Harnessing Immunomodulatory Polymers for Treatment of Autoimmunity, Allergy, and Transplant Rejection.

Autoimmunity, allergy, and transplant rejection are a collection of chronic diseases that are currently incurable, drastically decrease patient quality of life, and consume considerable health care resources. Underlying each of these diseases is a dysregulated immune system that results in the mounting of an inflammatory response against self or an innocuous antigen. As a consequence, afflicted patients are required to adhere to lifelong regimens of multiple immunomodulatory drugs to control disease and reclaim agency. Unfortunately, current immunomodulatory drugs are associated with a myriad of side effects and adverse events, such as increased risk of cancer and increased risk of serious infection, which negatively impacts patient adherence rates and quality of life. The field of immunoengineering is a new discipline that aims to harness endogenous biological pathways to thwart disease and minimize side effects using novel biomaterial-based strategies. We highlight and discuss polymeric micro/nanoparticles with inherent immunomodulatory properties that are currently under investigation in biomaterial-based therapies for treatment of autoimmunity, allergy, and transplant rejection.

Oral Administration of Limosilactobacillus reuteri KBL346 Ameliorates Influenza Virus A/PR8 Infection in Mouse.

Influenza virus infection is an important public-health concern because of its high transmissibility and potential for severe complications. To mitigate the severity and complications of influenza, probiotics containing Lactobacillus are used and generally recognized as safe. We evaluated the anti-influenza effect of Limosilactobacillus reuteri (L. reuteri) KBL346, isolated from the fecel sample of healthy South Koreans, in mice. BALB/c mice were orally administered live and heat-inactivated L. reuteri KBL346. After infection with influenza virus (A/Puerto Rico/8/34) 0.5 times the 50% lethal dose (LD50), body weight loss was improved and recovery was accelerated. Furthermore, L. reuteri KBL346 improved body weight loss and survival rate of mice infected with 4 times the LD50 of influenza virus. Heat-inactivated L. reuteri KBL346 reduced the viral titer in the lung and the plasma immunoglobulin G level. Expression levels of genes encoding inflammatory cytokines, such as interferon-γ and toll-like receptor 2 (Tlr2), were decreased in the lung tissues of mice administered L. reuteri KBL346. Live and heat-inactivated L. reuteri KBL346 increased the expression level of Adamts4, which promotes recovery after infection, and decreased that of Tlr2. The α-diversity of the gut microbiome was modulated by the administration of L. reuteri KBL346. In addition, the structure of the gut microbial community differed according to the degree of weight loss. L. reuteri KBL346 has the potential to alleviate disease severity and improve histopathological changes in mice infected with influenza A/PR8, suggesting its efficacy as a probiotic against influenza infection.

An injectable magnesium-loaded hydrogel releases hydrogen to promote osteoporotic bone repair via ROS scavenging and immunomodulation.

Background: The repair of osteoporotic bone defects remains challenging due to excessive reactive oxygen species (ROS), persistent inflammation, and an imbalance between osteogenesis and osteoclastogenesis. Methods: Here, an injectable H2-releasing hydrogel (magnesium@polyethylene glycol-poly(lactic-co-glycolic acid), Mg@PEG-PLGA) was developed to remodel the challenging bone environment and accelerate the repair of osteoporotic bone defects. Results: This Mg@PEG-PLGA gel shows excellent injectability, shape adaptability, and phase-transition ability, can fill irregular bone defect areas via minimally invasive injection, and can transform into a porous scaffold in situ to provide mechanical support. With the appropriate release of H2 and magnesium ions, the 2Mg@PEG-PLGA gel (loaded with 2 mg of Mg) displayed significant immunomodulatory effects through reducing intracellular ROS, guiding macrophage polarization toward the M2 phenotype, and inhibiting the IκB/NF-κB signaling pathway. Moreover, in vitro experiments showed that the 2Mg@PEG-PLGA gel inhibited osteoclastogenesis while promoting osteogenesis. Most notably, in animal experiments, the 2Mg@PEG-PLGA gel significantly promoted the repair of osteoporotic bone defects in vivo by scavenging ROS and inhibiting inflammation and osteoclastogenesis. Conclusions: Overall, our study provides critical insight into the design and development of H2-releasing magnesium-based hydrogels as potential implants for repairing osteoporotic bone defects.

Indigo Naturalis in Inflammatory Bowel Disease: mechanisms of action and insights from clinical trials.

This study investigates the therapeutic potential of Indigo Naturalis (IN) in treating a Inflammatory Bowel Disease (IBD). The objective is to comprehensively examine the effects and pharmacological mechanisms of IN on IBD, assessing its potential as an novel treatment for IBD. Analysis of 11 selected papers is conducted to understand the effects of IN, focusing on compounds like indirubin, isatin, indigo, and tryptanthrin. This study evaluates their impact on Disease Activity Index (DAI) score, colon length, mucosal damage, and macrophage infiltration in Dextran Sulfate Sodium (DSS)-induced colitis mice. Additionally, It investigate into the anti-inflammatory mechanisms, including Aryl hydrocarbon Receptor (AhR) pathway activation, Nuclear Factor kappa B (NF-κB)/nod-like receptor family pyrin domain containing 3 (NLRP3)/Interleukin 1 beta (IL-1ß) inhibition, and modulation of Toll-like receptor 4 (TLR4)/myeloid differentiation primary response 88 (MYD88)/NF-κB and Mitogen Activated Protein Kinase (MAPK) pathways. Immunomodulatory effects on T helper 17 (Th17)/regulatory T cell (Treg cell) balance and Glycogen synthase kinase-3 beta (GSK3-ß) expression are also explored. Furthermore, the study addresses the role of IN in restoring intestinal microbiota diversity, reducing pathogenic bacteria, and increasing beneficial bacteria. The findings reveal that IN, particularly indirubin and indigo, demonstrates significant improvements in DAI score, colon length, mucosal damage, and macrophage infiltration in DSS-induced colitis mice. The anti-inflammatory effects are attributed to the activation of the AhR pathway, inhibition of inflammatory pathways, and modulation of immune responses. These results exhibit the potential of IN in IBD treatment. Notably, the restoration of intestinal microbiota diversity and balance further supports its efficacy. IN emerges as a promising and effective treatment for IBD, demonstrating anti-inflammatory effects and positive outcomes in preclinical studies. However, potential side effects necessitate further investigation for safe therapeutic development. The study underscores the need for future research to explore a broader range of active ingredients in IN to enhance therapeutic efficacy and safety.

Harnessing immunity: Immunomodulatory therapies in COVID-19.

An overly exuberant immune response, characterized by a cytokine storm and uncontrolled inflammation, has been identified as a significant driver of severe coronavirus disease 2019 (COVID-19) cases. Consequently, deciphering the intricacies of immune dysregulation in COVID-19 is imperative to identify specific targets for intervention and modulation. With these delicate dynamics in mind, immunomodulatory therapies have emerged as a promising avenue for mitigating the challenges posed by COVID-19. Precision in manipulating immune pathways presents an opportunity to alter the host response, optimizing antiviral defenses while curbing deleterious inflammation. This review article comprehensively analyzes immunomodulatory interventions in managing COVID-19. We explore diverse approaches to mitigating the hyperactive immune response and its impact, from corticosteroids and non-steroidal drugs to targeted biologics, including anti-viral drugs, cytokine inhibitors, JAK inhibitors, convalescent plasma, monoclonal antibodies (mAbs) to severe acute respiratory syndrome coronavirus 2, cell-based therapies (i.e., CAR T, etc.). By summarizing the current evidence, we aim to provide a clear roadmap for clinicians and researchers navigating the complex landscape of immunomodulation in COVID-19 treatment.

Clinical outcomes of flavonoids for immunomodulation in inflammatory bowel disease: a narrative review.

Inflammatory bowel disease is a debilitating condition that undergoes a relapsing and remitting course. The pathogenesis of how this disease manifests remains to be elucidated; however, there is growing evidence that a synergism of familial predisposition and epigenetic alterations influenced by environmental factors all contribute to the development of the disease. The role of nutrition in improving the outcomes of the condition has garnered increasing interest, given the greater risks of neoplastic conversion and concerns about inappropriate remission with available pharmacotherapeutic treatments alone. Available reports, often anecdotal, have documented patient relief with employment of various dietary strategies. These have led to curiosity about nutritional assessments and nutrition therapies to ameliorate the morbidity and all-cause mortality of the disease. One group of such nutrition therapies, supported by a compendium of available articles, is flavonoids-although the greater abundance of in vitro experiments with relatively few clinical trials has limited their clinical use. Nonetheless, flavonoids have been shown to be functional foods with immunomodulatory capabilities. This article will thus delve into the role of flavonoids in altering the course of the immune response in inflammatory bowel disease, while assessing their clinical outcomes in human trials.

Exploring the Potential of Glycolytic Modulation in Myeloid-Derived Suppressor Cells for Immunotherapy and Disease Management.

Recent advancements in various technologies have shed light on the critical role of metabolism in immune cells, paving the way for innovative disease treatment strategies through immunometabolism modulation. This review emphasizes the glucose metabolism of myeloid-derived suppressor cells (MDSCs), an emerging pivotal immunosuppressive factor especially within the tumor microenvironment. MDSCs, an immature and heterogeneous myeloid cell population, act as a double-edged sword by exacerbating tumors or mitigating inflammatory diseases through their immune-suppressive functions. Numerous recent studies have centered on glycolysis of MDSC, investigating the regulation of altered glycolytic pathways to manage diseases. However, the specific changes in MDSC glycolysis and their exact functions continue to be areas of ongoing discussion yet. In this paper, we review a range of current findings, including the latest research on the alteration of glycolysis in MDSCs, the consequential functional alterations in these cells, and the outcomes of attempts to modulate MDSC functions by regulating glycolysis. Ultimately, we will provide insights into whether these research efforts could be translated into clinical applications.

Immune mechanisms and predictive biomarkers related to neoadjuvant immunotherapy response in stage III melanoma.

The treatment for stage III melanoma has advanced significantly, nevertheless, a substantial proportion of patients experience relapse. Neoadjuvant immune checkpoint blockade has emerged as a promising approach, allowing early micrometastatic disease treatment, reduction of tumor burden before surgery, and enhanced tumor-specific T-cell responses. However, not all patients respond to treatment, highlighting the need for understanding immune mechanisms behind failure and identification of predictive markers. Here we performed a robust evaluation of systemic and tumoral immune profiles in a well-defined cohort of advanced melanoma patients treated with immune checkpoint inhibitors. Elevated CTACK and CXCL9 chemokines pre-treatment suggested their potential as predictive tools for treatment response. Furthermore, CD95 expression in CD8+ T lymphocytes surfaced as a favorable prognostic indicator, while PD-1, CD161, and PD-L2 exhibited correlations with worst outcomes. These findings shed light on the intricate interplay between immune markers and melanoma response to neoadjuvant immune checkpoint therapy, offering insights into personalized treatment strategies.

Nanobody Mediated Atrazine Resistance in Plants.

In planta expression of recombinant antibodies has been proposed as a strategy for herbicide resistance but is not well advanced yet. Here, an atrazine nanobody gene fused with a green fluorescent protein tag was transformed to Arabidopsis thaliana, which was confirmed with PCR, ELISA, and immunoblotting. High levels of nanobody accumulation were observed in the nucleus, cytoderm, and cytosol. The nanobody expressed in the plant had similar affinity, sensitivity, and selectivity as that expressed in Escherichia coli. The T3 homozygous line showed resistance in a dose-dependent manner up to 380 g ai/ha of atrazine, which is approximately one-third of the recommended field application rate. This is the first report of utilizing a nanobody in plants against herbicides. The results suggest that utilizing a high-affinity herbicide nanobody gene rather than increasing the expression of nanobodies in plants may be a technically viable approach to acquire commercial herbicide-resistant crops and could be a useful tool to study plant physiology.

Schisandrin A can promote the anti-tumor effect of 5-Fu by reversing the immunosuppressive state of the body in rat.

In this study, based on Walker 256 in vitro experiments, CCK-8 assay, clone formation assay, wound healing assay, and flow cytometry were used to detect cell apoptosis and cell cycle. It was found that schisandrin may have significant anti-tumor effects in vitro by inhibiting TGF-ß/Smad signaling pathway. In addition, in vivo experiments, immunohistochemistry was used to observe the expression of HIF-1α, VEGF and VEGFR-2 in tumor tissues. It was found that schisandrin could significantly improve the immunosuppression induced by 5-Fu and enhance the antitumor effect of 5-Fu. The mechanism may be related to the inhibition of Wnt-1/ß-catenin signaling pathway.

Navigating the Modern Landscape of Sepsis: Advances in Diagnosis and Treatment.

Sepsis poses a significant threat to human health due to its high morbidity and mortality rates worldwide. Traditional diagnostic methods for identifying sepsis or its causative organisms are time-consuming and contribute to a high mortality rate. Biomarkers have been developed to overcome these limitations and are currently used for sepsis diagnosis, prognosis prediction, and treatment response assessment. Over the past few decades, more than 250 biomarkers have been identified, a few of which have been used in clinical decision-making. Consistent with the limitations of diagnosing sepsis, there is currently no specific treatment for sepsis. Currently, the general treatment for sepsis is conservative and includes timely antibiotic use and hemodynamic support. When planning sepsis-specific treatment, it is important to select the most suitable patient, considering the heterogeneous nature of sepsis. This comprehensive review summarizes current and evolving biomarkers and therapeutic approaches for sepsis.

The Cytokine Levels of Cord Blood- and Wharton's Jelly-Derived Mesenchymal Stem Cells from Early to Late Passages.

Mesenchymal stem cells (MSCs) are promising for clinical studies owing to their self-renewal, multipotency, trophic, and immunomodulatory properties. This study aimed to investigate the cytokine levels of human umbilical cord blood (CB) and Wharton's Jelly-(WJ) derived MSCs relevant to immune modulation on different passage levels in vitro. Umbilical CB MSCs were isolated using the ficoll-paque gradient method, and WJ-MSCs were isolated by the explant method. After isolation, the MSCs were characterized using flow cytometry. The supernatant cytokine levels (interferon-gamma (IFN-γ), interleukin 4 (IL-4), interleukin 17 (IL-17)) of MSCs at each passage were evaluated using the ELISA assay. MSCs exhibited different cytokine levels with each passage number. In WJ-MSC culture supernatants, IL-17 levels significantly increased at P4 and P5 compared to the first passage (p < 0.005), while the other passages showed a decrease. IFN-γ levels increased at passage P1 and P4 and decreased at other passages (p < 0.005). IL-4 levels significantly increased only at passage P3 (p < 0.005). In CB-MSC culture supernatants, IL-17 and IL-4 cytokines decreased compared to P0, while IFN-γ cytokine increased from P0 (p < 0.005). The changing ratio of cytokine levelsfor both CB-MSCs and WJ-MSCs were similarly maintained from early to late passages. More research is needed to understand the immunomodulatory functions of MSCs.

Association Between Gut and Nasal Microbiota and Allergic Rhinitis: A Systematic Review.

Allergic rhinitis is a chronic non-infectious inflammation of the nasal mucosa mediated by specific IgE. Recently, the human microbiome has drawn broad interest as a potential new target for treating this condition. This paper succinctly summarizes the main findings of 17 eligible studies published by February 2024, involving 1044 allergic rhinitis patients and 954 healthy controls from 5 countries. These studies examine differences in the human microbiome across important mucosal interfaces, including the nasal and intestinal areas, between patients and controls. Overall, findings suggest variations in the gut microbiota between allergic rhinitis patients and healthy individuals, although the specific bacterial taxa that significantly changed were not always consistent across studies. Due to the limited scope of existing research and patient coverage, the relationship between the nasal microbiome and allergic rhinitis remains inconclusive. The article discusses the potential immune-regulating role of the gut microbiome in allergic rhinitis. Further well-designed clinical trials with large-scale recruitment of allergic rhinitis patients are encouraged.

Unraveling colorectal cancer prevention: The vitamin D - gut flora - immune system nexus.

Colorectal cancer (CRC) is one of the most common cancers diagnosed in the world. Although environmental and genetic factors play a major role in the pathogenesis of CRC, extensive research has suggested that vitamin D may play a pivotal role in the development of CRC. Vitamin D, primarily obtained through sunlight exposure, dietary sources, and supplements, has long been recognized for its essential functions in maintaining health, including immune regulation. This article delves into the intricate relationship between vitamin D, the immune system, gut flora, and the prevention of CRC. It presents a synthesis of epidemiological data, experimental studies, and clinical trials, highlighting the mechanisms by which vitamin D influences immune cell function, cytokine production, and inflammation. By enhancing the immune system's surveillance and anti-tumor activity, vitamin D may offer a promising avenue for CRC prevention. Furthermore, this comprehensive review delves into the prospective clinical applications of vitamin D supplementation and delineates the forthcoming avenues of research in this dynamic domain. Additionally, the paper tentatively outlines a spectrum of prophylactic impacts of vitamin D on CRC, emphasizing its significant potential in reducing CRC risk through shedding light on its mechanisms, encompassing antineoplastic mechanisms, influences on the immune system, and modulation of the gut microbiome.

The effect of previous SARS-CoV-2 infection on systemic immune responses in individuals with tuberculosis.

Background: The impact of previous SARS-CoV-2 infection on the systemic immune response during tuberculosis (TB) disease has not been explored. Methods: An observational, cross-sectional cohort was established to evaluate the systemic immune response in persons with pulmonary tuberculosis with or without previous SARS-CoV-2 infection. Those participants were recruited in an outpatient referral clinic in Rio de Janeiro, Brazil. TB was defined as a positive Xpert-MTB/RIF Ultra and/or a positive culture of Mycobacterium tuberculosis from sputum. Stored plasma was used to perform specific serology to identify previous SARS-CoV-2 infection (TB/Prex-SCoV-2 group) and confirm the non- infection of the tuberculosis group (TB group). Plasmatic cytokine/chemokine/growth factor profiling was performed using Luminex technology. Tuberculosis severity was assessed by clinical and laboratory parameters. Participants from TB group (4.55%) and TB/Prex-SCoV-2 (0.00%) received the complete COVID-19 vaccination. Results: Among 35 participants with pulmonary TB, 22 were classified as TB/Prex-SCoV-2. The parameters associated with TB severity, together with hematologic and biochemical data were similar between the TB and TB/Prex-SCoV-2 groups. Among the signs and symptoms, fever and dyspnea were significantly more frequent in the TB group than the TB/Prex-SCoV-2 group (p < 0,05). A signature based on lower amount of plasma EGF, G-CSF, GM-CSF, IFN-α2, IL-12(p70), IL-13, IL-15, IL-17, IL-1ß, IL-5, IL-7, and TNF-ß was observed in the TB/Prex-SCoV-2 group. In contrast, MIP-1ß was significantly higher in the TB/Prex-SCoV-2 group than the TB group. Conclusion: TB patients previously infected with SARS-CoV-2 had an immunomodulation that was associated with lower plasma concentrations of soluble factors associated with systemic inflammation. This signature was associated with a lower frequency of symptoms such as fever and dyspnea but did not reflect significant differences in TB severity parameters observed at baseline.

MEK-inhibitor treatment reduces the induction of regulatory T cells in mice after influenza A virus infection.

Regulatory T cells (Tregs) play a crucial and complex role in balancing the immune response to viral infection. Primarily, they serve to regulate the immune response by limiting the expression of proinflammatory cytokines, reducing inflammation in infected tissue, and limiting virus-specific T cell responses. But excessive activity of Tregs can also be detrimental and hinder the ability to effectively clear viral infection, leading to prolonged disease and potential worsening of disease severity. Not much is known about the impact of Tregs during severe influenza. In the present study, we show that CD4+/CD25+FoxP3+ Tregs are strongly involved in disease progression during influenza A virus (IAV) infection in mice. By comparing sublethal with lethal dose infection in vivo, we found that not the viral load but an increased number of CD4+/CD25+FoxP3+ Tregs may impair the immune response by suppressing virus specific CD8+ T cells and favors disease progression. Moreover, the transfer of induced Tregs into mice with mild disease symptoms had a negative and prolonged effect on disease outcome, emphasizing their importance for pathogenesis. Furthermore, treatment with MEK-inhibitors resulted in a significant reduction of induced Tregs in vitro and in vivo and positively influenced the progression of the disease. Our results demonstrate that CD4+/CD25+FoxP3+ Tregs are involved in the pathogenesis of severe influenza and indicate the potential of the MEK-inhibitor zapnometinib to modulate CD4+/CD25+FoxP3+ Tregs. Thus, making MEK-inhibitors even more promising for the treatment of severe influenza virus infections.

Development of α-Tocopherol Loaded PLGA Nanoparticles and Its Evaluation as a Novel Immune Adjuvant.

With the continuous development of preventive and therapeutic vaccines, traditional adjuvants cannot provide sufficient immune efficacy and it is of high necessity to develop safe and effective novel nanoparticle-based vaccine adjuvants. α-Tocopherol (TOC) is commonly used in oil-emulsion adjuvant systems as an immune enhancer, yet its bioavailability is limited by poor water solubility. This study aims to develop TOC-loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles (TOC-PLGA NPs) to explore the potential of TOC-PLGA NPs as a novel nanoparticle-immune adjuvant. TOC-PLGA NPs are prepared by a nanoprecipitation method and their physicochemical properties are characterized. It is shown that TOC-PLGA NPs are 110.8 nm, polydispersity index value of 0.042, and Zeta potential of -13.26 mV. The encapsulation efficiency and drug loading of NPs are 82.57% and 11.80%, respectively, and the cumulative release after 35 days of in vitro testing reaches 47%. Furthermore, TOC-PLGA NPs demonstrate a superior promotion effect on RAW 264.7 cell proliferation compared to PLGA NPs, being well phagocytosed and also promoting antigen uptake by macrophages. TOC-PLGA NPs can strongly upregulate the expression of co-stimulatory surface molecules and the secretion of cytokines. In conclusion, TOC-PLGA NPs can be a novel vaccine adjuvant with excellent biocompatibility and significant immune-enhancing activity.

A Janus Microsphere Delivery System Orchestrates Immunomodulation and Osteoinduction by Fine-tuning Release Profiles.

Bone regeneration is a well-orchestrated process synergistically involving inflammation, angiogenesis, and osteogenesis. Therefore, an effective bone graft should be designed to target multiple molecular events and biological demands during the bone healing process. In this study, a biodegradable gelatin methacryloyl (GelMA)-based Janus microsphere delivery system containing calcium phosphate oligomer (CPO) and bone morphogenetic protein-2 (BMP-2) is developed based on natural biological events. The exceptional adjustability of GelMA facilitates the controlled release and on-demand application of biomolecules, and optimized delivery profiles of CPO and BMP-2 are explored. The sustained release of CPO during the initial healing stages contributes to early immunomodulation and promotes mineralization in the late stage. Meanwhile, the administration of BMP-2 at a relatively high concentration within the therapeutic range enhances the osteoinductive property. This delivery system, with fine-tuned release patterns, induces M2 macrophage polarization and creates a conducive immuno-microenvironment, which in turn facilitates effective bone regeneration in vivo. Collectively, this study proposes a bottom-up concept, aiming to develop a user-friendly and easily controlled delivery system targeting individual biological events, which may offer a new perspective on developing function-optimized biomaterials for clinical use.

Microglial Piezo1 mechanosensitive channel as a therapeutic target in Alzheimer's disease.

Microglia are the resident macrophages of the central nervous system (CNS) that control brain development, maintain neural environments, respond to injuries, and regulate neuroinflammation. Despite their significant impact on various physiological and pathological processes across mammalian biology, there remains a notable gap in our understanding of how microglia perceive and transmit mechanical signals in both normal and diseased states. Recent studies have revealed that microglia possess the ability to detect changes in the mechanical properties of their environment, such as alterations in stiffness or pressure. These changes may occur during development, aging, or in pathological conditions such as trauma or neurodegenerative diseases. This review will discuss microglial Piezo1 mechanosensitive channels as potential therapeutic targets for Alzheimer's disease (AD). The structure, function, and modulation of Piezo1 will be discussed, as well as its role in facilitating microglial clearance of misfolded amyloid-ß (Aß) proteins implicated in the pathology of AD.

Bioactive Glass in Tissue Regeneration: Unveiling Recent Advances in Regenerative Strategies and Applications.

Bioactive glass (BG) is a class of biocompatible, biodegradable, multifunctional inorganic glass materials, which is successfully used for orthopedic and dental applications, with several products already approved for clinical use. Apart from exhibiting osteogenic properties, BG is also known to be angiogenic and antibacterial. Recently, BG's role in immunomodulation has been gradually revealed. While the therapeutic effect of BG is mostly reported in the context of bone and skin-related regeneration, its application in regenerating other tissues/organs, such as muscle, cartilage, and gastrointestinal tissue, has also been explored recently. The strategies of applying BG have also expanded from powder or cement form to more advanced strategies such as fabrication of composite polymer-BG scaffold, 3D printing of BG-loaded scaffold, and BG-induced extracellular vesicle production. This review presents a concise overview of the recent applications of BG in regenerative medicine. Various regenerative strategies of BG will be first introduced. Next, the applications of BG in regenerating various tissues/organs, such as bone, cartilage, muscle, tendon, skin, and gastrointestinal tissue, will be discussed. Finally, summarizing clinical applications of BG for tissue regeneration will conclude, and outline future challenges and directions for the clinical translation of BG.