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Levodopa, co-administered with the dopa decarboxylase inhibitor carbidopa, remains the gold standard for treating Parkinson&#39;s Disease; however, due to rapid degradation, only about 1% of orally administered levodopa crosses the blood-brain barrier.
This study developed and validated a robust high-performance liquid chromatography method to quantify levodopa, achieving reliable linearity across multiple replicates. Various buffer systems and pH conditions were tested, with phosphate buffered saline (PBS) at pH 6 and supplemented with glutamic acid hydrochloride offering the most stable environment. With stability confirmed, levodopa was successfully incorporated into a hydrogel matrix using poly(vinyl alcohol) (PVA), and hydrogel-forming microneedles using poly(methyl vinyl
ether/maleic acid), polyethylene glycol, and sodium bicarbonate. These microneedles
demonstrated sufficient mechanical strength to penetrate Parafilm “M” skin simulants, suggesting potential for effective skin permeation.
This work represents a significant step toward creating an alternative levodopa delivery system that could reduce gastrointestinal side effects, improve patient adherence, and offer more consistent plasma drug levels, thereby alleviating the motor fluctuations common with oral levodopa therapy. Although not curative, the finding supports further investigation into in vitro permeation studies and eventual clinical translation of microneedle-based patch system for Parkinson’s disease management.

AMA Research Challenge 2025 

Development and Characterization of Levodopa Microneedle Patches for Parkinson&#39;s Disease

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AMA Research Challenge 2022

Welcome to the largest national, multi-specialty research event featuring research from 750 medical students, residents and fellows, and international medical graduates.


Levodopa, co-administered with the dopa decarboxylase inhibitor carbidopa, remains the gold standard for treating Parkinson's Disease; however, due to rapid degradation, only about 1% of orally administered levodopa crosses the blood-brain barrier.
This study developed and validated a robust high-performance liquid chromatography method to quantify levodopa, achieving reliable linearity across multiple replicates. Various buffer systems and pH conditions were tested, with phosphate buffered saline (PBS) at pH 6 and supplemented with glutamic acid hydrochloride offering the most stable environment. With stability confirmed, levodopa was successfully incorporated into a hydrogel matrix using poly(vinyl alcohol) (PVA), and hydrogel-forming microneedles using poly(methyl vinyl
ether/maleic acid), polyethylene glycol, and sodium bicarbonate. These microneedles
demonstrated sufficient mechanical strength to penetrate Parafilm “M” skin simulants, suggesting potential for effective skin permeation.
This work represents a significant step toward creating an alternative levodopa delivery system that could reduce gastrointestinal side effects, improve patient adherence, and offer more consistent plasma drug levels, thereby alleviating the motor fluctuations common with oral levodopa therapy. Although not curative, the finding supports further investigation into in vitro permeation studies and eventual clinical translation of microneedle-based patch system for Parkinson’s disease management.

Development and Characterization of Levodopa Microneedle Patches for Parkinson's Disease

technical paper

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### Background
Despite current treatment strategies for atherosclerotic vascular disease focusing on lifestyle modification and lowering cholesterol, a significant residual risk of major atherosclerotic complication remains, prompting investigation into lipoprotein(a) [Lp(a)] as a potential predictive biomarker. The objective of this study was to determine the utility of Lp(a) in identifying patients at high risk of incident extracoronary atherosclerotic vascular disease and complications. 

### Methods
Data from 460,544 participants in the UK Biobank with prospectively measured Lp(a) concentrations were included in this analysis. Cox proportional hazards regressions modeled the associations of Lp(a) concentrations with incident peripheral arterial disease (PAD) and incident carotid artery stenosis, and progression to the first major adverse limb event (MALE) and the first stroke, respectively.

### Results
Of the study participants, the median [IQR] age at study enrollment was 58 [51 – 64] years, 54.2% were male, 94.4% European, 5.5% had diabetes, and 10.5% were smokers. Over a median follow-up time of 13.6 [12.9 – 14.4] years, 6,347 (1.4%) and 1,972 (0.43%) developed the first incidence of PAD and carotid stenosis, respectively. Among participants with prevalent PAD and carotid stenosis at enrollment, 196 (2.7%) and 67 (1.9%) progressed to the first incidence of MALE and stroke, respectively. Median Lp(a) concentrations were significantly different in those without atherosclerotic vascular disease at 19.5 nmol/L [7.6-73.5] compared to incident PAD at 25.3 nmol/L [8.3-107.3], progression to MALE at 33.3 nmol/L [8.7-158.2], incident carotid stenosis at 29.5 nmol/L [8.5-116.3], and carotid stenosis progression to stroke at 37.8 nmol/L [11.1-158.3]. The risk estimate per 75 nmol/L Lp(a) for incident PAD (HR 1.18, 95% CI 1.15-1.20, p-value<0.0001) was similar to incident carotid stenosis (HR 1.17, 95% CI 1.13-1.20, p-value<0.0001). Among participants with PAD, those with high Lp(a) concentrations were at 1.57 times the risk of developing MALE than participants with normal Lp(a) concentrations (95% CI 1.14-2.16, p-value=0.006). Among participants with carotid stenosis, participants had 1.40 times the risk of developing an ischemic stroke with high Lp(a) concentrations, although this was not significant (95% CI 0.81-2.40, p-value=0.228).

### Conclusion
High concentrations of Lp(a) are associated with both incident extracoronary atherosclerotic vascular disease and progression to major complications.


Lipoprotein(a) is a Prognostic Marker of Extracoronary Atherosclerotic Vascular Disease Progression

Alzheimer’s disease (AD) is a debilitating dementia that affects about seven million Americans. Oligodendrocytes and myelin degeneration have been noted as features of AD, with demyelination beginning in preclinical disease. However, the mechanisms underlying oligodendrocyte and myelin decay remain poorly understood. Here, we show how transcriptional stress coupled-DNA damage accumulates in preclinical disease, and outline a novel pathway downstream of this DNA damage resulting in activation of the Type I interferon response. In vitro, we find that upon DNA damage, oligodendrocytes activate Stimulator of Interferon Genes (STING), a mediator of the DNA damage-Type I interferon signaling axis, and this drives myelin deficits in vitro. Oligodendrocyte lineage-specific deletion of STING in the 5XFAD murine AD model reduces demyelination, microgliosis, neurodegeneration, and plaque formation. Finally, loss of STING in oligodendroglial cells rescues deficits in spatial memory and learning in the 5XFAD model, as shown by Barnes Maze latencies. Our findings uncover a previously overlooked and key role for oligodendrocytes as active drivers of neurodegeneration in Alzheimer’s Disease.

Oligodendrocyte genomic stress-induced interferon responses drive progression of Alzheimer’s Disease

### Background 
White matter hyperintensities (WMH) are MRI-detected markers of small vessel disease associated with cognitive decline and Alzheimer’s disease (AD). African Americans (AAs) are disproportionately burdened by cerebrovascular risk factors, yet remain significantly underrepresented in WMH research. This disparity limits the generalizability of findings and may obscure key determinants of disease progression in diverse populations. Identifying how race and related factors influence WMH burden is critical to improving equity in Alzheimer’s care and prevention. This study aimed to examine whether racial differences exist in WMH burden across the AD spectrum, while accounting for other demographic and clinical variables. 

### Methods 
We analyzed cross-sectional MRI and clinical data from 1,649 participants in the Alzheimer’s Disease Neuroimaging Initiative (ADNI): 682 cognitively normal (CN), 584 with mild cognitive impairment (MCI), and 383 with AD. Of these, 124 participants (7.5%) identified as African American: CN (n=70), MCI (n=39), and AD (n=15). Linear mixed effects models were used to evaluate the effect of race, cognitive status, time since first MRI, age, sex, education, intracranial volume (ICV), MRI acquisition type, and APOE ε4 status on total WMH volume. 

### Results 
Older age, greater time since MRI, and larger ICV were significantly associated with increased WMH burden across cognitive groups. Use of FLAIR imaging was negatively associated with WMH volume, reflecting differences in image acquisition sensitivity. Higher educational attainment was linked to lower WMH burden, suggesting a possible neuroprotective effect. The most pronounced associations were observed within the AD subgroup. After adjusting for all covariates, race was not a statistically significant independent predictor of WMH burden. 

### Conclusion 
Although race did not independently predict WMH burden, other structural and demographic factors, including age, education level, and MRI technique, significantly influenced WMH volume. These findings highlight the complex interplay between biological, social, and technical variables in shaping cerebrovascular brain aging. Greater inclusion of African American participants in future studies is essential to better understand race-related mechanisms and to design interventions that equitably address WMH accumulation and its cognitive consequences.

Understanding the Impact of Race on White Matter Hyperintensities in Alzheimer’s Disease: Findings from the ADNI Study

### Background
Pheochromocytomas and paragangliomas (PPGLs) are rare neural-crest derived tumors with one of the highest germline heritability rates of all neoplasias (40%) and lead to lifelong surveillance. Succinate dehydrogenase (SDHx)-deficient PPGLs are associated with an aggressive disease course, with an overall survival of 50% at 5 years for individuals with metastatic disease. Predicting primary tumor development or metastatic disease progression throughout the life course with imaging/plasma metanephrines and histopathological scoring systems have limitations. The discovery of metabolic rewiring of SDHx deficiency at the tumor level holds promise as a non-invasive disease biomarker.

### Methods
Harnessing the connection of SDHx to metabolic dysfunction, we performed prospective plasma metabolomics (liquid chromatography/mass spectrometry) on 122 well-phenotyped patients, 49.1% of whom were SDHx carriers, at one or multiple time points during a patient’s clinical journey. Concurrently, tissue (adrenal, muscle, heart, brain) and plasma metabolomics of a novel SDHx deficient murine model were utilized for validation of patient-derived biomarkers.

### Results
Metabolomics of patient plasma samples revealed that succinate is a sensitive and specific biomarker of SDHx deficiency (ROC 0.825 – 75% sensitivity and 79.5% specificity), and succinate:glycine ratios improved the ROC to 0.856. With deep phenotyping, we found that age, BMI, and sex trended with succinate. Specifically, succinate levels were significantly correlated with female sex and increasing age. Of those with tumors, succinate had a ROC of 0.933, distinguishing SDHx deficient (including WT gastrointestinal stromal tumors (GISTs), which lack clinical biomarkers of disease) and proficient tumors. Five individuals with SDHx deficient tumors with multiple blood samples developed progressive disease, all of which were correspondingly reflected in succinate elevations. Succinate was not sensitive to treatment response (of both radiotherapy and surgery). Murine SDHx deficient adrenal glands had significantly elevated succinate concentrations however there were no significant changes in succinate plasma concentrations compared to WT mice.

### Conclusion
These findings suggest that plasma metabolomics holds promise as a screening test, especially in resource-poor settings or when rapid clinical decision making is necessary, as genetic testing can often take weeks, if not months, in some clinical settings. Prior to clinical application, further definition of the normal distribution of succinate levels in the general population is required. The mechanism underlying the unexpected finding of elevated succinate in SDHx carriers is a focus of future research. Overall, plasma metabolomics is a novel companion diagnostic for asymptomatic SDHx carriers and individuals with SDHx deficient tumors, of not only PPGLs but also GISTs.

Plasma Biomarkers for SDHx Deficient Pheochromocytomas and Paragangliomas

### Introduction
Estrogen-related receptors (ERRs) are nuclear receptors essential for postnatal cardiac maturation. Our recent studies have shown that ERRs are necessary for coordinated activation of cardiomyocyte metabolic and structural gene programs through interactions with PGC-1 coactivators and cardiogenic factors such as GATA4. In heart failure (HF), ERR transcriptional programs may revert to a fetal-like state, leading to metabolic inefficiency and energy starvation.

### Methods
To better understand ERRs’ role in HF, 176 SNPs from a recent HF GWAS were mapped onto the human cardiomyocyte cistrome to identify potential HF-associated variants proximal to ERRγ and/or ERRα binding regions. Overlaps were analyzed for ERR binding motifs with an 80% position-weight matrix threshold. Permutation testing was performed to determine if HF-associated variants were found more frequently than expected near ERR binding regions. Hypergeometric testing assessed whether HF-associated SNPs were enriched in ERR binding regions compared to genome-wide SNPs, with per-chromosome p-values combined using Fisher’s method. Stratified linkage disequilibrium score regression (S-LDSC) was performed to quantify whether SNPs within ERR binding regions disproportionately contributed to HF heritability compared to genome-wide averages.

### Results
Both permutation and hypergeometric testing showed significant enrichment of HF-associated variants proximal to ERR binding regions (p < 0.05). The number of overlaps increased with the size of the flanking region, ranging from 48 at 5 kb to 135 at 50 kb. Consensus ERR motifs were identified in 6.4% of ERRγ overlaps and 4.0% of ERRα overlaps. S-LDSC demonstrated notable HF heritability enrichment within ERRγ binding regions (enrichment score: 8.8 ± 3.0, p = 0.010), whereas ERRα showed non-significant enrichment (3.8 ± 3.3, p = 0.426), and GATA4 showed negligible enrichment (−0.4 ± 5.27, p = 0.786).

### Conclusion
This computational analysis reveals significant enrichment of HF-associated SNPs in or near genomic regions containing ERR transcription factors, highlighting ERR-driven transcriptional networks as potentially important mechanisms underlying heart failure development. These results establish a platform for future functional experimental studies to determine the impact of HF-associated variants on ERR-mediated transcriptional regulatory function and additional computational analyses to clarify the precise biological roles of ERRs in HF progression.

Heart Failure-Associated SNPs Are Enriched in Estrogen-Related Receptor Binding Regions

### Background 
Quality assessments relying solely on structured EHR data do not capture note-documented explanations for apparent non-adherence to lipid management guidelines. Large language models (LLMs) present a promising approach for extracting this information at scale.

### Purpose 
To evaluate the accuracy and impact of LLMs when applied to assess adherence to lipid management guidelines in CAD. 

### Methods 
We used structured EHR data to analyze LDL-C levels and statin use of patients with ASCVD seen in cardiology clinics at a large academic medical center from 2022-2024. We then applied GPT-4o with zero-shot, chain-of-thought prompting to free-text cardiology clinic notes to (1) identify external LDL-C values documented within the notes of patients without a recent in-system lipid panel and (2) infer reasons for statin non-use among those with LDL-C ≥70 mg/dL. We validated GPT-4o's accuracy through manual review of 500 randomly selected charts. 

### Results 
Among 8,595 patients (median age 71.0 years, 61.5% male, 70.8% White) initially identified, 53.6% were on high-intensity statins and 38.1% had LDL-C <70 mg/dL. GPT-4o confirmed a CAD diagnosis in 6,534 (76.0%) patients (Figure); within this group, GPT-4o identified external lipid panels in n=403 (6.2%), high-intensity statin use (n=59, 0.7%), and statin intolerance (n=804, 12.3%) documented in notes but not captured in structured fields (PPV 0.91-1.00). Among patients with GPT-4o-confirmed CAD and updated medication/laboratory data had higher measured rates of high-intensity statin use (61.4% vs. 53.6%) and LDL-C <70 mg/dL (44.1% vs. 38.1%). Excluding statin-intolerant patients further increased high-intensity statin use to 68.4%. Among patients with LDL-C ≥70 mg/dL not on high-intensity statins (N=1,164), GPT-4o-extracted reasons for nonuse were clinician decision (13.0%), intolerance (38.5%), patient preference (8.2%), and undocumented (40.4%). GPT-4o classification performance was strong (F1 > 0.71 across all categories), with the highest performance observed for statin intolerance (F1 = 0.96).

### Conclusions
GPT-4o can accurately identify clinical factors not captured in structured EHR data. This approach enables more accurate guideline-based quality assessments and yields actionable insights into reasons for apparent gaps in care.

Enhancing the Precision of Lipid Management Quality Assessment in ASCVD Using Large Language Models

### Objective
Multiple sclerosis (MS) is a chronic autoimmune disorder of the central nervous system frequently associated with visual symptoms. This study aimed to characterize the prevalence of ophthalmic conditions in individuals with MS and compare it to matched controls without MS.

### Methods
A matched case-control, cross-sectional study was conducted using data from the All of Us Research Program, a large, nationwide NIH-funded initiative. Individuals with MS (n = 3771) were matched 1:3 to controls without MS (n = 11,313) by age, sex, and race/ethnicity. Four ophthalmic conditions—optic neuritis, diplopia, nystagmus, and uveitis—were examined. Based on electronic health records, diagnosis dates were categorized into ophthalmic conditions occurring before, concurrently with, or after the MS diagnosis. Prevalence rates of ophthalmic conditions in individuals with MS were compared to those of matched controls, through univariate and multivariate logistic regression models, adjusting for sociodemographic factors, lifestyle variables, prior brain injury, family history of MS, and comorbidities.

### Results
All ophthalmic conditions were significantly more prevalent in individuals with MS than controls. Optic neuritis was most common (17.0 % vs. 0.2 %; adjusted odds ratio (aOR) = 31.96; 95 % CI: 22.09–48.20; p < 0.001), followed by diplopia (10.1 % vs. 1.0 %; aOR = 4.88; 95 % CI: 3.87–6.19; p < 0.001), uveitis (3.4 % vs. 0.7 %; aOR = 2.30; 95 % CI: 1.66–3.19; p < 0.001), and nystagmus (2.5 % vs. 0.2 %; aOR = 6.97; 95 % CI: 4.31–11.62; p < 0.001). The temporal analysis revealed that some cases of optic neuritis (31.9 %), nystagmus (21.9 %), diplopia (27.7 %), and uveitis (38.3 %) preceded MS diagnosis. Optic neuritis prior to MS was significantly more prevalent than matched controls (5.4 % vs. 0.2 %; aOR = 7.77; 95 % CI: 5.25, 11.94; p < 0.001).

### Conclusion
This study presents population-based data on the frequency of ophthalmic disease in patients with MS. Ophthalmic conditions, particularly optic neuritis, were significantly more common in individuals with MS compared to matched controls. The study also characterizes the prevalence of uveitis, which is relatively rarer than other ophthalmic conditions in the MS population, yet still more common than matched controls. Some visual conditions occurred before the clinical diagnosis of MS, some concurrently, and others afterward. These findings underscore the importance of recognizing visual disturbances in the diagnosis and management of MS and highlight the need for close collaboration between neurologists and ophthalmologists in the care of patients with MS.

Ophthalmic Conditions in Patients with Multiple Sclerosis

### Background
Idecabtagene vicleucel (ide-cel) is a B-cell maturation antigen (BCMA)-directed chimeric antigen receptor (CAR) T-cell therapy, it has emerged as a transformative treatment for relapsed/refractory multiple myeloma (R/RMM). On April 4, 2024, the U.S. Food and Drug Administration (FDA) approved ide-cel for adult patients with R/RMM who have received at least two prior lines of therapy, including an immunomodulatory agent, a proteasome inhibitor, and an anti-CD38 monoclonal antibody. This meta-analysis evaluates the efficacy and safety outcomes of ide-cel from current clinical evidence.

### Methods
A systematic search of Medline, Embase, Cochrane Library, Web of Science, and Scopus was conducted through July 2025 and supplemented with data from ClinicalTrials.gov. Five relevant clinical trials (n=730 patients) were included. We analyzed outcomes such as overall response rate (ORR), complete response (CR) rate, progression-free survival (PFS), and safety endpoints such as cytokine release syndrome (CRS), neurotoxicity, infections, and treatment-related mortality (TRM). Pooled estimates were calculated using weighted averages based on sample size.

### Results
The pooled ORR was 72.9%, with a CR or better rate of 30.2%. Median PFS across studies was 9.7 months. CRS occurred in 81.8% of patients, with grade ≥3 CRS in 3.7%. Neurotoxicity was reported in 27.1% of patients, including 4.6% with grade ≥3 events. Infections were noted in 44.8% of patients, and TRM was 5.5%, primarily due to infections or immune-mediated toxicity. CRS and neurotoxicity were largely early-onset and manageable with tocilizumab and corticosteroids. Toxicity incidence increased with higher CAR T-cell doses and advanced disease burden.

### Conclusion
Ide-cel demonstrates strong efficacy in heavily pretreated R/RMM patients, with high response rates and a median PFS approaching 10 months. The safety profile is characterized by frequent but manageable CRS and neurotoxicity, and infections remain a key consideration. These findings support ide-cel as a valuable treatment option in R/RMM, in line with its recent FDA approval. It is suggested to maintain ongoing monitoring and long-term follow-up to fully assess durability of benefit and late-onset toxicities or even second primary malignancies.

Efficacy and Safety of Idecabtagene Vicleucel in Relapsed/Refractory Multiple Myeloma

Background 
Chronic pain imposes a significant global burden, contributing to reduced quality of life and increased healthcare costs. Pain's multifaceted nature complicates the development of standardized treatment plans that meet diverse patient needs. Patients increasingly adopt complementary health approaches (CHAs), yet utilization patterns and clinical effects remain understudied. Recently acquired data were used to quantify the association between chronic pain and CHA utilization in U.S. adults, focusing on osteopathic manipulative treatment and other non-traditional modalities, and to determine whether any observed associations persist after adjusting for demographic factors. 
Methods 
Pre-existing data from a cross-sectional online survey of a representative sample of 3,022 U.S. adults were examined to identify patterns of CHA use among individuals diagnosed with chronic pain in the past year. Statistical analysis included Chi-Square tests of bivariate associations of chronic pain and types of CHA use. Logistic regression analyses, with and without adjustment for demographic variables, evaluated the clinical significance of these associations. CHAs were categorized into the five NIH-defined groups: Physical, Psychological, Nutritional, Combined, and System-Based, encompassing 30 distinct interventions. CHA usage, favorable expectation, and favorable experience of these modalities were analyzed. 
Results 
Individuals with chronic pain demonstrated significantly higher overall utilization of CHAs than those without (adjusted odds ratio = 2.36, 95% CI: 1.44–3.87). Osteopathic manipulative treatment (adjusted odds ratio = 3.29, 95% CI: 2.15–5.02) was among many CHA modalities more commonly used by these individuals. Although both groups had low expectancy for positive outcomes, those with chronic pain reported significantly lower expectations for various modalities, such as Any Nutritional CHA use, herbalist, non-RX diet, prayer, mindfulness, meditation, and yoga. Reported favorable experience for Any CHA use among those with chronic pain was 93.5%. Various Physical CHAs, acupuncture, and art, music, or dance therapy were reported to be high in both groups, but favorable experience was higher in chronic pain patients. 
Conclusion 
The preference for CHAs among chronic pain patients demonstrates the unmet needs in conventional care regarding symptom management, functional recovery, and mind-body interactions. While the cross-sectional design limits causal interpretation and self-reporting may introduce bias, these results support further longitudinal research to evaluate efficacy, drivers of utilization, and long-term outcomes.

The Association of Chronic Pain and Complementary Health Approach Usage: A Comprehensive Analysis Adjusting for Demographics

Background
Meniscus injuries are common with approximately 850,000 patients undergoing surgical treatment in the United States yearly. To investigate regenerative strategies for avascular meniscus tears, our lab has been utilizing bovine meniscus explants for investigating regenerative strategies for tears and crosstalk between joint tissues. However, inter-species crosstalk between bovine meniscus and human derived joint tissues remains a concern.

This study was designed to engineer and validate a model of human meniscus for engineered healing of avascular meniscus tears under the crosstalk between meniscus, synovial membrane, and IFP.

Methods
A wedge-shaped scaffold was 3D-printed with Ecoflex F Blend C1200 polymer. Synovial mesenchymal stem/progenitor cells (syMSCs) were isolated from surgically removed synovium of anonymous adult donors as per our previous methods. The scaffolds were then loaded with collagen bioink and 2,000,000 cell /mL syMSCs and then placed into the PDMS molds. Experiment 1: For the first 2 weeks, the tissue constructs were cultured in Fibrogenic induction supplemented (FIS) media with connective tissue growth factor (CTGF). For weeks 3-4, the tissue constructs were cultured in chondrogenic induction supplemented media (CIS) and transforming growth factor beta-3 (TGFβ-3). Experiment 2: For 4 weeks tissue constructs were cultured in FIS with CTGF and CIS with TGFβ-3. No loading was applied. Experiment 3: Tissue constructs were cultured in combined FIS (w/ CTGF) and CIS (w/ TGFβ-3) with no FBS and no loading.

Results
At 4 weeks, histology showed new tissue integration into the pores throughout the scaffolds. Picrosirius Red (PR) and Alcian Blue (AB) staining suggest the de novo tissues in the no loading group are dense fibrocartilaginous tissues. Polarized images of PR-stained section showed densely aligned collagen fibers, reminiscent of native meniscus, comprising circumferential fibers and radial tie fibers. Mechanical loading resulted in less mature fibrous tissue matrix with limited cartilaginous matrix. Combined culture with FIS (w/ CTGF) and CIS (w/ TGFβ-3) showed the most mature and dense fibrocartilage tissue development after 4 weeks. RNA sequencing data show similar expression levels of fibrochondrocyte-specific genes, including COL1A2, ACAN, COMP, and COL1A1, between engineered and native human meniscus tissue.



Conclusion
Our study suggests a reliable and effective approach to engineer human meniscus-like tissues that can serve as an experimental explant model for various types of meniscus explant research. Combined culture with FIS and CIS creates more mature fibrocartilage structure than step-wise differentiation under no physiological loading. These findings may have implications for engineering human meniscus-like tissue for various types of meniscus research.


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