About

Sarah Heilshorn is the Rickey/Nielsen Professor in the School of Engineering at Stanford University. She also holds courtesy professorships in Bioengineering and Chemical Engineering. Her professional biography on the Stanford Materials Science and Engineering faculty page identifies her as the Department Chair. The page lists her among other faculty members but does not provide further details about her research focus, background, or key contributions.

Research topics

• Computer Science
• Biology
• Materials science
• Medicine
• Nanotechnology
• Pathology
• Biomedical engineering
• Cell biology
• Neuroscience
• Chemistry
• Mathematical analysis
• Physical chemistry
• Physics
• Bioinformatics
• Classical mechanics
• Genetics
• Computational biology
• Optics
• Mathematics
• Quantum mechanics
• Engineering
• Composite material
• Anatomy
• Polymer chemistry

Selected publications

• Physiological Buffer Selection Alters the Mechanics of Hydrogels with Hydrazone Cross-Links

  Biomacromolecules · 2026-04-28

  articleSenior authorCorresponding

  Hydrogels are used for a wide range of biomedical applications. While mechanical characterization of hydrogels is frequently performed in isotonic saline, the chemical identity of these solutions may vary widely from the ionic environments encountered during their use. To explore this idea, we test the mechanical properties of a hydrogel cross-linked with dynamic covalent chemistry (DCC) in several physiologically relevant ionic solutions that mimic different biological conditions. Specifically, we evaluate rheological properties of a hydrazone-cross-linked hydrogel composed of recombinant, chemically modified hyaluronan and elastin-like protein (ELP). Our results show that the shear moduli and stress relaxation properties of DCC hydrogels can vary significantly in different ionic environments. We identify the thermoresponsive nature of ELP and changes in hydrazone bond kinetics as the primary reasons for the observed differences in mechanical properties. Taken together, this work elucidates mechanisms underpinning changes in hydrogel mechanics in different physiological solutions.

  PublisherDOI

• Viscoelastic N‑cadherin-like interactions maintain neural progenitor cell stemness within 3D matrices

  Nature Communications · 2025-06-05 · 11 citations

  articleOpen accessSenior author

  Neural progenitor cells (NPCs) hold immense potential as therapeutic candidates for neural regeneration, and materials-based strategies have emerged as attractive options for NPC expansion. However, maintaining NPC stemness has proven challenging in vitro, due to their propensity to form cell-dense neurospheres. While neurospheres promote cell–cell interactions required for NPC stem maintenance, they also restrict oxygen transport, leading to hypoxia and limited cell expansion. To overcome these limitations, we investigate two materials-based approaches to maintain NPC stemness: 1) physical matrix remodeling within a viscoelastic, stress-relaxing hydrogel and 2) matrix-induced N-cadherin-like signaling through a cell-instructive peptide. While viscoelasticity alone is sufficient to maintain NPC stemness compared to an elastic environment, NPCs still preferentially form neurospheres. The addition of N-cadherin-like peptides promotes a distributed culture of NPCs while maintaining their stemness through cadherin-mediated signaling, ultimately exhibiting improved long-term expansion and neural differentiation. Thus, our findings reveal matrix viscoelasticity and engineered N-cadherin-like interactions as having a synergistic effect on NPC expansion and differentiation within 3D matrices. Maintaining neural progenitor cell stemness has proven challenging in vitro, due to their propensity to form cell-dense neurospheres. Here, the authors developed a 3D hydrogel system that supports neural progenitor cell stemness maintenance and differentiation by tuning matrix mechanics and cell-binding cues, enabling long-term expansion and neuron formation without needing dense cell clusters.

  PublisherOA PDFDOI

• Crosslink strength governs yielding behavior in dynamically crosslinked hydrogels

  Biomaterials Science · 2025-01-01 · 7 citations

  articleOpen access

  Yielding of dynamically crosslinked hydrogels, or the transition between a solid-like and liquid-like state, allows facile injection and utility in translational biomedical applications including delivery of therapeutic cells. Unfortunately, the time-varying nature of the transition is not well understood, nor are there design rules for understanding the effects of yielding on encapsulated cells. Here, we unveil underlying molecular mechanisms governing the yielding transition of dynamically crosslinked gels currently being researched for use in cell therapy. We demonstrate through nonlinear rheological characterization that the network dynamics of the dynamic hydrogels dictate the speed and character of their yielding transition. Rheological testing of these materials reveals unexpected elastic strain stiffening during yielding, as well as characterization of the rapidity of the yielding transition. A slower yielding speed explains enhanced protection of directly injected cells from shear forces, highlighting the importance of mechanical characterization of all phases of yield-stress biomaterials.

  PublisherOA PDFDOI

• Dual-orientation of collagen fibers to guide cell alignment in 3D-printed constructs

  Acta Biomaterialia · 2025-11-13 · 1 citations

  articleSenior authorCorresponding
  PublisherDOI

• Submucosal Hydrogel for Spring‐Mediated Intestinal Lengthening

  Journal of Biomedical Materials Research Part A · 2025-09-22

  article

  Spring-mediated distraction enterogenesis has shown success in intestinal lengthening, with spring confinement achieved by external plication with sutures to reduce the lumen diameter at both ends of the intestinal segment. Endoscopic spring placement would minimize the morbidity associated with device insertion. This study investigates the use of submucosal injection of engineered hydrogel to temporarily confine a compressed spring within an intestinal segment. Engineered hydrogels were composed of hyaluronic acid (HA) alone or HA with elastin-like protein (HELP). To simulate endoscopic injection in six juvenile pigs, hydrogel was injected into the submucosa in everted jejunum, followed by the placement of a gelatin-encapsulated, compressed nitinol spring. The jejunum was then unfolded over the spring, and hydrogel was injected distally into the submucosa. Sutures were placed as fiducial markers. After 7 days on a liquid diet, the pigs were euthanized, and their intestinal segments were analyzed for lengthening and histological changes. The spring-containing jejunal segments expanded in all animals, lengthening to 132% in the HA group and 188% in the HELP group. HELP hydrogels exhibited slower biodegradation than HA-only hydrogels. Histological analysis showed increased crypt width and decreased crypt density in the spring-containing segments compared to controls. Hydrogel effectively provides temporary spring confinement within intestinal segments without adverse effects. The mechanical stimulation from the spring induces crypt fission, expanding the intestinal epithelium. These results support the feasibility of gel-enabled, spring-mediated distraction enterogenesis for intestinal lengthening.

  PublisherDOI

• Targeting Cell‐Matrix Induced Chemoresistance With Regorafenib in a <scp>3D</scp> Model of Osteosarcoma

  Journal of Biomedical Materials Research Part A · 2025-09-01 · 1 citations

  articleOpen accessSenior authorCorresponding

  Over the past four decades, there has been little advancement in treatment strategies for osteosarcoma (OS), the predominant primary bone tumor in the pediatric patient population. Current therapy involves multiple rounds of chemotherapy and surgical resection, which are associated with significant morbidity and suboptimal survival rates. A key challenge in developing new treatments is the difficulty in replicating the OS tumor microenvironment, particularly cell interactions with the extracellular matrix (ECM). This study uses an in vitro model of OS to investigate the cell response to collagen (COL) type I, the primary component of the OS ECM. After 7 days of culture within three-dimensional COL hydrogels, OS cells displayed a more elongated cellular morphology and reduced sensitivity to the standard chemotherapy used for OS treatment compared to cells grown on two-dimensional substrates. To test whether this model could be used to study treatment strategies used for high-risk OS patients, we applied a metronomic regimen combining regorafenib, a multi-tyrosine kinase inhibitor, with front-line chemotherapy to overcome cell-matrix induced chemoresistance. We identified overexpression of the ATP-binding cassette transporter ABCG2, a drug efflux pump, as a potential mechanism of resistance in 3D culture. Regorafenib's inhibitory effect on ABCG2 suggests a mechanistic basis for its ability to restore chemosensitivity in 3D culture. Altogether, these findings highlight the importance of cell-matrix interactions in in vitro OS models, provide valuable insights into a matrix-induced mechanism of OS chemoresistance, and suggest an approach to its treatment.

  PublisherOA PDFDOI

• Expanding the Versatility of Dynamic Covalent Hydrogels with Static Covalent Spot-Welding

  Chemistry of Materials · 2025-12-11 · 2 citations

  articleSenior authorCorresponding

  Hydrogels cross-linked through dynamic covalent chemistry (DCC) can mimic the viscoelastic properties of native biological tissues; however, these materials often suffer from rapid erosion, greatly limiting their application in biological studies. To address this challenge, we developed a DCC hydrogel with enhanced stability by sparsely distributing static covalent bonds, termed “spot-welds,” throughout the network. These spot-welds served as anchor points to prevent polymer erosion and significantly improved gel stability without compromising viscoelasticity. Specifically, our single-network system (termed HELP) consisted of two recombinant biopolymers, hyaluronic acid (HA) and an engineered elastin-like protein (ELP), each modified to cross-link through both dynamic hydrazone bonds and static strain-promoted azide–alkyne cycloaddition (SPAAC) bonds. Gels with and without sparsely distributed spot-welds had similar stiffness (G′ ∼ 800 Pa), stress relaxation rates (τ1/2 ∼ 6000 s), and shear-thinning behavior, resulting in gels that were viscoelastic and extrudable through a 3D printing syringe. Importantly, the spot-welds significantly improved gel stability, with DCC-only gels suffering complete erosion by day 4, while spot-welded gels remained stable for at least 14 days. This combination of enhanced gel stability with viscoelastic mechanics enabled the 3D culture and maturation of human stem cell-derived cardiomyocytes. While elastic control gels resulted in loss of cardiomyocyte phenotype, the spot-welded viscoelastic gels supported cardiomyocyte spreading, spontaneous beating, and expression of α-actinin and troponin T. In summary, sparsely distributing static cross-links on each biopolymer within a dynamic covalent network results in an injectable and printable single-network hydrogel with viscoelastic mechanics and significantly enhanced stability, supporting 3D cardiomyocyte culture and maturation.

  PublisherDOI

• One-step bioprinting of endothelialized, self-supporting arterial and venous networks

  Biofabrication · 2025-01-16 · 7 citations

  articleOpen accessSenior author

  Advances in biofabrication have enabled the generation of freeform perfusable networks mimicking vasculature. However, key challenges remain in the effective endothelialization of these complex, vascular-like networks, including cell uniformity, seeding efficiency, and the ability to pattern multiple cell types. To overcome these challenges, we present an integrated fabrication and endothelialization strategy to directly generate branched, endothelial cell-lined networks using a diffusion-based, embedded 3D bioprinting process. In this strategy, a gelatin microparticle sacrificial ink delivering both cells and crosslinkers is extruded into a crosslinkable gel precursor support bath. A self-supporting, perfusable structure is formed by diffusion-induced crosslinking, after which the sacrificial ink is melted to allow cell release and adhesion to the printed lumen. This approach produces a uniform cell lining throughout networks with complex branching geometries, which are challenging to uniformly and efficiently endothelialize using conventional perfusion-based approaches. Furthermore, the biofabrication process enables high cell viability (>90%) and the formation of a confluent endothelial layer providing vascular-mimetic barrier function and shear stress response. Leveraging this strategy, we demonstrate for the first time the patterning of multiple endothelial cell types, including arterial and venous cells, within a single arterial-venous-like network. Altogether, this strategy enables the fabrication of multi-cellular engineered vasculature with enhanced geometric complexity and phenotypic heterogeneity.

  PublisherOA PDFDOI

• Osteopontin attenuates the foreign-body response to silicone implants

  Nature Biomedical Engineering · 2025-03-24 · 9 citations

  articleOpen access
  PublisherOA PDFDOI

• Interpenetrating networks of fibrillar and amorphous collagen promote cell spreading and hydrogel stability

  Acta Biomaterialia · 2025-01-09 · 22 citations

  articleOpen accessSenior authorCorresponding
  PublisherOA PDFDOI

Recent grants

• NIH Grant DP2OD00647701

  NIH · $2.4M · 2014

• Engineered matrix microarrays to enhance the regenerative potential of iPSC-derived endothelial cells

  NIH · $1.6M · 2018–2024

• Injectable Hydrogels to Protect Transplanted Cells from Hypoxia

  NIH · $1.1M · 2019–2023

• NIH Grant R21EB020235

  NIH · $189k · 2018

• NIH Grant R21HL138042

  NIH · $435k · 2021

Frequent coauthors

• Howard J. Lim

  1600 shared

• Kohei Tabuchi

  Kobe University

  1600 shared

• Andrew J. deMello

  Institute for Biomedical Engineering

  1600 shared

• Paulette Clancy

  Johns Hopkins University

  1600 shared

• Helena S. Azevedo

  i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto

  1600 shared

• Yuki Nakanishi

  Royal Society of Chemistry

  1600 shared

• Xuefeng Guo

  Peking University

  1600 shared

• Sean Browner

  ETH Zurich

  1600 shared

Education

• Ph.D., Materials Science and Engineering

  Stanford University

  2006

• B.S., Materials Science and Engineering

  Massachusetts Institute of Technology

  2001