I-Shou University

Glioblastoma multiforme (GBM) is the most common, aggressive, and dangerous lethal tumor in the brain, which develops in adults. Currently, the efficiency of chemotherapy treatment for GBM patients is still unsatisfactory. PW06 was synthesized by Dr. Lien's laboratory (China Medical University, Taichung, Taiwan), and it was demonstrated to induce cancer cell apoptosis in human pancreatic carcinoma MIA PaCa‐2 cells. However, the anti‐cancer activities of PW06 on human GBM cancer cells are not reported. Thus, herein, PW06 was investigated on the anticancer activity on human glioblastoma multiforme GBM 8401 cells. Both PI exclusion and Annexin V/PI double staining methods were conducted for investing cell viability and apoptosis in GBM 8401 cells, respectively; they were analyzed with flow cytometer assay. Results showed that PW06 decreased total viable cell number with the process of cell apoptosis in GBM 8401 cells. Both productions of reactive oxygen species (ROS) and Ca ²⁺ , affect mitochondria membrane potential (ΔΨm) levels, and activities of caspase‐3, ‐8, and ‐9 in GBM 8401 cells after exposure with PW06 were assayed by flow cytometer. Results showed that PW06 promoted ROS production and Ca ²⁺ release from ER but lowered the levels of ΔΨm, and it also induced higher activities in caspase‐3, ‐8, and ‐9 in GBM 8401 cells. Evaluation of protein expressions associated with apoptosis in GBM 8401 cells after being incubated with PW06 were conducted by Western blot analysis. Results show that PW06 increased GADD153, BiP, ATF‐6α, ATF‐6β, eIF2α, eIF2α pSer51 , CHOP, and caspase‐4, and they are associated with ER stress‐associated protein expression. However, it induced higher pro‐apoptotic proteins (Bax and Bad) expression and inhibited anti‐apoptotic proteins (Bcl‐2, Bcl‐xl, and Mcl‐1) expression, even promoting higher cleaved caspase‐8, ‐9, and ‐3 protein expression and increased EndoG and AIF in GBM 8401 cells. Collectively, it may suggest PW06 exits anti‐GBM activity to process cell apoptosis in the human GBM 8401 cells in vitro.

Background Diabetes mellitus is a highly burdensome metabolic disorder, affecting over 100 million people worldwide and leading to numerous complications. Among these, diabetic neuropathy is one of the most common, with approximately 60% of individuals with diabetes developing this condition. Current pharmacological treatments for diabetic neuropathy are often inadequate, providing limited efficacy and accompanied by a range of adverse effects. Non-invasive brain and nerve stimulation techniques have been proposed as potentially beneficial for diabetic neuropathy, though existing evidence remains inconclusive. This systematic review and network meta-analysis (NMA) aimed to evaluate the comparative efficacy of various non-invasive brain and nerve stimulation interventions in patients with diabetic neuropathy. Methods A systematic search of electronic databases was conducted to identify randomized controlled trials (RCTs) of non-invasive brain or nerve stimulation in patients with diabetic neuropathy, from inception to September 6, 2024. The primary outcome was the change in pain severity, while secondary outcomes included changes in quality of life and sleep disturbance. Acceptability was assessed through dropout rates (i.e., withdrawal from the study before completion for any reason). A frequentist-based NMA was performed, utilizing odds ratios (OR) and standardized mean differences (SMD) with 95% confidence intervals (95%CIs) as effect size measures. Results The NMA, which included 15 RCTs (totaling 1,139 participants, with a mean age of 61.2 years and a mean female proportion of 53.8%), evaluated 10 experimental interventions (1 control group, 4 non-invasive brain stimulation methods, and 5 non-invasive nerve stimulation methods). The analysis revealed that only transcutaneous electrical nerve stimulation (TENS) was associated with significantly greater improvements in pain severity (SMD = − 1.67, 95%CIs = − 2.64 to − 0.71) and sleep disruption (SMD = − 1.63, 95%CIs = − 2.27 to − 0.99) compared to the control group. None of the studied interventions showed significant differences in dropout rates or all-cause mortality compared to the control group. Conclusion This study provides comparative evidence supporting the use of specific brain and nerve stimulation interventions in managing diabetic neuropathy. Future well-designed RCTs with longer treatment durations are recommended to further validate the long-term efficacy of these interventions. Trial registration PROSPERO CRD42024587660.

Overexpression of histone deacetylase 6 (HDAC6) is implicated in tumorigenesis, invasion, migration, survival, apoptosis, and growth of various malignancies, making it a promising target for cancer treatment. Building on our previous work, we report a novel series of tetrahydro-β-carboline-piperazinedione derivatives as HDAC6 inhibitors. Structural modifications were introduced at the 6-aryl group, with the m-bromophenyl derivative (9c) emerging as the most potent HDAC6 inhibitor, exhibiting an IC 50 of 7 nM. Compound 9c demonstrated robust growth inhibitory activity across 60 cancer cell lines from the NCI panel, with a mean GI 50 of 2.64 μM and a GI 50 below 5 μM for nearly all tested lines, while exhibiting significantly lower cytotoxicity towards non-tumor cell lines. The triple-negative breast cancer cell line MDA-MB-231 was selected for further investigation of 9c's cellular effects. 9c selectively increased the acetylation of non-histone α-tubulin in MDA-MB-231 cells, confirming its HDAC6 selectivity. Furthermore, 9c effectively induced apoptosis, caused apoptotic sub-G1 phase accumulation, upregulated pro-apoptotic caspase-3, and downregulated anti-apoptotic Bcl-2. Notably, 9c reduced the expression of programmed death-ligand 1 (PD-L1), a key immune checkpoint protein that enables tumor cells to evade immune surveillance, highlighting its potential role in enhancing anti-tumor immunity. In addition, 9c inhibited phosphorylated extracellular signal-regulated kinase (ERK)1/2, a central signaling pathway that drives cell proliferation, survival, and migration, further highlighting its significance in suppressing tumor progression and growth. In migration assays, 9c impaired cell motility, achieving 80% gap closure inhibition in a wound-healing assay. Collectively, these findings underline compound 9c as a highly promising candidate for the treatment of triple-negative breast cancer, with the added benefits of PD-L1 and ERK inhibition for potential synergy in enhancing anti-tumor immunity and reducing tumor cell proliferation.

Background This study aimed to investigate the frequently overlooked symptoms of cold hypersensitivity and heavy legs related to varicose veins in a large sample of patients. Methods Data on 8782 adults aged 30–70 years without a history of cancer were sourced from the Taiwan Biobank between 2008 and 2020. Varicose veins, cold hypersensitivity and heavy leg sensations were assessed using questionnaires and analysed using logistic regression models with various covariates. Statistical analyses were performed, with analysis of variance for continuous variables and χ ² tests for categorical variables at a significance level of 0.05. Results Our analysis showed significant associations between varicose veins, cold hypersensitivity, and heavy legs (p<0.0001). Logistic regression models showed that moderate and severe cold hypersensitivity increased the risk of varicose veins with ORs of 1.490 (95% CI 1.205 to 1.842) and 1.894 (95% CI 1.546 to 2.320), respectively. Similarly, heavy legs were strongly associated with varicose veins (OR 4.239, 95% CI 3.381 to 5.315), and the interaction between cold hypersensitivity and heavy legs was significant (p=0.0009). Notably, the greatest risk for varicose veins was observed in individuals with heavy legs and severe cold hypersensitivity (OR 7.135, 95% CI 4.980 to 10.221). Conclusions The results of this study highlight the clinical significance of considering cold hypersensitivity and heavy legs as vital symptoms for diagnosing varicose veins, particularly in the absence of arterial disorders, which can improve diagnostic accuracy and patient outcomes.

This chapter is an editorial overview and interpretation of the most critical topics concerning future development of intellectual capital (IC) theory, research and practice. Based on the 16 ground-breaking and future-oriented core chapters in this book, we identify eight emerging themes for futurizing the field of IC: 1) the need for multilevel approach towards IC; 2) an examination of IC dynamics; 3) redefining of value and economic models at the basis of IC; 4) a better recognition of sustainability and ethics in IC research; 5) a focus on the role of AI in IC; 6) a renewed emphasis on humans and culture; 7) a focus on non-rational and non-technological aspects of IC; and 8) an interdisciplinary approach towards research. We also compile a list of theoretical and practical highlights to futurizing IC, provided by the authors of the individual chapters in this book. The ideas presented in this chapter contribute to opening up new perspectives for the development of IC theory and practice, and inviting scholars and practitioners to a global and future-oriented discussion on IC.

This editorial introductory chapter sets the stage for a forward-looking exploration of intellectual capital (IC) in both theoretical and practical contexts. It addresses the evolving landscape of IC in an era marked by rapid technological, institutional and socio-political disruptions and demonstrates the need for futurizing the field of IC. By providing a cohesive framework for the book’s thematic sections, this chapter highlights the novel viewpoints and visions from leading experts concerning future directions for IC research and practice. It also summarizes the book’s 16 main chapters and discusses how each of them pushes the boundaries of conceptual and empirical insights in the field of IC. This comprehensive introduction contributes to deeper understanding of the proposed new paradigms to align IC theory and practice with future economic, social, and technological changes.

The gait analysis has been applied in many fields, such as the assessment of falling, force evaluation in sports, and gait disorder detection for neuromuscular diseases. Its main recording techniques include video cameras and wearable sensors. However, the present methods involve measuring surface electromyograms (sEMGs) to analyze muscle activities. The primary goal of this study is to estimate gait parameters under different power capacity of muscle by sEMGs measured from lower limbs. A self-made wireless device recorded sEMGs from two muscles of each foot, and GaitUp Physilog®5 sensors captured gait parameters from 18 participants under running as references. Four features including median frequency (MDF), waveform length (WL), standard deviation (SD), and sample entropy (SampEn), were extracted from the sEMG data. The analysis utilized three machine learning models (Random Forest, CatBoost, XGBoost), evaluated through various evaluation metrics. Additionally, 5-fold cross-validation was conducted to assess the influence of muscle fatigue on the estimation of gait parameters. The results show that all models successfully estimated 20 gait parameters, all showing a Pearson correlation coefficient (PCC) above 0.800. However, the performance of models significantly depends on the condition of muscle fatigue. This study represents a significant advancement in gait analysis, providing a comprehensive method for estimating gait parameters from sEMG signals, with important implications for mobile health applications.

Purpose In epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC) patients treated with EGFR-tyrosine kinase inhibitors (TKIs), transformation to small-cell lung cancer (SCLC) is associated with poor outcomes, and the optimal treatment strategy is unclear. This study aimed to investigate the clinical factors and treatments associated with outcomes in this group. Patients and Methods This retrospective multicenter study enrolled patients with SCLC transformed from advanced NSCLC after progression on EGFR-TKI treatment. We analyzed clinical and demographic characteristics, first-line EGFR-TKI treatments, and subsequent regimens to identify factors associated with clinical outcomes. Results Twenty-seven patients diagnosed with SCLC transformation after EGFR-TKI therapy between 2018 and 2023 were enrolled, most of whom had an EGFR exon 19 deletion (67%). The subsequent treatment regimens included traditional chemotherapy (CT) in 12 patients (44%), combined CT/EGFR-TKI in 10 patients (37%), and combined CT/immunotherapy in 5 patients (19%). The median progression-free survival (PFS) with first-line EGFR-TKI treatment, subsequent SCLC treatment, and overall survival (OS) were 16.1 months, 6.4 months, and 39.5 months, respectively. The overall response rate (ORR), disease control rate (DCR), and median PFS for subsequent treatments were 38.5%, 69.2%, and 6.4 months, respectively. The DCRs for subsequent CT, CT/TKI, and CT/immunotherapy were 41.7%, 88.9%, and 100%, respectively. ORR and PFS were higher in the CT/TKI (44.4% and 7.2 months) and CT/immunotherapy (80.0% and 11.3 months) groups compared to CT (16.7% and 3.7 months), but these differences were not statistically significant. Univariate and multivariate analyses showed no significant differences in PFS and OS among treatments. Conclusion In patients with SCLC transformed from advanced NSCLC after EGFR-TKI treatment, adding immunotherapy and EGFR-TKI to CT improved DCR and showed trends in ORR and PFS, but did not provide an OS benefit. More prospective studies with varied therapeutic approaches are needed to confirm these findings.

Melioidosis outbreaks in Taiwan frequently coincided with severe typhoons. Over a 20-year period, 782 cases of melioidosis were reported, with outbreaks often clustering in a specific hotspot area. We hypothesized that the unique hilly terrain in this hotspot trapped contaminated aerosols generated from northern to northwestern farming land within the area and restricted their spread beyond it. Across Taiwan, and particularly within the hotspot, weekly melioidosis incidence was significantly correlated with heavy rainfall and strong wind speed with time lags of 0, 1 and 2 weeks. When rainfall exceeded 200 mm and wind gust speeds reached over 20 m/sec, melioidosis outbreaks were frequently observed. Additionally, melioidosis incidence was associated with riverbank repair activities, indicating severe flooding caused by typhoons. Environmental confounding factors, such as CH₄, CO, NO, NO₂, NO x , O₃, particulate matter (PM) 10 , PM 2.5 , SO₂, and total hydrocarbon (THC), fluctuated seasonally but were not correlated with melioidosis cases. Aerosol sampling revealed that concentrations of contaminated aerosols were markedly higher north of the hill, where farming land was more prevalent, compared to the south, which had no farming land and was primarily residential. In addition to heavy rainfall and strong wind speed, shifts in wind direction from southwesterly to northwesterly during typhoons appeared to concentrate aerosols in the northern area but not in the south. Higher seropositive rates for Burkholderia pseudomallei antibodies in northern residents, compared to those in the south, further suggested increased exposure to pathogen-laden aerosols in the northern hotspot. This study demonstrated that heavy rainfall, combined with strong directional winds, generated high concentrations of contaminated aerosols from farming land in specific hilly terrains, leading to localized melioidosis outbreaks. It provided a valuable example of geographical, and climatic factors driving the formation of melioidosis hotspots in subtropical regions such as southern Taiwan.

Background This multi-institute retrospective cohort study investigated the association between preoperative anemia and postoperative acute kidney injury (AKI) in patients undergoing metabolic and bariatric surgery (MBS). Methods Using the TriNetX research network, we identified adult patients who underwent MBS between January 2010 and December 2024. Patients were categorized as anemic or non-anemic based on preoperative hemoglobin levels (hemoglobin < 12 g/dL for females and < 13 g/dL for males). Propensity score matching was performed to balance the baseline characteristics. The primary outcome was AKI within 30 days of MBS. The secondary outcomes included infections, intensive care unit admission, surgical complications, and deep vein thrombosis. Analyses were conducted separately for female and male patients, with additional sensitivity analyses for the female subgroups. Results After propensity score matching, preoperative anemia was significantly associated with an increased risk of postoperative AKI in females (1.51% vs. 0.71%, odds ratio (OR) 2.14, 95% confidence interval (CI) 1.53–2.98, p < 0.0001) (n = 7144 pairs). This association persisted in all sensitivity analyses. Even mild anemia (hemoglobin 10–12 g/dL) was associated with a higher AKI risk (OR 1.62, p = 0.004) in female patients. In males (n = 971 pairs), anemia similarly increased the AKI risk (4.94% vs. 2.68%, OR 1.89, 95% CI 1.16–3.07, p = 0.009). No significant differences were observed in secondary outcomes for either sex. Conclusion Preoperative anemia is independently associated with an increased risk of postoperative AKI in both female and male patients undergoing MBS, suggesting that preoperative anemia screening and management could be important for reducing postoperative kidney complications in this population. Graphical Abstract

Altered histone deacetylase 6 (HDAC6) expression and function have been linked to cancer progression, positioning it as a promising therapeutic target for cancer treatment. Herein, we introduce HDAC6 inhibitors based on the tetrahydro-β-carboline scaffold, with compound 18d exhibiting the strongest HDAC6 inhibitory potency, achieving an IC50 of 1.3 nM. Compound 18d exhibited significant growth inhibitory activity against an NCI panel of 60 human cancer cell lines with a minimal cytotoxic effect on non-tumor cells. In vitro mechanistic investigations were conducted in HCT-116 colorectal cancer cells where the capability of 18d to enhance the acetylation of α-tubulin (HDAC6 substrate) rather than nuclear H3 histone (HDAC1 substrate) confirmed selective inhibition of HDAC6 subtype. Additionally, compound 18d was observed to suppress the S phase and promote accumulation in the apoptotic sub-G1 phase, potentially through increasing cleaved caspase 3 and reducing Bcl-2 levels in HCT-116 cells. A wound healing assay also elicited the ability of 18d to hinder cell migration. Notably, 18d could suppress the phosphorylation of extracellular signal-regulated kinase (ERK)1/2, a crucial signaling pathway implicated in cancer cell proliferation, migration and apoptosis. Moreover, downregulation of the critical immune checkpoint protein programmed death-ligand 1 (PD-L1) revealed a potential role of 18d in augmenting immune response towards tumor cells. In summary, these findings highlight 18d's dual role in direct tumor growth suppression and immune system sensitization, highlighting a broader cancer therapeutic potential beyond conventional HDAC inhibition.

This study investigated the correlation between metformin use and diabetic peripheral neuropathy (DPN) risk in patients with type 2 diabetes mellitus (T2DM) and its dose-dependent relationship. The study included new-onset T2DM patients from 2002 to 2013. Patients were divided into two groups based on metformin treatment, and DPN risk was assessed at 2- and 5-year follow-ups. After adjusting for various factors, two logistic models, metformin cumulative defined daily dose (cDDD) and metformin treatment intensity (defined daily dose [DDD]/month), evaluated the metformin-DPN risk association. Results showed that patients with metformin cDDD < 300, 300–500, and > 500 had higher DPN risk at both follow-ups. Odds ratios (ORs) and confidence intervals (CIs) for DPN were 1.74 (1.69–1.79), 2.05 (1.81–2.32), and 2.36 (1.34–4.16) at 2 years and 1.63 (1.60–1.65), 1.82 (1.69–1.96), and 2.17 (1.56–3.03) at 5 years. Similarly, patients with < 10, 10–25, and > 25 DDD/month had higher DPN risk at both follow-ups. Metformin use correlated with DPN risk in T2DM patients, with a dose-dependent relationship. Higher metformin cDDD or treatment intensity increased DPN risk. However, the absence of vitamin B12 data limits the understanding of the underlying mechanisms. Well-designed, large-scale studies are required to evaluate the potential risks of metformin therapy for DPN in patients with T2DM.

Background Glucagon-like peptide-1 (GLP-1) receptor agonists and sodium–glucose cotransporter 2 (SGLT2) inhibitors represent a new generation of antihyperglycemic agents that operate through mechanisms distinct from conventional diabetes treatments. Beyond their metabolic effects, these medications have demonstrated neuroprotective properties in preclinical studies. While clinical trials have explored their therapeutic potential in established neurodegenerative conditions, their role in disease prevention remains unclear. We conducted a network meta-analysis (NMA) to comprehensively evaluate the prophylactic benefits of these agents across multiple neurodegenerative diseases and identify the most promising preventive strategies. Methods We systematically searched PubMed, Embase, ClinicalKey, Cochrane CENTRAL, ProQuest, ScienceDirect, Web of Science, and ClinicalTrials.gov through October 24th, 2024, for randomized controlled trials (RCTs) of GLP-1 receptor agonists or SGLT2 inhibitors. Our primary outcome was the incidence of seven major neurodegenerative diseases: Parkinson’s disease, Alzheimer’s disease, Lewy body dementia, multiple sclerosis, amyotrophic lateral sclerosis, frontotemporal dementia, and Huntington’s disease. Secondary outcomes included safety profiles assessed through dropout rates. We performed a frequentist-based NMA and evaluated risk of bias with Risk of Bias tool. The main result of the primary outcome in the current study would be re-affirmed via sensitivity test with Bayesian-based NMA. Results Our analysis encompassed 22 RCTs involving 138,282 participants (mean age 64.8 years, 36.4% female). Among all investigated medications, only dapagliflozin demonstrated significant prophylactic benefits, specifically in preventing Parkinson’s disease (odds ratio = 0.28, 95% confidence intervals = 0.09 to 0.93) compared to controls. Neither GLP-1 receptor agonists nor other SGLT2 inhibitors showed significant preventive effects for any of the investigated neurodegenerative conditions. Drop-out rates were comparable across all treatments. Conclusions This comprehensive NMA reveals a novel and specific prophylactic effect of dapagliflozin against Parkinson’s disease, representing a potential breakthrough in preventive neurology. The specificity of dapagliflozin’s protective effect to Parkinson’s disease might rely on its highly selective inhibition to SGLT2. These findings provide important direction for future research and could inform preventive strategies for populations at risk of Parkinson’s disease. Trial registration PROSPERO CRD42021252381.

The malignant progression of human cancer is dictated by specific regulatory hubs coordinating multiple signaling modules. Identifying key oncogenic hubs of human cancers may lay the groundwork for developing breakthrough therapeutic strategies. Actin-like 6A (ACTL6A; BAF53A) was originally identified as a chromatin remodeling factor involved in the transcriptional regulation of genes, especially in stem and progenitor cells. The preponderance of evidence revealed the overexpression of ACTL6A in most cancers and its crucial role in various malignant phenotypes, including cell cycle progression, cancer stemness, epithelial-to-mesenchymal transition, redox and glucose metabolism, and DNA replication and repair. Interestingly, emerging data suggest that the oncogenic function of ACTL6A is mediated through diverse mechanisms beyond its canonical function in transcriptional regulation, including notably the stabilization of oncoproteins and stemness factors, such as YAP, VPS72, and MYC. Here, we describe the isoforms and the putative functional domains of ACTL6A. We summarize the expression pattern and prognostic significance of ACTL6A in human cancers and the upstream regulatory mechanisms of its expression. We summarize recent progress in understanding the diverse pro-oncogenic functions of ACTL6A and emphasize its pleiotropic mechanisms of action as a regulatory hub of cancer stemness and progression. The review highlights the importance and the potential utilities of characterizing ACTL6A, which may imply molecularly informed diagnostics and therapeutics to improve the outcome of cancer patients.

Background The impact of preoperative coronavirus disease (COVID-19) on outcomes after metabolic and bariatric surgery (MBS) remains incompletely understood, as previous studies were conducted early in the pandemic, when viral strains and management differed. Methods Using the TriNetX database, we conducted a retrospective analysis of patients who underwent MBS between June 2022 and December 2024. Patients with COVID-19 within 4 weeks before surgery were propensity-score matched 1:1 with controls without prior COVID-19 based on demographics, obesity-associated medical condition, and laboratory values. The primary outcome was the incidence of postoperative pulmonary complications (i.e., pneumonia or acute respiratory failure), while the secondary outcomes included the incidence of acute kidney injury (AKI), intensive care unit (ICU) admission, other infections (i.e., surgical site infection or urinary tract infection), mortality, and emergency department (ED) visits. Results Among 34,652 matched patients, 30-day pulmonary complications showed no significant difference between the COVID-19 and control groups (odds ratio[OR]: 0.898, 95%CI:0.674–1.197, p = 0.4646). However, the COVID-19 group experienced higher rates of AKI (OR:1.407, 95%CI:1.087–1.823, p = 0.0093) and ED visits (OR:1.169, 95%CI:1.082–1.264, p < 0.0001). Other secondary outcomes were similar between the groups. COPD, anemia, and old age were significant risk factors for pulmonary complications. Risk factors for AKI include chronic kidney disease, male sex, anemia, diabetes mellitus, and cardiovascular diseases. Conclusion Recent preoperative COVID-19 was not associated with increased risk of pulmonary complications following MBS, suggesting surgery need not be delayed for this concern. However, enhanced monitoring of renal complications and post-discharge care may be warranted in patients with identified risk factors.

Traumatic or degenerative defects of articular cartilage impair joint function, and the treatment of articular cartilage damage remains a challenge. By mimicking the cartilage extracellular matrix (ECM), exosome-seeded cryogels may enhance cell proliferation and chondral repair. ECM-based cryogels were cryopolymerized with gelatin, chondroitin sulfate, and various concentrations (0%, 0.3%, 0.5%, and 1%) of hyaluronic acid (HA), and their water content, swelling ratio, porosity, mechanical properties, and effects on cell viability were evaluated. The regenerative effects of bone marrow-derived mesenchymal stem cell (BM-MSC)-derived exosome (at a concentration of 10⁶ particles/mL)-seeded 0.3% HA cryogels were assessed in vitro and in surgically induced male New Zealand rabbit cartilage defects in vivo. The water content, swelling ratio, and porosity of the cryogels significantly (p < 0.05) increased and the Young’s modulus values of the cryogels decreased with increasing HA concentrations. MTT assays revealed that the developed biomaterials had no cytotoxic effects. The optimal cryogel composition was 0.3% HA, and the resulting cryogel had favorable properties and suitable mechanical strength. Exosomes alone and exosome-seeded cryogels promoted chondrocyte proliferation (with cell optical densities that were 58% and 51% greater than that of the control). The cryogel alone and the exosome-seeded cryogel facilitated ECM deposition and sulfated glycosaminoglycan synthesis. Although we observed cartilage repair via Alcian blue staining with both the cryogel alone and the exosome-seeded cryogel, the layered arrangement of the chondrocytes was superior to that of the control chondrocytes when exosome-seeded cryogels were used. This study revealed the potential value of using BM-MSC-derived exosome-seeded ECM-based cryogels for cartilage tissue engineering to treat cartilage injury.