Stanford Fan Yang Lab
Research
Our research leverages biomaterials to improve the human healthspan and lifespan through regenerative medicine and develop high-fidelity 3D models to facilitate therapeutic discovery. Our work sits the intersection of biomaterials innovation, clinical application, and biological discovery. We leverage engineered tools not only to address unmet clinical needs but also to uncover the fundamental biological mechanisms governing tissue regeneration and disease progression.
We have established three high-impact, interdisciplinary research themes that define the current and future directions of our team. These themes, as detailed below, represent a significant expansion in the scope and impact of our research, providing a robust framework for long-term impact. Hover over each topic to reveal details!
Immunomodulation
Immune cells are the first responders to tissue injury, and they secrete paracrine signals to recruit additional cell types for healing. Increasing evidence suggests that biomaterials can improve soft tissue regeneration via immunomodulation, however, the effect of biomaterials on immune cell response in tissue regeneration remains understudied.
Our lab's unique microribbon (µRB) scaffolds feature an inherent interconnected macroporosity and ribbon-like morphology, making them ideal for recruiting host immune cells. By tuning µRB composition and surface modification, we create instructive scaffolds that induce pro-regenerative responses from key immune populations, including macrophages and T-cells.
Representative publications:
Su et al., Modulating immune-stem cell crosstalk enables robust bone regeneration via tuning compositions of macroporous scaffolds. NPJ Regen Med, 2025. Link
Su et al., Stem Cell Membrane-Coated Microribbon Scaffolds Induce Regenerative Innate and Adaptive Immune Responses in a Critical-Size Cranial Bone Defect Model. Adv Materials, 2023. Link
Mechanobiology
Recent advances in mechanobiology have underscored the importance of extracellular matrix mechanical cues in guiding cell fates in 3D. However, most studies have focused on bulk mechanical properties, which can differ markedly from the local mechanical cues that cells experience at the microscale.
To bridge this gap, our lab has developed sliding hydrogels (SG) with mobile crosslinks and ligands to control and elucidate how local matrix mechanics dictate cell fates in 3D in the context of cartilage regeneration and degeneration. We have also developed viscoelastic, brain-mimicking hydrogels that demonstrate the critical role of tumor mechanics in driving glioblastoma invasiveness and resistance. These platforms have enabled us to study targeting mechanosensing as a novel therapeutic strategy for treating degenerative joint diseases and aggressive cancers.
Representative publications:
Ayushman et al., Cell tumbling enhances stem cell differentiation in hydrogels via nuclear mechanotransduction. Nature Materials 2024. Link
Sinha et al., Matrix Stiffness Regulates GBM Migration and Chemoradiotherapy Responses via Chromatin Condensation in 3D Viscoelastic Matrices. ACS Appl Mater Interfaces 2025. Link
Schematic of our spatially patterned 3D bone metastasis model, allowing for the study of cancer cell invasion at the bone marrow/bone tissue interface.
Representative publications:
González Díaz et al., Spatially patterned 3D model mimics key features of cancer metastasis to bone. Biomaterials 2023. Link
González Díaz et al., A 3D Osteosarcoma Model with Bone-Mimicking Cues Reveals a Critical Role of Bone Mineral and Informs Drug Discovery. Adv Healthc Mater. 2022. Link
In vitro disease modeling
While the genetic drivers of cancer have been extensively studied, how cell-matrix and cell-cell interactions drive cancer progression and therapeutic resistance remain understudied. We have developed 3D in vitro disease models to mimic brain cancer (glioblastoma) and bone cancers (osteosarcoma and brain metastasis). These models bridge the gap between conventional 2D models and animal models by better mimicking the tumor ECM as well as human cancer cell-stromal cell interactions. Utilizing these 3D in vitro cancer models for mechanistic studies, we identify key drivers of cancer invasiveness and therapeutic resistance and enable drug screening with substantially reduced time and cost.
Featured Material Platforms
Microribbon hydrogels
Conventional hydrogels are often nanoporous, lacking the macroporosity desirable for cell and tissue growth, and exhibit poor mechanical properties when subject to mechanical loading.
Our patented µRB-based hydrogel technology was specifically designed to overcome these limitations by combining injectability, macroporosity, and shock-absorbing mechanical properties. You can think of these µRBs like Legos: each piece features tunable biochemical and mechanical properties, and they can be easily mixed and matched through compatible crosslinking chemistries to promote desirable cell fates and tissue responses. We can also incorporate nanoparticles into the µRB scaffold to enable tunable in situ release of soluble factors.
Wet-spinning gelatin solution into fibers
Highlighted publications:
Sliding hydrogels
Depending on the crosslinking mechanism, hydrogels can be broadly divided into two categories: physically-crosslinked hydrogels or covalently crosslinked hydrogels. Physical hydrogels are highly mobile but lack stability, and covalently crosslinked hydrogels are stable but do not offer any molecular mobility. How molecular mobility modulates cell fates in 3D remains unknown due to the lack of biomaterial tools to interrogate such questions.
To fill in these gaps of knowledge, our lab has recently reported the sliding hydrogel as a 3D stem cell niche, which exhibits stability comparable to that of chemical hydrogels, yet allows tunable molecular mobility with crosslinks and biochemical ligands linked to mobile sliding rings. The molecular mobility of this hydrogel allows stem cells to reorganize their surrounding ligands in 3D, supporting efficient stem cell differentiation toward various lineages.
Mesenchymal stem cells "dancing" in a sliding hydrogel
Highlighted publications:
Spatial patterning and biofabrication
Uniform biomaterials cannot mimic the anisotropic nature of native tissues or disease behavior at interfaces. Our lab is interested in regenerating tissues with zonal organization (cartilage) and studying interfaces (bone-tendon or bone-cancer), and we have developed various hydrogel platforms with unique structures to meet these needs. These include aligned scaffolds to improve chondrogenesis, gradient stiffness and niche cues, and spatially patterned cancer metastasis models.
Recently, we have integrated 3D bioprinting with our microribbon hydrogel platform to improve throughput in our 3D disease models, regenerate anisotropic tissues, and enhance immunomodulation.
Spatially patterned bioprint demonstration
Highlighted publications: