Stimuli-responsive Systems Research Articles

Multicompartment colloid systems with lipid and polymer membranes for biomedical applications.

Multicompartment structures have the potential for biomedical applications because they can act as multifunctional systems and provide simultaneous delivery of drugs and diagnostics agents of different types. Moreover, some of them mimic biological cells to some extent with organelles as separate sub-compartments. This article analyses multicompartment colloidal structures with smaller sub-units covered with lipid or polymer membranes that provide additional protection for the encapsulated substances. Vesosomes with small vesicles encapsulated in the inner pools of larger liposomes are the most studied systems to date. Dendrimer molecules are enclosed by a lipid bilayer shell in dendrosomes. Capsosomes, polymersomes-in-polymer capsules, and cubosomes-in-polymer capsules are composed of sub-compartments encapsulated within closed multilayer polymer membranes. Janus or Cerberus emulsions contain droplets composed of two or three phases: immiscible oils in O/W emulsions and aqueous polymer or salt solutions that are separated into two or three phases and form connected droplets in W/O emulsions. In more cases, the external surface of engulfed droplets in Janus or Cerberus emulsions is covered with a lipid or polymer monolayer. eLiposomes with emulsion droplets encapsulated into a bilayer shell have been given little attention so far, but they have very great prospects. In addition to nanoemulsion droplets, solid lipid nanoparticles, nanostructured lipid carriers and inorganic nanoparticles can be loaded into eLiposomes. Molecular engineering of the external membrane allows the creation of ligand-targeted and stimuli-responsive multifunctional systems. As a result, the efficacy of drug delivery can be significantly enhanced.

Research progress of stimuli-responsive ZnO-based nanomaterials in biomedical applications.

Zinc oxide nanoparticles (ZnO NPs), an attractive oxide semiconductor material, are widely used in the biomedical field due to their good biosafety and economy. The proposal of stimuli-responsive materials provides a new way for the further application of single ZnO-based nanomaterials that cannot meet the ever-changing requirements. In this review, the emerging advances in exogenous stimuli (light, ultrasound, mechanical force, etc.) and endogenous stimuli (pH, enzymes, etc.) responsive systems of ZnO-based nanomaterials in biomedical applications are highlighted. First, the basic characteristics, response mechanisms and construction principles of single-stimulus-responsive ZnO-based nanomaterials, as well as their recent advances in tissue repair, medical devices and theranostics are summarized. Subsequently, the design method of multi-stimuli-responsive ZnO-based biomaterials is discussed, and the application advantages of multi-functional responsive systems are explained by analyzing typical cases of biomedical applications of multi-responsive strategies. Finally, we discuss the prospects for the design and development of stimuli-responsive ZnO-based biomaterials for biomedical applications and point out their advantages as well as the places that need to be further improved. The current review may provide a useful reference for researchers interested in constructing such abundant, inexpensive and widely applicable multi-stimuli-responsive materials.

Multifunctional Oxidized Succinoglycan/Poly(N-isopropylacrylamide-co-acrylamide) Hydrogels for Drug Delivery

We prepared the self-healing and temperature/pH-responsive hydrogels using oxidized succinoglycan (OSG) and a poly (N-isopropyl acrylamide-co-acrylamide) [P(NIPAM-AM)] copolymer. OSG was synthesized by periodate oxidation of succinoglycan (SG) isolated directly from soil microorganisms, Sinorhizobium meliloti Rm1021. The OSG/P(NIPAM-AM) hydrogels were obtained by introducing OSG into P(NIPAM-AM) networks. The chemical structure and physical properties of these hydrogels were characterized by ATR-FTIR, XRD, TGA, and FE-SEM. The OSG/P(NIPAM-AM) hydrogels showed improved elasticity, increased thermal stability, new self-healing ability, and 4-fold enhanced tensile strength compared with the P(NIPAM-AM) hydrogels. Furthermore, the 5-FU-loaded OSG/P(NIPAM-AM) hydrogels exhibited effective temperature/pH-responsive drug release. Cytotoxicity experiments showed that the OSG/P(NIPAM-AM) hydrogels were non-toxic, suggesting that OSG/P(NIPAM-AM) hydrogels could have the potential for biomedical applications, such as stimuli-responsive drug delivery systems, wound healing, smart scaffolds, and tissue engineering.

A Triazolium-Anchored Self-Immolative Linker Enables Self-Assembly-Driven siRNA Binding and Esterase-Induced Release.

The increased importance of RNA-based therapeutics comes with a need to develop next-generation stimuli-responsive systems capable of binding, transporting and releasing RNA oligomers. In this work, we describe triazolium-based amphiphiles capable of siRNA binding and enzyme-responsive release of the nucleic acid payload. In aqueous medium, the amphiphile self-assembles into nanocarriers that can disintegrate upon the addition of esterase. Key to the molecular design is a self-immolative linker that is anchored to the triazolium moiety and acts as a positively-charged polar head group. We demonstrate that addition of esterase leads to a degradation cascade of the linker, leaving the neutral triazole compound unable to form complexes and therefore releasing the negatively-charged siRNA. The reported molecular design and overall approach may have broad utility beyond this proof-of-principle study, because the underlying CuAAC "click" chemistry allows bringing together three groups very efficiently as well as cleaving off one of the three groups under the mild action of an esterase enzyme.

Historical Perspectives and Recent Research on DNA Hydrogel-Based Stimuli-Responsive Systems and Bioengineering Applications

Soft hydrogel materials have attracted increasing attention from scientists due to the programmability of nucleic acids. DNA hydrogels are increasingly used in biomedicine due to their natural biocompatibility and degradation properties. Moreover, the addition of various molecules to these hydrogels can enhance the superiority and utility of DNA hydrogels. Therefore, the present study aimed to provide a timely overview of historical perspectives and recent research advances in DNA hydrogels and their applications in bioengineering and stimulus-responsive systems. The state-of-the-art problems and future prospects of DNA hydrogels were also discussed.

Metal-Photoswitch Friendship: From Photochromic Complexes to Functional Materials.

Cooperative metal-photoswitch interfaces comprise an application-driven field which is based on strategic coupling of metal cations and organic photochromic molecules to advance the behavior of both components, resulting in dynamic molecular and material properties controlled through external stimuli. In this Perspective, we highlight the ways in which metal-photoswitch interplay can be utilized as a tool to modulate a system's physicochemical properties and performance in a variety of structural motifs, including discrete molecular complexes or cages, as well as periodic structures such as metal-organic frameworks. This Perspective starts with photochromic molecular complexes as the smallest subunit in which metal-photoswitch interactions can occur, and progresses toward functional materials. In particular, we explore the role of the metal-photoswitch relationship for gaining fundamental knowledge of switchable electronic and magnetic properties, as well as in the design of stimuli-responsive sensors, optically gated memory devices, catalysts, and photodynamic therapeutic agents. The abundance of stimuli-responsive systems in the natural world only foreshadows the creative directions that will uncover the full potential of metal-photoswitch interactions in the coming years.

PH-Responsive, Thermo-Resistant Poly(Acrylic Acid)-g-Poly(boc-L-Lysine) Hydrogel with Shear-Induced Injectability.

In this study we report the rheological behavior of aqueous solutions of an amphiphilic graft copolymer constituting a polyacrylic acid (PAA) grafted by poly(boc-L-lysine), P(b-LL). Due to the highly hydrophobic nature of the grafted chains, the copolymer self-assembles spontaneously in aqueous media forming three-dimensional (3D) finite size networks (microgels). The rheological analysis demonstrated that the copolymer behaves as a strong elastic hydrogel, showing characteristics of a "frozen" network. Moreover, it is noteworthy that the formulation shows the above-described characteristics in very small concentrations (0.25-1.20 wt%) compared to other naturally cross-linked hydrogels that have been studied so far. Concentration significantly affects the rheological properties of the hydrogel, showing considerable increase in elastic modulus, following the scaling law G'~C1.93. At the same time, the hydrogels can be described as intelligent stimuli-responsive systems, showing pH and shear responsiveness as well as stability with temperature changes. Thanks to the pH dependance of the degree of ionization of the weak polyelectrolyte PAA backbone, stiffness and swelling of the hydrogels can be tuned effectively by adjusting the pH conditions. Simulating conditions such as those of injection through a 28-gauge syringe needle, the gel demonstrates excellent response to shear, due to its remarkable shear thinning behavior. The combination of pH-sensitivity and shear responsiveness leads to excellent injectability and self-healing properties, given that it flows easily upon applying a low stress and recovers instantly in the site of injection. Therefore, the physically cross-linked PAA-g-P(b-LL) hydrogel exhibits remarkable features, namely biocompatibility, biodegradability of cross-links, pH responsiveness, shear-induced injectability and instantaneous self-healing, making it a potential candidate for various biomedical applications.

Thermoresponsive reversible host-guest supramolecular nanotubular self-assembly of octyl-2-acetoxybenzoate@β-CD

The present work deals with supramolecular host–guest complexation of octyl-2-acetoxybenzoate (OCASP) into β-cyclodextrin (β-CD) which spontaneously self-assembled into a thermoresponsive nanotubular architecture at a molar ratio of 1:1. OCASP was synthesized as a prodrug of aspirin (ASP) in an aim to reduce its inherent toxicity. The OCASP@β-CD inclusion complex (IC) was characterized by UV–Vis, FT-IR, WAXRD, 13C CP/MAS NMR spectroscopy and SEM. TEM and AFM revealed the formation of nanotube with a diameter of ∼50 nm. Reversible switching of assembly and disassembly is triggered by decreasing and increasing of temperature, as is evidenced by the turbidity measurement of a 5% solution of OCASP@β-CD system. Hydrophobic interactions among the successive OCASP@β-CDs are the chief driving force behind the formation of hierarchy as is evidenced by the control experiment with urea during its preparation. The stepwise formation of such a hierarchy was further characterised by molecular dynamics (MD) studies in 15 ns time scale using 2 fs time step. The developed stimuli responsive system would permit tailoring of its physical properties and it is anticipated that it will bring light on the fabrication of novel smart materials.

Synthesis of Thermoresponsive, Catechol-Rich Poly(ethylene glycol) Brush Polymers for Attenuating Cellular Oxidative Stress.

Herein, we report a platform to integrate customizable quantities of catechol units into polymers by reacting caffeic acid carbonic anhydride with polymers having pendant amine groups. Brush poly(ethylene glycol)-caffeamide (PEG-CAF) copolymers based on oligo(ethylene glycol)methyl ether methacrylate (OEGMA500) were obtained with a catechol content of approximately 30, 40, and 50 mol % (vs OEGMA content). Owing to the hydrophobicity of the introduced CAF groups, the catechol copolymers exhibited cloud points in the range of 23-46 °C and were used to fabricate thermoresponsive FeIII metal-phenolic network capsules. Polymers with the highest CAF content (50 mol %) proved most effective for attenuating reactive oxygen species levels in vitro, in co-cultured fibroblasts, and breast cancer cells, even in the presence of an exogenous oxidant source. The reported approach to synthesize customizable catechol materials could be generalized to other amine-functional polymers, with potential biomedical applications such as adhesives or stimuli-responsive drug delivery systems.

Stimuli-responsive and biomimetic delivery systems for sepsis and related complications.

Sepsis, a consequence of an imbalanced immune response to infection, is currently one of the leading causes of death globally. Despite advances in the discoveries of potential targets and nanotechnology, sepsis still lacks effective drug delivery systems for optimal treatment. Stimuli-responsive and biomimetic nano delivery systems, specifically, are emerging as advanced bio-inspired nanocarriers for enhancing the treatment of sepsis. Herein, we present a critical review of different stimuli-responsive systems, including pH-; enzyme-; ROS- and toxin-responsive nanocarriers, reported in the delivery of therapeutics for sepsis. Biomimetic nanocarriers, utilizing natural pathways in the inflammatory cascade to optimize sepsis therapy, are also reviewed, in addition to smart, multifunctional vehicles. The review highlights the nanomaterials designed for constructing these systems; their physicochemical properties; the mechanisms of drug release; and their potential for enhancing the therapeutic efficacy of their cargo. Current challenges are identified and future avenues for research into the optimization of bio-inspired nano delivery systems for sepsis are also proposed. This review confirms the potential of stimuli-responsive and biomimetic nanocarriers for enhanced therapy against sepsis and related complications.

Recent Advances in Stimuli-Responsive Doxorubicin Delivery Systems for Liver Cancer Therapy.

Doxorubicin (DOX) is one of the most commonly used drugs in liver cancer. Unfortunately, the traditional chemotherapy with DOX presents many limitations, such as a systematic release of DOX, affecting both tumor tissue and healthy tissue, leading to the apparition of many side effects, multidrug resistance (MDR), and poor water solubility. Furthermore, drug delivery systems' responsiveness has been intensively studied according to the influence of different internal and external stimuli on the efficiency of therapeutic drugs. In this review, we discuss both internal stimuli-responsive drug-delivery systems, such as redox, pH and temperature variation, and external stimuli-responsive drug-delivery systems, such as the application of magnetic, photo-thermal, and electrical stimuli, for the controlled release of Doxorubicin in liver cancer therapy, along with the future perspectives of these smart delivery systems in liver cancer therapy.

Advances in stimuli-responsive systems for pesticides delivery: Recent efforts and future outlook.

Effective pest management for enhanced crop output is one of the primary goals of establishing sustainable agricultural practices in the world. Pesticides are critical in preventing biological disasters, ensuring crop productivity, and fostering sustainable agricultural production growth. Studies showed that crops are unable to properly utilize pesticides because of several limiting factors, such as leaching and bioconversion, thereby damaging ecosystems and human health. In recent years, stimuli-responsive systems for pesticides delivery (SRSP) by nanotechnology demonstrated excellent promise in enhancing the effectiveness and safety of pesticides. SRSP are being developed with the goal of delivering precise amounts of active substances in response to biological needs and environmental factors. An in-depth analysis of carrier materials, design fundamentals, and classification of SRSP were provided. The adhesion of SRSP to crop tissue, absorption, translocation in and within plants, mobility in the soil, and toxicity were also discussed. The problems and shortcomings that need be resolved to accelerate the actual deployment of SRSP were highlighted in this review.

Mesoporous silica gated mixed micelle for the targeted co-delivery of doxorubicin and paclitaxel

Breast cancer is the second most common cancer in women worldwide. A nano-drug delivery system (DDS) was fabricated by cooperating with two drug carriers (mesoporous silica nanoparticles and mixed micelles), providing a suitable method for designing stimuli-responsive drug delivery systems. The system is developed using paclitaxel (PTX) loaded mixed micelle as gating agents and doxorubicin (DOX) loaded mesoporous silica nanoparticles via Schiff base. Because of the pH-sensitive Schiff base, the gating micelles can achieve drug release under the acidic condition at pH = 5.5. In the present DDS, the Arginine-glycine-aspartic acid (RGD) peptide was utilized to target the specific cancer cell. The DDS shows 81.0% PTX and 65.0% DOX release after 72 h. The DDS was characterized well by FT-IR, UV-VIS, FE-SEM, BET, 1H NMR, and DLS. The newly formulated DDS was also examined by apoptosis to assess its pharmaceutical field application. The study results suggested that developed DDS serves as a potential device for targeted delivery and controlled release of DOX & PTX for cancer treatment.

A Compendious Review on Biodegradable Polymeric Nanoparticles

Polymeric nanoparticles (NPs) are among the eminently designed organic nanomedicine. There is a lot of elation about polymeric NPs' potential to revolutionize modern medicine. Particle size, morphology, material selection, and processing methods are all being studied to synthesize the perfect nanosystem for effectual and precisely target bioactive. PNPs have the ability to significantly elevate the potency of therapeutic medication by allowing for targeted distribution to a specific location. Drug delivery techniques such as conjugation and trapping of medicines, prodrugs, stimuli-responsive systems, imaging modalities, and theranostics all use polymeric NPs. The review focuses on the array of existing approaches for the producing of polymeric nanoparticles. We want to draw attention to several natural and synthetic biodegradable polymers. Polymers' physiochemical properties can be tweaked to provide distribution through several biological barriers in order to reach distinct organs or cells. The use of biodegradable polymers as nanocarriers is particularly appealing since these materials can be tailored to degrade in physiological system. Additionally, in the next part, the characterization methods for this type of nanoparticles are discussed.

Folic acid-poly(N-isopropylacrylamide-maltodextrin) nanohydrogels as novel thermo-/pH-responsive polymer for resveratrol breast cancer targeted therapy

BackgroundThe long-term sequelae and serious side effects of conventional breast cancer chemotherapy due to ubiquitous biodistribution and systemic toxicity remain the main obstacle to success in clinic. Recent anticancer research rely on tailoring smart carriers to overcome these drawbacks. In this regard, numerous stimuli-responsive polymers have been assembled and successfully employed as smart carriers various chemotherpeutic agents due to their intrinsic tumor targeting properties. Among which, poly(N-isopropylacrylamide (PNIPAM) has gained increasing attention being amenable to various chemical modifications for tuning its intrinsic thermoresponsivity or endowing additional stimulus responsiveness. This work aims to develop PNIPAM-maltodextrin nanohydrogels (PNIPAM-MD NGs) decorated with folic acid (FA) as smart breast cancer-targeted stimuli-responsive delivery system to the natural polyphenol resveratrol (RSV) suffering from low bioavailaibity. ResultsPNIPAM-MD was synthesized by graft copolymerization, characterized and evaluated for its modulated stimuli-responsivity. The PNIPAM-based copolymer was coupled with FA, the breast cancer active targeting ligand. The FA-PNIPAM-MD NGs core was loaded RSV, then subjected to in vitro and in vivo evaluation. Results showed that the developed RSV-loaded FA-PNIPAM-MD (F3) NGs displayed dual thermo- and pH-responsivities, high drug-loading capacity (8.31 wt%,) and excellent physical and serum stability. The targeted formula F3 exhibited enhanced in vitro anti-breast cancer potency as evident by 7.4 folds reduction in the IC50 of free RSV and significant MCF-7 cellular uptake. In breast cancer-bearing mice, F3 suppressed the tumor growth, lowered VEGF-1 and Ki-67 expression levels, and induced apoptosis via upregulating caspase-3. ConclusionOverall, the PNIPAM-MD NGs as well as its FA-decorated breast cancer-targted NGs could serve as promising smart nanocarrier for efficient RSV brest cancer delivery. It could be safely deduced that the assembled FA-PNIPAM-MD F3 NGs enabled sequestering the therapeutic cargo (RSV) in normal tissue and released it in tumor site, thus guarding against its rapid metabolism and maximizing its accumulation in the cancer tissue as evidenced by the remarkable tumor growth suppression noticed in the targeted RSV/FA-PNIPAM-MD F3 NGs-treated mice compared to that in the free RSV-treated group. Hence, The fabricated nanohydrogels may be further employed for smart delivery of various anti-breast cancer agents.

PH and NIR responsive polydopamine-doped dendritic silica carriers for pesticide delivery

The stimuli-responsive pesticide delivery system provides a powerful strategy for enhancing the effective utilization of pesticides and reducing environmental pollution. Here, we prepared a new polydopamine doped dendritic silica (SiO2/PDA) nanocarriers for pesticide delivery. The SiO2/PDA nanocarriers present uniform spheres with an average diameter of 250 nm and carry center-radial inner pores. After loading dinotefuran (DNF) insecticide, polyethyleneimine (PEI) was used to cap the loaded-pesticide pores. The resulting SiO2/PDA@PEI displays high photothermal conversion effect (η = 35.1 %) and pH and near infrared (NIR) light-responsive release behavior. Meanwhile, the SiO2/PDA and SiO2/PDA@PEI carriers displayed high adhesion and wettability to leaves, and the photostability of DNF encapsulated in SiO2/PDA@PEI was improved by nearly 10 times greater than for free DNF. Importantly, the SiO2/PDA carriers possessed a benign biocompatibility on Escherichia coli (E. coli), seed and cells. Therefore, this work provides a promising approach to improve the utilization of pesticide.

Controlled release fertilizer with temperature-responsive behavior coated using polyether polyol (PPG) / polycaprolactone (PCL) blend-based polyurethane performs smart nutrient release

The development of the temperature-responsive controlled release fertilizers (CRFs) can tune the nutrient release matching plant demands even when temperature fluctuates. Herein, polycaprolactone (PCL) with different molecular weights (PCL500, PCL1000, PCL2000 and PCL3000) were used as raw materials and six types of PU films as coating materials for CRFs were synthesized by reacting the polyether polyol (PPG)/PCL blends and methylene diphenyl diisocyanate (MDI). Furthermore, the CRFs coated using PU films (PUCFs) were prepared in a fluidized bed device by in-situ reaction method, and the nitrogen (N) release rate of PUCFs was measured by water immersion experiment. The temperature sensitivity and compositions of PU films were evaluated with differential scanning calorimetry (DSC), Fourier transform infrared (FTIR) spectroscopy and X-ray diffraction (XRD). Results showed that PUCFs based on PCL500 satisfied the CRF ISO standard, but the corresponding PU film had no temperature-responsive property. However, PUCFs based on PCL2000 and the corresponding PU film showed the opposite results. FTIR and XRD results showed that the PPG/PCL2000 blends could copolymerize with MDI to format the block copolymer with the two-phase structure of crystalline phase/amorphous phase. The block copolymer comprising of PPG and PCL2000 at a molar ratio of 8 to 2 was indicated to have shape memory characteristics and the CRFs coated by this copolymer had excellent N release characteristics with a controlled release period of more than 30 days. Moreover, these CRFs showed significant temperature-switch at 33 °C. In conclusion, the production of temperature-responsive PUCF which is suitable for the application into agriculture will improve nutrient availability, indicating that the stimuli-responsive system has potential application in sustainable and green development of agriculture.

Unperceivable motion mimicking hygroscopic geometric reshaping of pine cones.

The hygroscopic deformation of pine cones, featured by opening and closing their scales depending on the environmental humidity, is a well-known stimuli-responsive model system for artificial actuators. However, it has not been noted that the deformation of pine cones is an ultra-slow process. Here, we reveal that vascular bundles with unique parallelly arranged spring/square microtubular heterostructures dominate the hygroscopic movement, characterized as ultra-slow motion with the outer sclereids. The spring microtubes give a much larger hygroscopic deformation than that of the square microtubes along the longitudinal axis direction, which bends the vascular bundles and consequently drives the scales to move. The outer sclereids with good water retention enable the vascular-bundle-triggered deformation to proceed ultra-slowly. Drawing inspiration, we developed soft actuators enabling controllable yet unperceivable motion. The motion velocity is almost two orders of magnitude lower than that of the same-class actuators reported, which made the as-developed soft actuators applicable in camouflage and reconnaissance.

Thermosensitive In Situ Gels for Joint Disorders: Pharmaceutical Considerations in Intra-Articular Delivery.

The intra-articular administration of conventional drug solutions or dispersions in joint diseases such as osteoarthritis has a relatively short retention time and, therefore, limited therapeutic effect. Thermosensitive polymer solutions that exhibit a sol-gel phase transition near body temperature after injection can prolong drug retention by providing a depot from which the drug release is sustained while relieving inflammation and preventing degradation of the joint complex. Thermosensitive hydrogels have in recent times garnered considerable attention in the intra-articular therapeutics of joint diseases such as osteoarthritis. Among the stimuli-responsive gelling systems, most research has focused on thermosensitive hydrogels. These gels are preferred over other stimuli-sensitive hydrogels since they have well-controlled in situ gelling properties and are also easier to load with drugs. Temperature-sensitive polymers, such as block copolymers or poloxamers, are frequently used to modify their gelation properties, usually in combination with other polymers. They are compatible with most drugs but may pose formulation challenges in terms of their low-response time, highly fragile nature, and low biocompatibility. The stability and biodegradability of implant hydrogels can control the drug release rate and treatment efficacy. This review stresses the application of thermosensitive gels in joint disorders and summarizes recent developments for intra-articular application, including the incorporation of nanoparticles. The hydrogel composition, drug release mechanisms, and the challenges involved in their formulation and storage are also discussed.

Bioderived materials for stimuli-responsive, adaptive, and neuromorphic systems: A perspective

In this concept article, we review recent works on the use of biologically-derived materials, including biomolecules, hybrid biomolecular composites, and natural tissues for achieving stimuli-responsiveness, adaptability, and memory storage for potential neuromorphic computing applications. Unlike solid-state materials, bioderived platforms are often intrinsically modular, including possessing the ability to leverage the diversity of naturally multifunctional biomolecules, cornerstones in biological transduction, signaling, and learning. The primary neuromorphic functionality of bioderived systems considered here is memory resistance, as obtained through combinations of resistive switching, activity-dependent plasticity, and memory storage. In some cases, these capabilities are achieved in bio-derived systems by closely emulating the structure, function, or signaling mechanisms found in living neurons. Our review considers bioderived systems that span multiple length scales and levels of hierarchical complexity: from single-molecule enabled devices to intact tissues, interrogated either in vitro or in vivo on living organisms. Through this exercise, we offer our perspective on research opportunities in the development and use of synapse- and neuron-inspired bioderived systems, including the prospect of biocompatible, and even tissue-like, neuromorphic materials to smartly monitor and treat injury and disease, deliver therapeutics, and interpret neural activity. These capabilities could unlock a new generation of smart, adaptable bioderived composites that autonomously report, learn (i.e., classify, forecast), compute, and actuate in the direct vicinity of living cells and tissues, i.e. at the edge of biology.