Ande Xiaojie Marini

All Publications

• Stem cell-based therapies for treatment of abdominal aortic aneurysm: development, application, and future potential. npj biomedical innovations Badawy, S., Anand, S., Marini, A. X., Mulorz, J., Tsao, P. S., Huang, N. F. 2025; 2 (1): 41

  Abstract

  Abdominal aortic aneurysms (AAA), with approximately 200,000 new diagnoses each year, represent a prevalent clinical concern. Current treatment includes monitoring and surgical procedures once the aneurysm reaches a certain size. However, the lack of effective, timely therapies leads to a high mortality rate due to rupture. With recent advancements and innovations in biomedical science, stem cell therapy has moved closer to widespread clinical use, with the field experiencing rapid growth since its inception in the late 20th century. Given the pathophysiology of AAA, stem cell therapies have high potential impact in the treatment for both early and late-stage disease, targeting underlying mechanisms such as inflammation, vascular degeneration, and extracellular matrix degradation. There are many considerations and innovative potential approaches being explored in this type of treatment, such as strategically leveraging cell properties and their associated secretome and incorporating biomaterials-based strategies. This review article summarizes and critically assesses the efficacy of cell-based therapies in AAA preclinical models, current clinical trials in this area, and other emerging bioengineering approaches for the treatment of AAA.

  View details for DOI 10.1038/s44385-025-00044-8

  View details for PubMedID 41323882

  View details for PubMedCentralID PMC12657235

• "Attractive" Treatment for Abdominal Aortic Aneurysm Repair: Magnetic Localization of Silk-Iron Packaged Extracellular Vesicles JOURNAL OF FUNCTIONAL BIOMATERIALS Marini, A. X., Mcloughlin, K. J., Pellegrino, A. R., Tomaraei, G. N., Li, B., Curci, J. A., Bedewy, M., Weinbaum, J. S., Vorp, D. A. 2025; 16 (11)

  Abstract

  Abdominal aortic aneurysm (AAA) is a dilatation of the distal aorta to a diameter of 50% or more of its normal size of about 2 cm. Risk of aortic rupture can be nearly eliminated with either open surgery or endovascular repair. Procedural risks limit the value of these interventions unless the diameter of the aneurysm has reached a critical threshold (established as 5.5 cm in men or 5.0 cm in women). Thus, patients are monitored until this threshold is reached. Approximately 80% of small AAA will grow and exceed the threshold, providing a therapeutic window for altering this natural history and reducing the risk of rupture. Previous work in our lab has utilized adipose-derived mesenchymal stem cells (ASCs) to treat AAA in vivo, preserving elastic fibers and slowing aneurysm expansion. This work sought to create a delivery system for therapeutic extracellular vesicles (ASC-EVs) secreted by ASCs. Our delivery system incorporated the biocompatibility of regenerated silk fibroin (RSF), the magnetic moveability of iron oxide nanoparticles (IONPs), and the regenerative nature of ASC-EVs to create silk-iron packaged extracellular vesicles (SIPEs). Using this system, we tested the ability to magnetically localize the SIPEs and release their encapsulated ASC-EVs to exert their regenerative effects in vitro. We were successful in magnetically localizing the SIPEs in vitro and silk-iron microparticles (SIMPs) in vivo and in detecting their releasates via flow cytometry and cellular uptake assays. However, while their releasates were detected, their biological effects were diminished compared to unencapsulated controls. Thus, additional optimization related to loading efficiency is needed.

  View details for DOI 10.3390/jfb16110395

  View details for Web of Science ID 001623846900001

  View details for PubMedID 41295051

  View details for PubMedCentralID PMC12653497

• Chemical Conjugation of Iron Oxide Nanoparticles for the Development of Magnetically Directable Silk Particles ACS APPLIED MATERIALS & INTERFACES Marini, A. X., Tomaraei, G. N., Weinbaum, J. S., Bedewy, M., Vorp, D. A. 2025; 17 (6): 8901-8913

  Abstract

  Magnetically directable materials containing iron oxide nanoparticles (IONPs) have been utilized for a variety of medical applications, including localized drug delivery. Regenerated silk fibroin (RSF) has also been used in numerous regenerative medicine and drug delivery applications, given its biocompatibility and tunable properties. In this work, we explored the hypothesis that chemically conjugating IONPs to RSF to anchor the IONPs to silk microparticles would provide better magnetic guidance than nonconjugated IONPs untethered to silk microparticles. IONPs were fabricated using a coprecipitation method and conjugated with glutathione (GSH) prior to mixing with RSF. IONPs incorporated into RSF were mixed with potassium phosphate buffer to fabricate microparticles. IONPs with and without GSH were characterized for particle size, shape, morphology, GSH conjugation efficiency, and composition. Silk iron microparticles (SIMPs) were also characterized for particle size, shape, and composition and tested for stability, degradation properties, magnetic movability, and cytotoxicity. IONPs demonstrated a uniform size distribution and spherical morphology. Conjugation of IONPs with GSH was verified through changes in the X-ray photoelectron spectroscopy (XPS) and Fourier-transform infrared spectroscopy (FTIR) spectra. IONPs and RSF were able to be chemically conjugated and fabricated into SIMPs, which demonstrated a spherical and porous morphology. FTIR revealed an increased β-sheet content in SIMPs, suggesting that the IONPs may be inducing conformational changes in the silk fibroin. SIMPs showed stability up to 4 weeks in ultrapure water and rapid enzymatic degradation within 24 h. SIMPs were able to be moved magnetically through solution and through a hydrogel and were not cytotoxic.

  View details for DOI 10.1021/acsami.4c17536

  View details for Web of Science ID 001413288200001

  View details for PubMedID 39900356

  View details for PubMedCentralID PMC11826889

• Mesenchymal Stem Cell-Conditioned Media-Loaded Microparticles Enhance Acute Patency in Silk-Based Vascular Grafts BIOENGINEERING-BASEL Lorentz, K. L., Marini, A. X., Bruk, L. A., Gupta, P., Mandal, B. B., Dileo, M. V., Weinbaum, J. S., Little, S. R., Vorp, D. A. 2024; 11 (9)

  Abstract

  Coronary artery disease leads to over 360,000 deaths annually in the United States, and off-the-shelf bypass graft options are currently limited and/or have high failure rates. Tissue-engineered vascular grafts (TEVGs) present an attractive option, though the promising mesenchymal stem cell (MSC)-based implants face uncertain regulatory pathways. In this study, "artificial MSCs" (ArtMSCs) were fabricated by encapsulating MSC-conditioned media (CM) in poly(lactic-co-glycolic acid) microparticles. ArtMSCs and control microparticles (Blank-MPs) were incubated over 7 days to assess the release of total protein and the vascular endothelial growth factor (VEGF-A); releasates were also assessed for cytotoxicity and promotion of smooth muscle cell (SMC) proliferation. Each MP type was loaded in previously published "lyogel" silk scaffolds and implanted as interposition grafts in Lewis rats for 1 or 8 weeks. Explanted grafts were assessed for patency and cell content. ArtMSCs had a burst release of protein and VEGF-A. CM increased proliferation in SMCs, but not after encapsulation. TEVG explants after 1 week had significantly higher patency rates with ArtMSCs compared to Blank-MPs, but similar to unseeded lyogel grafts. ArtMSC explants had lower numbers of infiltrating macrophages compared to Blank-MP explants, suggesting a modulation of inflammatory response by the ArtMSCs. TEVG explants after 8 weeks showed no significant difference in patency among the three groups. The ArtMSC explants showed higher numbers of SMCs and endothelial cells within the neotissue layer of the graft compared to Blank-MP explants. In sum, while the ArtMSCs had positive effects acutely, efficacy was lost in the longer term; therefore, further optimization is needed.

  View details for DOI 10.3390/bioengineering11090947

  View details for Web of Science ID 001324046900001

  View details for PubMedID 39329689

  View details for PubMedCentralID PMC11428691