Dry and wet wrinkling of a silk fibroin biopolymer by a shape-memory material with insight into mechanical effects on secondary structures in the silk network.

Surface wrinkling provides an approach to modify the surfaces of biomedical devices to better mimic features of the extracellular matrix and guide cell attachment, proliferation, and differentiation. Biopolymer wrinkling on active materials holds promise but is poorly explored. Here we report a mechanically actuated assembly process to generate uniaxial micro-and nanosized silk fibroin (SF) wrinkles on a thermo-responsive shape-memory polymer (SMP) substrate, with wrinkling demonstrated under both dry and hydrated (cell compatible) conditions. By systematically investigating the influence of SMP programmed strain magnitude, film thickness, and aqueous media on wrinkle stability and morphology, we reveal how to control the wrinkle sizes on the micron and sub-micron length scale. Furthermore, as a parameter fundamental to SMPs, we demonstrate that the temperature during the recovery process can also affect the wrinkle characteristics and the secondary structures in the silk network. We find that with increasing SMP programmed strain magnitude, silk wrinkled topographies with increasing wavelengths and amplitudes are achieved. Furthermore, silk wrinkling is found to increase ß-sheet content, with spectroscopic analysis suggesting that the effect may be due primarily to tensile (e.g., Poisson effect and high-curvature wrinkle) loading modes in the SF, despite the compressive bulk deformation (uniaxial contraction) used to produce wrinkles. Silk wrinkles fabricated from sufficiently thick films (roughly 250 nm) persist after 24 h in cell culture medium. Using a fibroblast cell line, analysis of cellular response to the wrinkled topographies reveals high viability and attachment. These findings demonstrate use of wrinkled SF films under physiologically relevant conditions and suggest the potential for biopolymer wrinkles on biomaterials surfaces to find application in cell mechanobiology, wound healing, and tissue engineering.

Tuning the Topography of Dynamic 3D Scaffolds through Functional Protein Wrinkled Coatings.

Surface wrinkling provides an approach to fabricate micron and sub-micron-level biomaterial topographies that can mimic features of the dynamic, in vivo cell environment and guide cell adhesion, alignment, and differentiation. Most wrinkling research to date has used planar, two-dimensional (2D) substrates, and wrinkling work on three-dimensional (3D) structures has been limited. To enable wrinkle formation on architecturally complex, biomimetic 3D structures, here, we report a simple, low-cost experimental wrinkling approach that combines natural silk fibroin films with a recently developed advanced manufacturing technique for programming strain in complex 3D shape-memory polymer (SMP) scaffolds. By systematically investigating the influence of SMP programmed strain magnitude, silk film thickness, and aqueous media on wrinkle morphology and stability, we reveal how to generate and tune silk wrinkles on the micron and sub-micron scale. We find that increasing SMP programmed strain magnitude increases wavelength and decreases amplitudes of silk wrinkled topographies, while increasing silk film thickness increases wavelength and amplitude. Silk wrinkles persist after 24 h in cell culture medium. Wrinkled topographies demonstrate high cell viability and attachment. These findings suggest the potential for fabricating biomimetic cellular microenvironments that can advance understanding and control of cell-material interactions in engineering tissue constructs.

Thermally and Photothermally Triggered Cytocompatible Triple-Shape-Memory Polymer Based on a Graphene Oxide-Containing Poly(ε-caprolactone) and Acrylate Composite.

Triple-shape-memory polymers (triple-SMPs) are a class of polymers capable of fixing two temporary shapes and recovering sequentially from the first temporary shape to the second temporary shape and, last, to the permanent shape. To accomplish a sequential shape change, a triple-SMP must have two separate shape-fixing mechanisms triggerable by distinct stimuli. Despite the biomedical potential of triple-SMPs, a triple-SMP that with cells present can undergo two different shape changes via two distinct cytocompatible triggers has not previously been demonstrated. Here, we report the design and characterization of a cytocompatible triple-SMP material that responds separately to thermal and light triggers to undergo two distinct shape changes under cytocompatible conditions. Tandem triggering was achieved via a photothermally triggered component, comprising poly(ε-caprolactone) (PCL) fibers with graphene oxide (GO) particles physically attached, embedded in a thermally triggered component, comprising a tert-butyl acrylate-butyl acrylate (tBA-BA) matrix. The material was characterized in terms of thermal properties, surface morphology, shape-memory performance, and cytocompatibility during shape change. Collectively, the results demonstrate cytocompatible triple-shape behavior with a relatively larger thermal shape change (an average of 20.4 ± 4.2% strain recovered for all PCL-containing groups) followed by a smaller photothermal shape change (an average of 3.5 ± 0.8% strain recovered for all PCL-GO-containing groups; samples without GO showed no recovery) with greater than 95% cell viability on the triple-SMP materials, establishing the feasibility of triple-shape memory to be incorporated into biomedical devices and strategies.

Printing Parameters of Fused Filament Fabrication Affect Key Properties of Four-Dimensional Printed Shape-Memory Polymers.

Extrusion-based (fused filament fabrication) three-dimensional (3D) printing of shape-memory polymers (SMPs) has the potential to rapidly produce highly customized smart-material parts. Yet, the effects of printing parameters on the shape-memory properties of printed SMPs remain poorly understood. To study the extent to which the 3D printing process affects the shape-memory properties of a printed SMP part, here temperature, extrusion rate multiplier, and fiber orientation were systematically varied, and their effect on shape-memory fixing and recovery ratios was evaluated. Fiber orientation, as determined by print path relative to the direction(s) of loading during shape-memory programming, was found to significantly impact the fixing ratio and the recovery ratio. Temperature and multiplier had little effect on either fixing ratio or recovery ratio. To facilitate the use of printed SMP parts in biomedical applications, a cell viability assay was performed on 3D-printed samples prepared using varied temperature and multiplier. Reduction in multiplier was found to increase cell viability. The results indicate that fiber orientation can critically impact the shape-memory functionality of 3D-printed SMP parts, and that multiplier can affect cytocompatibility of those parts. Thus, researchers and manufacturers employing SMPs in 3D-printed parts and devices could achieve improved part functionality if print paths are designed to align fiber direction with the axis(es) in which strain will be programmed and recovered and if the multiplier is optimized in biomedical applications in which a part will contact cells.

Surface Functionalization of 4D Printed Substrates Using Polymeric and Metallic Wrinkles.

Wrinkle topographies have been studied as simple, versatile, and in some cases biomimetic surface functionalization strategies. To fabricate surface wrinkles, one material phenomenon employed is the mechanical-instability-driven wrinkling of thin films, which occurs when a deforming substrate produces sufficient compressive strain to buckle a surface thin film. Although thin-film wrinkling has been studied on shape-changing functional materials, including shape-memory polymers (SMPs), work to date has been primarily limited to simple geometries, such as flat, uniaxially-contracting substrates. Thus, there is a need for a strategy that would allow deformation of complex substrates or 3D parts to generate wrinkles on surfaces throughout that complex substrate or part. Here, 4D printing of SMPs is combined with polymeric and metallic thin films to develop and study an approach for fiber-level topographic functionalization suitable for use in printing of arbitrarily complex shape-changing substrates or parts. The effect of nozzle temperature, substrate architecture, and film thickness on wrinkles has been characterized, as well as wrinkle topography on nuclear alignment using scanning electron microscopy, atomic force microscopy, and fluorescent imaging. As nozzle temperature increased, wrinkle wavelength increased while strain trapping and nuclear alignment decreased. Moreover, with increasing film thickness, the wavelength increased as well.

Cooperation between myofibril growth and costamere maturation in human cardiomyocytes.

Costameres, as striated muscle-specific cell adhesions, anchor both M-lines and Z-lines of the sarcomeres to the extracellular matrix. Previous studies have demonstrated that costameres intimately participate in the initial assembly of myofibrils. However, how costamere maturation cooperates with myofibril growth is still underexplored. In this work, we analyzed zyxin (costameres), α-actinin (Z-lines) and myomesin (M-lines) to track the behaviors of costameres and myofibrils within the cardiomyocytes derived from human induced pluripotent stem cells (hiPSC-CMs). We quantified the assembly and maturation of costameres associated with the process of myofibril growth within the hiPSC-CMs in a time-dependent manner. We found that asynchrony existed not only between the maturation of myofibrils and costameres, but also between the formation of Z-costameres and M-costameres that associated with different structural components of the sarcomeres. This study helps us gain more understanding of how costameres assemble and incorporate into the cardiomyocyte sarcomeres, which sheds a light on cardiomyocyte mechanobiology.

Cell-Responsive Shape Memory Polymers.

Recent decades have seen substantial interest in the development and application of biocompatible shape memory polymers (SMPs), a class of "smart materials" that can respond to external stimuli. Although many studies have used SMP platforms triggered by thermal or photothermal events to study cell mechanobiology, SMPs triggered by cell activity have not yet been demonstrated. In a previous work, we developed an SMP that can respond directly to enzymatic activity. Here, our goal was to build on that work by demonstrating enzymatic triggering of an SMP in response to the presence of enzyme-secreting human cells. To achieve this phenomenon, poly(ε-caprolactone) (PCL) and Pellethane were dual electrospun to form a fiber mat, where PCL acted as a shape-fixing component that is labile to lipase, an enzyme secreted by multiple cell types including HepG2 (human hepatic cancer) cells, and Pellethane acted as a shape memory component that is enzymatically stable. Cell-responsive shape memory performance and cytocompatibility were quantitatively and qualitatively analyzed by thermal analysis (thermal gravimetric analysis and differential scanning calorimetry), surface morphology analysis (scanning electron microscopy), and by incubation with HepG2 cells in the presence or absence of heparin (an anticoagulant drug present in the human liver that increases the secretion of hepatic lipase). The results characterize the shape-memory functionality of the material and demonstrate successful cell-responsive shape recovery with greater than 90% cell viability. Collectively, the results provide the first demonstration of a cytocompatible SMP responding to a trigger that is cellular in origin.

Femtosecond Laser Densification of Hydrogels to Generate Customized Volume Diffractive Gratings.

Inspired by nature's ability to shape soft biological materials to exhibit a range of optical functionalities, we report femtosecond (fs) laser-induced densification as a new method to generate volume or subsurface diffractive gratings within ordinary hydrogel materials. We characterize the processing range in terms of fs laser power, speed, and penetration depths for achieving densification within poly(ethylene glycol) diacrylate (PEGDA) hydrogel and characterize the associated change in local refractive index (RI). The RI change facilitates the fabrication of custom volume gratings (parallel line, grid, square, and ring gratings) within PEGDA. To demonstrate this method's broad applicability, fs laser densification was used to generate line gratings within the phenylboronic acid (PBA) hydrogel, which is known to be responsive to changes in pH. In the future, this technique can be used to convert ordinary hydrogels into multicomponent biophotonic systems.

Smart biomaterial platforms: Controlling and being controlled by cells.

Across diverse research and application areas, dynamic functionality-such as programmable changes in biochemical property, in mechanical property, or in microscopic or macroscopic architecture-is an increasingly common biomaterials design criterion, joining long-studied criteria such as cytocompatibility and biocompatibility, drug release kinetics, and controlled degradability or long-term stability in vivo. Despite tremendous effort, achieving dynamic functionality while simultaneously maintaining other desired design criteria remains a significant challenge. Reversible dynamic functionality, rather than one-time or one-way dynamic functionality, is of particular interest but has proven especially challenging. Such reversible functionality could enable studies that address the current gap between the dynamic nature of in vivo biological and biomechanical processes, such as cell traction, cell-extracellular matrix (ECM) interactions, and cell-mediated ECM remodeling, and the static nature of the substrates and ECM constructs used to study the processes. This review assesses dynamic materials that have traditionally been used to control cell activity and static biomaterial constructs, experimental and computational techniques, with features that may inform continued advances in reversible dynamic materials. Taken together, this review presents a perspective on combining the reversibility of smart materials and the in-depth dynamic cell behavior probed by static polymers to design smart bi-directional ECM platforms that can reversibly and repeatedly communicate with cells.

Profiling the responsiveness of focal adhesions of human cardiomyocytes to extracellular dynamic nano-topography.

Focal adhesion complexes function as the mediators of cell-extracellular matrix interactions to sense and transmit the extracellular signals. Previous studies have demonstrated that cardiomyocyte focal adhesions can be modulated by surface topographic features. However, the response of focal adhesions to dynamic surface topographic changes remains underexplored. To study this dynamic responsiveness of focal adhesions, we utilized a shape memory polymer-based substrate that can produce a flat-to-wrinkle surface transition triggered by an increase of temperature. Using this dynamic culture system, we analyzed three proteins (paxillin, vinculin and zyxin) from different layers of the focal adhesion complex in response to dynamic extracellular topographic change. Hence, we quantified the dynamic profile of cardiomyocyte focal adhesion in a time-dependent manner, which provides new understanding of dynamic cardiac mechanobiology.

Image-based cell subpopulation identification through automated cell tracking, principal component analysis, and partitioning around medoids clustering.

In vitro cell culture model systems often employ monocultures, despite the fact that cells generally exist in a diverse, heterogeneous microenvironment in vivo. In response, heterogeneous cultures are increasingly being used to study how cell phenotypes interact. However, the ability to accurately identify and characterize distinct phenotypic subpopulations within heterogeneous systems remains a major challenge. Here, we present the use of a computational, image analysis-based approach-comprising automated contour-based cell tracking for feature identification, principal component analysis for feature reduction, and partitioning around medoids for subpopulation characterization-to non-destructively and non-invasively identify functionally distinct cell phenotypic subpopulations from live-cell microscopy image data. Using a heterogeneous model system of endothelial and smooth muscle cells, we demonstrate that this approach can be applied to both mono and co-culture nuclear morphometric and motility data to discern cell phenotypic subpopulations. Morphometric clustering identified minimal difference in mono- versus co-culture, while motility clustering revealed that a portion of endothelial cells and smooth muscle cells adopt increased motility rates in co-culture that are not observed in monoculture. We anticipate that this approach using non-destructive and non-invasive imaging can be applied broadly to heterogeneous cell culture model systems to advance understanding of how heterogeneity alters cell phenotype. This work presents a computational, image-analysis-based approach-comprising automated contour-based cell tracking for feature identification, principle component analysis for feature reduction, and partitioning around medoids for subpopulation characterization-to non-destructively and non-invasively identify functionally distinct cell phenotypic subpopulations from live-cell microscopy image data.

Progressive Myofibril Reorganization of Human Cardiomyocytes on a Dynamic Nanotopographic Substrate.

Cardiomyocyte (CM) alignment with striated myofibril organization is developed during early cardiac organogenesis. Previous work has successfully achieved in vitro CM alignment using a variety of biomaterial scaffolds and substrates with static topographic features. However, the cellular processes that occur during the response of CMs to dynamic surface topographic changes, which may provide a model of in vivo developmental progress of CM alignment within embryonic myocardium, remains poorly understood. To gain insights into these cellular processes involved in the response of CMs to dynamic topographic changes, we developed a dynamic topographic substrate that employs a shape memory polymer coated with polyelectrolyte multilayers to produce a flat-to-wrinkle surface transition when triggered by a change in incubation temperature. Using this system, we investigated cellular morphological alignment and intracellular myofibril reorganization in response to the dynamic wrinkle formation. Hence, we identified the progressive cellular processes of human-induced pluripotent stem cell-CMs in a time-dependent manner, which could provide a foundation for a mechanistic model of cardiac myofibril reorganization in response to extracellular microenvironment changes.

High-Resolution 3D Printing of Stretchable Hydrogel Structures Using Optical Projection Lithography.

Double-network (DN) hydrogels, with their unique combination of mechanical strength and toughness, have emerged as promising materials for soft robotics and tissue engineering. In the past decade, significant effort has been devoted to synthesizing DN hydrogels with high stretchability and toughness; however, shaping the DN hydrogels into complex and often necessary user-defined two-dimensional (2D) and three-dimensional (3D) geometries remains a fabrication challenge. Here, we report a new fabrication method based on optical projection lithography to print DN hydrogels into customizable 2D and 3D structures within minutes. DN hydrogels were printed by first photo-crosslinking a single network structure via spatially modulated light patterns followed by immersing the printed structure in a calcium bath to induce ionic cross-linking. Results show that DN structures made by this method can stretch four times their original lengths. We show that strain and the elastic modulus of printed structures can be tuned based on the hydrogel composition, cross-linker and photoinitiator concentrations, and laser light intensity. To our knowledge, this is the first report demonstrating quick lithography and high-resolution printing of DN (covalent and ionic) hydrogels within minutes. The ability to shape tough and stretchable DN hydrogels in complex structures will be potentially useful in a broad range of applications.

Nuclear position relative to the Golgi body and nuclear orientation are differentially responsive indicators of cell polarized motility.

Cell motility is critical to biological processes from wound healing to cancer metastasis to embryonic development. The involvement of organelles in cell motility is well established, but the role of organelle positional reorganization in cell motility remains poorly understood. Here we present an automated image analysis technique for tracking the shape and motion of Golgi bodies and cell nuclei. We quantify the relationship between nuclear orientation and the orientation of the Golgi body relative to the nucleus before, during, and after exposure of mouse fibroblasts to a controlled change in cell substrate topography, from flat to wrinkles, designed to trigger polarized motility. We find that the cells alter their mean nuclei orientation, in terms of the nuclear major axis, to increasingly align with the wrinkle direction once the wrinkles form on the substrate surface. This change in alignment occurs within 8 hours of completion of the topographical transition. In contrast, the position of the Golgi body relative to the nucleus remains aligned with the pre-programmed wrinkle direction, regardless of whether it has been fully established. These findings indicate that intracellular positioning of the Golgi body precedes nuclear reorientation during mouse fibroblast directed migration on patterned substrates. We further show that both processes are Rho-associated kinase (ROCK) mediated as they are abolished by pharmacologic ROCK inhibition whereas mouse fibroblast motility is unaffected. The automated image analysis technique introduced could be broadly employed in the study of polarization and other cellular processes in diverse cell types and micro-environments. In addition, having found that the nuclei Golgi vector may be a more sensitive indicator of substrate features than the nuclei orientation, we anticipate the nuclei Golgi vector to be a useful metric for researchers studying the dynamics of cell polarity in response to different micro-environments.

Identifying the mechanism for superdiffusivity in mouse fibroblast motility.

We seek to characterize the motility of mouse fibroblasts on 2D substrates. Utilizing automated tracking techniques, we find that cell trajectories are super-diffusive, where displacements scale faster than t1/2 in all directions. Two mechanisms have been proposed to explain such statistics in other cell types: run and tumble behavior with Lévy-distributed run times, and ensembles of cells with heterogeneous speed and rotational noise. We develop an automated toolkit that directly compares cell trajectories to the predictions of each model and demonstrate that ensemble-averaged quantities such as the mean-squared displacements and velocity autocorrelation functions are equally well-fit by either model. However, neither model correctly captures the short-timescale behavior quantified by the displacement probability distribution or the turning angle distribution. We develop a hybrid model that includes both run and tumble behavior and heterogeneous noise during the runs, which correctly matches the short-timescale behaviors and indicates that the run times are not Lévy distributed. The analysis tools developed here should be broadly useful for distinguishing between mechanisms for superdiffusivity in other cells types and environments.

Enzymatically triggered shape memory polymers.

Cytocompatible shape memory polymers activated by thermal or photothermal triggers have been developed and established as powerful "smart material" platforms for both basic and translational research. Shape memory polymers (SMPs) that could be triggered directly by biological activity have not, in contrast, been reported. The goal of this study was to develop an SMP that responds directly to enzymatic activity and can do so under isothermal cell culture conditions. To achieve this goal, we designed an SMP with a shape fixing component, poly(ε-caprolactone) (PCL), that is vulnerable to enzymatic degradation and a shape memory component, Pellethane, that is enzymatically stable - as the shape fixing component undergoes enzymatically-catalyzed degradation, the SMP returns to its original, programmed shape. We quantitatively and qualitatively analyzed material properties, shape memory performance, and cytocompatibility of the enzymatically-catalyzed shape memory response. The results demonstrate enzymatic recovery, as contraction of tensile specimens, using bulk enzymatic degradation experiments and show that shape recovery is achieved by degradation of the PCL shape-fixing phase. The results further showed that both the materials and the process of enzymatic shape recovery are cytocompatible. Thus, the SMP design reported here represents both an enzyme responsive material capable of applying a programmed shape change or direct mechanical force and an SMP that could respond directly to biological activity. STATEMENT OF SIGNIFICANCE: Cytocompatible shape memory polymers activated by thermal or photothermal triggers have become powerful "smart material" platforms for basic and translational research. Shape memory polymers that could be triggered directly by biological activity have not, in contrast, been reported. Here we report an enzymatically triggered shape memory polymer that changes its shape isothermally in response to enzymatic activity. We successfully demonstrate enzymatic recovery using bulk enzymatic degradation experiments and show that shape recovery is achieved by degradation of the shape-fixing phase. We further show that both the materials and the process of enzymatic shape recovery are cytocompatible. This new shape memory polymer design can be anticipated to enable new applications in basic and applied materials science as a stimulus responsive material.

Shape memory activation can affect cell seeding of shape memory polymer scaffolds designed for tissue engineering and regenerative medicine.

The ability of a three-dimensional scaffold to support cell seeding prior to implantation is a critical criterion for many scaffold-based tissue engineering and regenerative medicine strategies. Shape memory polymer functionality may present important new opportunities and challenges in cell seeding, but the extent to which shape memory activation can positively or negatively affect cell seeding has yet to be reported. The goal of this study was to determine whether shape memory activation can affect cell seeding. The hypothesis was that shape memory activation of porous scaffolds during cell seeding can affect both the number of cells seeded in a scaffold and the distribution (in terms of average infiltration distance) of cells following seeding. Here, we used a porous shape memory foam scaffold programmed to expand when triggered to study cell number and average cell infiltration distance following shape memory activation. We found that shape memory activation can affect both the number of cells and the average cell infiltration distance. The effect was found to be a function of rate of shape change and scaffold pore interconnectivity. Magnitude of shape change had no effect. Only reductions in cell number and infiltration distance (relative to control and benchmark) were observed. The findings suggest that strategies for tissue engineering and regenerative medicine that involve shape memory activation in the presence of a cell-containing medium in vitro or in vivo should consider how recovery rate and scaffold pore interconnectivity may ultimately impact cell seeding.

How Bacteria Respond to Material Stiffness during Attachment: A Role of Escherichia coli Flagellar Motility.

Material stiffness has been shown to have potent effects on bacterial attachment and biofilm formation, but the mechanism is still unknown. In this study, response to material stiffness by Escherichia coli during attachment was investigated with biofilm assays and cell tracking using the Automated Contour-base Tracking for in Vitro Environments (ACTIVE) computational algorithm. By comparing the movement of E. coli cells attached on poly(dimethylsiloxane) (PDMS) surfaces of different Young's moduli (0.1 and 2.6 MPa, prepared by controlling the degree of cross-linking) using ACTIVE, attached cells on stiff surfaces were found more motile during early stage biofilm formation than those on soft surfaces. To investigate if motility is important to bacterial response to material stiffness, we compared E. coli RP437 and its isogenic mutants of flagellar motor (motB) and synthesis of flagella (fliC) and type I fimbriae (fimA) for attachment on 0.1 and 2.6 MPa PDMS surfaces. The motB mutant exhibited defects in response to PDMS stiffness (based on cell counting and tracking with ACTIVE), which was recovered by complementing the motB gene. Unlike motB results, mutants of fliC and fimA did not show significant defects on both face-up and face-down surfaces. Collectively, these findings suggest that E. coli cells can actively respond to material stiffness during biofilm formation, and motB is involved in this response.

On-command on/off switching of progenitor cell and cancer cell polarized motility and aligned morphology via a cytocompatible shape memory polymer scaffold.

In vitro biomaterial models have enabled advances in understanding the role of extracellular matrix (ECM) architecture in the control of cell motility and polarity. Most models are, however, static and cannot mimic dynamic aspects of in vivo ECM remodeling and function. To address this limitation, we present an electrospun shape memory polymer scaffold that can change fiber alignment on command under cytocompatible conditions. Cellular response was studied using the human fibrosarcoma cell line HT-1080 and the murine mesenchymal stem cell line C3H/10T1/2. The results demonstrate successful on-command on/off switching of cell polarized motility and alignment. Decrease in fiber alignment causes a change from polarized motility along the direction of fiber alignment to non-polarized motility and from aligned to unaligned morphology, while increase in fiber alignment causes a change from non-polarized to polarized motility along the direction of fiber alignment and from unaligned to aligned morphology. In addition, the findings are consistent with the hypothesis that increased fiber alignment causes increased cell velocity, while decreased fiber alignment causes decreased cell velocity. On-command on/off switching of cell polarized motility and alignment is anticipated to enable new study of directed cell motility in tumor metastasis, in cell homing, and in tissue engineering.

On-Demand Removal of Bacterial Biofilms via Shape Memory Activation.

Bacterial biofilms are a major cause of chronic infections and biofouling; however, effective removal of established biofilms remains challenging. Here we report a new strategy for biofilm control using biocompatible shape memory polymers with defined surface topography. These surfaces can both prevent bacterial adhesion and remove established biofilms upon rapid shape change with moderate increase of temperature, thereby offering more prolonged antifouling properties. We demonstrate that this strategy can achieve a total reduction of Pseudomonas aeruginosa biofilms by 99.9% compared to the static flat control. It was also found effective against biofilms of Staphylococcus aureus and an uropathogenic strain of Escherichia coli.