vesicles and Soluble Mediators for Integrative and Regenerative Pharmacology

The secretome is more and more recognized as a dynamic communication system regulating tissue homeostasis, immune responses and regeneration. It comprises two major components: soluble mediators (e.g., growth factors, cytokines and chemokines) and extracellular vesicles (EVs). Both represent complementary and equally important systems of extracellular communication. Increasing evidence indicates that their activities involve coordination through dynamic glycan-dependent interfaces involving glycan-binding proteins, glycan-modifying enzymes and extracellular matrix-associated glycoconjugates. Together, these components regulate molecular recognition, receptor organization, immune signaling, tissue repair and communication across biological barriers, thereby shaping both physiological and pathological microenvironments. Recent advances in glycobiology, glycoengineering, extracellular vesicle engineering, protein engineering and biomaterials have fundamentally expanded our ability to manipulate these extracellular communication systems. Rather than merely characterizing secreted factors, emerging technologies now enable the rational design of extracellular signaling networks for therapeutic benefit. This development creates new opportunities for targeted drug delivery, precision medicine, immunopharmacology and regenerative pharmacology. In this Research Topic, we explore the emerging concept of the engineered secretome, describing the pharmacological modulation of extracellular communication through the coordinated engineering of glycan interfaces, glycan-modifying enzymes, glycan-binding proteins, extracellular vesicles and other secreted bioactive molecules. By bringing together researchers from glycobiology, extracellular vesicle biology, lectin biology, drug delivery, biomaterials, tissue engineering, immunopharmacology and regenerative medicine, we aim to establish a multidisciplinary framework for engineering extracellular communication through both soluble mediators and extracellular glycan-dependent interfaces as a therapeutic strategy. We welcome Original Research, Reviews, Mini Reviews, Perspectives, Methods and Hypothesis articles addressing, but not limited to, glycoengineering and enzymatic glycan remodeling; glycobiology of regenerative and disease-associated microenvironments; glycan-binding proteins including galectins, C-type lectins, siglecs, selectins and engineered lectins; extracellular vesicle biology, glycosylation and engineering; engineered secretomes and cell-free therapeutics; biomaterials and tissue-engineered systems; targeted drug delivery; biological barrier crossing; quantitative interaction technologies; advanced imaging; multi-omics approaches; and translational studies spanning mechanistic discovery, preclinical research and early clinical applications. Instead of focusing on individual molecular components, this Research Topic seeks to promote a conceptual shift towards understanding extracellular communication as an integrated and engineerable therapeutic system. The complexity of the secretome cannot be explained by individual factors or isolated signaling pathways alone. Instead, it emerges from the coordinated interplay of soluble mediators, extracellular vesicles, glycan and extracellular interfaces and their interactions across multiple cell types and tissues. We therefore encourage contributions that bridge traditional disciplinary boundaries and provide systems-level insights into how extracellular communication is organized, regulated and can be engineered for innovative pharmacological applications in tissue regeneration, immune modulation and precision medicine. BackgroundThe secretome comprises two major components: soluble mediators (e.g., growth factors, cytokines and chemokines) and extracellular vesicles (EVs). Both represent complementary and equally important systems of extracellular communication. Increasing evidence indicates that their activities are coordinated through dynamic glycan-dependent interfaces involving glycan-binding proteins, glycan-modifying enzymes and extracellular matrix-associated glycoconjugates. Together, these components regulate molecular recognition, receptor organization, immune signalling, tissue repair and communication across biological barriers, thereby shaping both physiological and pathological microenvironments. Novel advances in glycoengineering technologies, protein engineering and extracellular vesicle engineering now enable the rational manipulation of these extracellular communication networks. This shift transforms the secretome from a passive collection of secreted molecules into a programmable therapeutic system, opening new opportunities for precision pharmacology, targeted drug delivery and regenerative medicine. Bringing these rapidly evolving disciplines together is therefore timely and essential to accelerate the development of next-generation therapeutics.GoalThis Research Topic aims to establish the concept of the engineered secretome as a unifying framework for integrative and regenerative pharmacology. We envision extracellular communication as an engineerable therapeutic target in which glycan interfaces serve as programmable molecular platforms, glycan-modifying enzymes function as molecular writers and editors, lectins decode, organize and bridge glycan-dependent signaling, and extracellular vesicles act as versatile carriers of biological information and therapeutic cargo. We welcome contributions that explore the molecular mechanisms, engineering strategies and translational applications of these interconnected systems. Particular emphasis will be placed on studies demonstrating how glycoengineering, engineered lectins, extracellular vesicle engineering and related technologies can improve targeted drug delivery, immune modulation, tissue regeneration, barrier crossing and precision medicine. By integrating glycobiology, pharmacology, extracellular vesicle research, biomaterials and tissue engineering, this Research Topic seeks to define new therapeutic strategies based on programmable extracellular communication.ScopeWe welcome Original Research, Reviews, Mini Reviews, Perspectives, Methods and Hypothesis articles spanning fundamental, translational and preclinical research. Topics include-Glycoengineering, metabolic glycan engineering and enzymatic glycan remodeling; glycan-modifying enzymes and glycan interfaces in health and disease;-Glycan-binding proteins, including galectins, C-type lectins, siglecs, selectins and engineered lectins-Extracellular vesicle biology, glycosylation and engineering -Secretome engineering and extracellular communication networks-Biomaterials, tissue-engineered systems and targeted drug delivery exploiting glycan-dependent interactions-Pharmacological modulation of biological barriers; and advanced technologies, including multi-omics, quantitative interaction analyses and imaging, to investigate extracellular communication. -Advanced drug delivery using extracellular vesicles and secretome-derived platforms, including the delivery of mRNA, siRNA, miRNA, other nucleic acids, proteins and bioactive molecules.-Secretomes and extracellular vesicles as functional components or building blocks of biomaterials and tissue-engineered systems.We particularly encourage multidisciplinary studies that bridge glycobiology, extracellular vesicle research, immunopharmacology, biomaterials, nanomedicine, drug delivery and regenerative medicine, and translate mechanistic discoveries into innovative therapeutic strategies. Topic editors: Anna-Kristin Ludwig, Ana Santos-Coquillat, Xavier BLANCHET Source: https://www.frontiersin.org/research-topics/84294/engineering-extracellular-communication-glycan-interfaces-extracellular-vesicles-and-soluble-mediators-for-integrative-and-regenerative-pharmacology