Michelle Tai

All Publications

• Impact of Scaffold Material Choice on Osteosarcoma Phenotype and Drug Responses in 3D. Acta biomaterialia Monette, C. E., Lee, J., Peasah, A., Sayles, L., Tai, M., Sweet-Cordero, A., Yang, F. 2025

  Abstract

  Biomaterials-based 3D models have emerged as new cancer research tools for studying osteosarcoma (OS). However, the impact of scaffold material choice on OS phenotype and drug responses in 3D remains largely unknown, as previous studies used different biomaterials as scaffolds without direct comparison. In this study, we systematically compared four biomaterials: Gelatin methacrylate (GelMA), Gelatin microribbons (Gel µRB), Collagen I hydrogel (Col1), and Poly(DL-lactide-co-glycolide) (PLGA). All have previously been applied for either 3D OS culture or bone tissue engineering. To mimic the mineral component of bone, hydroxyapatite mineral nanoparticles (HAnp) were incorporated into all scaffolds. We assessed key clinically relevant OS phenotypes including cell proliferation, extracellular matrix (ECM) deposition, and responses to multiple chemotherapeutic agents. Our results demonstrate that scaffold material significantly influences OS phenotype and drug resistance. Notably, PLGA results in the lowest cell proliferation, GelMA promotes drug resistance and tumor ECM deposition, and Gel µRB better mimics OS signaling of orthotopic tumor xenografts in vivo. The findings from this comparative study underscores the impact of scaffold choice on OS phenotype and drug response. It also provides valuable insights to help guide the selection of appropriate scaffold materials to better mimic the desirable OS phenotype to advance OS therapeutic discovery. STATEMENT OF SIGNIFICANCE: Osteosarcoma (OS), a highly aggressive bone cancer, has seen a stagnant survival rate for over three decades. This study addresses a critical knowledge gap by comparing four widely used bone tissue engineering scaffolds for 3D OS culture. Unlike previous studies, this work provides a comprehensive analysis of how scaffold choice influences OS proliferation, signaling, extracellular matrix deposition, and drug resistance. These findings underscore the critical role of biomaterials choice in modulating OS behavior and will guide the choice of 3D scaffolds for more effective OS disease modeling and improving therapeutic discovery.

  View details for DOI 10.1016/j.actbio.2025.08.046

  View details for PubMedID 40882907

• Donor Variability and 3D Culture Models Influence Human Mesenchymal Stem Cell Differentiation. Tissue engineering. Part A Jones, S., Tai, M., Ayushman, M., Peasah, A., Johannsen, J., Yang, F. 2025

  Abstract

  Mesenchymal stem cells (MSCs) are widely used for tissue regeneration due to their multilineage differentiation potential and ability to secrete paracrine factors with immunomodulatory and angiogenic functions. Standard MSC differentiation protocols typically rely on two-dimensional (2D) or pellet culture models that are simple to use but not well-suited for translational or clinical applications. To promote better cell survival, tissue deposition, and differentiation of MSCs, a wide variety of three-dimensional (3D) biomaterial scaffolds and platforms have been developed that provide structural support and present a carefully defined set of biochemical and biophysical cues to cells. While biomaterials can guide cell behavior and promote desirable tissue regeneration outcomes, one remaining challenge in the field is inherent donor-to-donor variability in MSC behavior, phenotype, and differentiation capacity. Although MSCs are promising tools for regeneration, the influence of donor variability on MSC differentiation across culture models remains poorly understood. Previous studies typically use cells from a single donor or rely solely on standard culture models. To address these gaps, we compared MSCs from six human donors and assessed differentiation across chondrogenic, osteogenic, and adipogenic lineages using both standard (pellet or 2D) and 3D biomaterial-based culture models. Alginate hydrogels were used to assess chondrogenesis, while gelatin microribbon (RB) hydrogels were used to evaluate osteogenesis and adipogenesis in 3D. Significant donor-to-donor variability was observed in differentiation outcomes across all three lineages and within both 2D and 3D culture models. By directly comparing donor variability in 2D and 3D, we provide evidence that standard 2D models cannot predict MSC differentiation capacity in 3D biomaterials. Therefore, to improve therapeutic efficacy and advance biomaterial-based strategies for tissue regeneration, it is critical to understand how donor variability affects MSC differentiation patterns across 3D biomaterial-based culture models.

  View details for DOI 10.1089/ten.tea.2025.0028

  View details for PubMedID 40407303

• Incorporating Bone-Derived ECM into Macroporous Microribbon Scaffolds Accelerates Bone Regeneration. Advanced healthcare materials Villicana, C., Su, N., Yang, A., Tong, X., Lee, H. P., Ayushman, M., Lee, J., Tai, M., Kim, T., Yang, F. 2025: e2402138

  Abstract

  Tissue-derived extracellular matrix (tdECM) hydrogels serve as effective scaffolds for tissue regeneration by promoting a regenerative immune response. While most tdECM hydrogels are nanoporous and tailored for soft tissue, macroporosity is crucial for bone regeneration. Yet, there's a shortage of macroporous ECM-based hydrogels for this purpose. The study aims to address this gap by developing a co-spinning technique to integrate bone-derived ECM (bECM) into gelatin-based, macroporous microribbon (µRB) scaffolds. The effect of varying doses of bECM on scaffold properties was characterized. In vitro studies revealed 15% bECM as optimal for promoting MSC osteogenesis and macrophage (Mφ) polarization. When implanted in a mouse critical-sized cranial bone defect model, 15% bECM with tricalcium phosphate (TCP) microparticles significantly accelerated bone regeneration and vascularization, filling over 55% of the void by week 2. Increasing bECM to 25% enhanced mesenchymal stem cell (MSC) recruitment and decreased M1 Mφ polarization but reduced overall bone formation and vascularization. The findings demonstrate co-spun gelatin/bECM hydrogels as promising macroporous scaffolds for robust endogenous bone regeneration, without the need for exogenous cells or growth factors. While this study focused on bone regeneration, this platform holds the potential for incorporating various tdECM into macroporous scaffolds for diverse tissue regeneration applications.

  View details for DOI 10.1002/adhm.202402138

  View details for PubMedID 39891301

• Spatially patterned 3D model mimics key features of cancer metastasis to bone. Biomaterials González Díaz, E. C., Tai, M., Monette, C. E., Wu, J. Y., Yang, F. 2023; 299: 122163

  Abstract

  Bone is the most common target of metastasis in breast cancer and prostate cancer, leading to significant mortality due to lack of effective treatments. The discovery of novel therapies has been hampered by a lack of physiologically relevant in vitro models that can mimic key clinical features of bone metastases. To fill this critical gap, here we report spatially patterned, tissue engineered 3D models of breast cancer and prostate cancer bone metastasis which mimic bone-specific invasion, cancer aggressiveness, cancer-induced dysregulation of bone remodeling, and in vivo drug response. We demonstrate the potential of integrating such 3D models with single-cell RNA sequencing to identify key signaling drivers of cancer metastasis to bone. Together, these results validate that spatially patterned 3D bone metastasis models mimic key clinical features of bone metastasis and can serve as a novel research tool to elucidate bone metastasis biology and expedite drug discovery.

  View details for DOI 10.1016/j.biomaterials.2023.122163

  View details for PubMedID 37236137