Platform For Biomedical Applications Research Articles

(Invited) Derivatizing Fullerenes and Metallofullerenes for Biomedicine

Fullerenes and metallofullerenes are excellent building blocks for biomedicines due to their carbon-based structures that allows for biocompatible materials being built with robust C-C covalent bonds. The hexakis-Bingel reaction can introduce up to 12 functional groups onto one C60 core and provide a versatile platform for molecularly precise, “nanoparticle-like” functional materials. In this presentation we hope to report our recent utilization of the hexakisadduct platform in biomedical applications. In the first study we investigated the anti-oxidative behavior of a series of C60 derivatives, where the hexakisadduct turned out to be an excellent reactive oxygen species scavenger. Then we exemplify the ligand introduction to the hexakisadduct core with Gd metallofullerens, which leads to a series of structurally defined, efficient and safe MRI contrast agents.

Exploring Supramolecular Interactions between the Extracellular-Matrix-Derived Minimalist Bioactive Peptide and Nanofibrillar Cellulose for the Development of an Advanced Biomolecular Scaffold.

It has been increasingly evident over the last few years that bioactive peptide hydrogels in conjugation with polymer hydrogels are emerging as a new class of supramolecular materials suitable for various biomedical applications owing to their specificity, tunability, and nontoxicity toward the biological system. Despite their unique biocompatible features, both polymer- and peptide-based scaffolds suffer from certain limitations, which restrict their use toward developing efficient matrices for controlling cellular behavior. The peptide hydrogels usually form soft matrices with low mechanical strength, whereas most of the polymer hydrogels lack biofunctionality. In this direction, combining polymers with peptides to develop a conjugate hydrogel can be explored as an emergent approach to overcome the limitations of the individual components. The polymer will provide high mechanical strength, whereas the biofunctionality of the material can be induced by the bioactive peptide sequence. In this study, we utilized TEMPO-oxidized nanofibrillar cellulose as the polymer counterpart, which was co-assembled with a short N-cadherin mimetic bioactive peptide sequence, Nap-HAVDI, to fabricate an NFC-peptide conjugate hydrogel. Interestingly, the mechanical strength of the peptide hydrogel was found to be significantly improved by combining the peptide with the NFC in the conjugate hydrogel. The addition of the peptide into the NFC also reduced the pore size within NFC matrices, which further helped in improving cellular adhesion, survival, and proliferation. Furthermore, the cells grown on the NFC and NFC-peptide hybrid hydrogel demonstrated normal expression of cytoskeleton proteins, i.e., β-tubulin in C6 cells and actin in L929 cells, respectively. The selective response of neuronal cells toward the specific bioactive peptide was further observed through a protein expression study. Thus, our study demonstrated the collective role of the cellulose-peptide composite material that revealed superior physical properties and biological response of this composite scaffold, which may open up a new platform for biomedical applications.

Construction and Functionalization of a Clathrin Assembly for a Targeted Protein Delivery.

Protein assemblies have drawn much attention as platforms for biomedical applications, including gene/drug delivery and vaccine, due to biocompatibility and functional diversity. Here, the construction and functionalization of a protein assembly composed of human clathrin heavy chain and light chain for a targeted protein delivery, is presented. The clathrin heavy and light chains are redesigned and associated with each other, and the resulting triskelion unit further self-assembled into a clathrin assembly with the size of about 28nm in diameter. The clathrin assembly is dual-functionalized with a protein cargo and a targeting moiety using two different orthogonal protein-ligand pairs through one-pot reaction. The functionalized clathrin assembly exhibits about a 900-fold decreased KD value for a cell-surface target due to avidity compared to a native targeting moiety. The utility of the clathrin assembly is demonstrated by an efficient delivery of a protein cargo into tumor cells in a target-specific manner, resulting in a strong cytotoxic effect. The present approach can be used in the creation of protein assemblies with multimodality.

MoSBOTs: Magnetically Driven Biotemplated MoS2 -Based Microrobots for Biomedical Applications.

2D layered molybdenum disulfide (MoS2 ) nanomaterials are a promising platformfor biomedical applications, particularly due to its high biocompatibility characteristics, mechanical and electrical properties, and flexible functionalization. Additionally, the bandgap of MoS2 can be engineered to absorb light over a wide range of wavelengths, which can then be transformed into local heat for applications in photothermal tissue ablation and regeneration. However, limitations such as poor stability of aqueous dispersions and low accumulation in affected tissues impair the full realization of MoS2 for biomedical applications. To overcome such challenges, herein, multifunctional MoS2 -based magnetic helical microrobots (MoSBOTs) using cyanobacterium Spirulina platensis are proposed as biotemplate for therapeutic and biorecognition applications. The cytocompatible microrobots combine remote magnetic navigation with MoS2 photothermal activity under near-infrared irradiation. The resulting photoabsorbent features of the MoSBOTs are exploited for targeted photothermal ablation of cancer cells and on-the-fly biorecognition in minimally invasive oncotherapy applications. The proposed multi-therapeutic MoSBOTs hold considerable potential for a myriad of cancer treatment and diagnostic-related applications, circumventing current challenges of ablative procedures.

Bacteriophage‐built gels as platforms for biomedical applications

AbstractBacteriophages, or phages (bacterial viruses), have seen a resurgence in their applications following the emergence of antimicrobial‐resistant superbugs that pose enormous risks to human health and food supplies. Phages present numerous advantages over conventional small‐molecule antibiotics, including that they are highly selective bacteria‐killers and demonstrate low inherent cytotoxicity to human health. Notwithstanding the direct therapeutic applications of these innate bacteria‐killing viruses, they have also garnered attention as biological nanoparticles. Due to the diversity in sizes and shapes of phages, self‐replicating capacity, geometrical batch‐to‐batch consistency, and ease of synthetic modifications, phages are excellent building blocks for creating bioactive biomaterial platforms. In this review, we provide a brief history of the development of phage‐based materials and identify key stakeholders who are driving innovation in this space. In addition, we explore various phage‐based gel structures and provide a critical analysis of how their structures produce distinct advantageous properties that can be exploited for applications in solving challenges in biomedical engineering.

Effect of plasma ion immersion implantation on physiochemical and biological properties of silk towards creating a versatile biomaterial platform

Silk biomaterials are widely used in tissue engineering applications due to their mechanical tuneability, processability and low immunogenic response. However, due to the lack of cell binding sites, further modification is typically required to optimize silk biomaterials towards a specific biomedical application. Plasma immersion ion implantation (PIII) is a surface modification technique that can covalently attach a wide range of bioactive molecules onto silk surfaces to trigger desirable biological responses. However, the effect of PIII treatment on the surface and bulk properties of silk biomaterials remains largely unknown. Therefore, the aim of this study is to investigate PIII-treated silk (PIII-silk) biomaterials towards their use as a platform for biomedical applications. Silk films with or without PIII treatment were examined to determine changes to the surface and bulk properties, including the chemical, mechanical, degradation properties, and the in vivo immune response. PIII treatment of silk was found to alter surface chemistry with densification of the silk surface layer and the introduction of oxygen and nitrogen functional groups. This then resulted in a significant increase in surface stiffness but also led to minor changes in tensile properties of clinically relevant silk formats and minor differences in in vitro degradation properties. Following PIII treatment, there was a significant increase in HCAEC adhesion on PIII-silk compared to untreated silk but no significant differences in fibrous encapsulation and macrophage response when implanted in vivo in a subcutaneous mouse model. Together, these results show that PIII treatment of silk minimally compromises the bulk properties and can be used to promote cellular interactions as well as a means of reagent-free, covalent immobilization of biomolecules.

Controllable Nitric Oxide‐Delivering Platforms for Biomedical Applications

AbstractNitric oxide (NO) serves a multitude of functions in human physiology and pathology, and therapeutic NO‐releasing materials are vigorously developed for biomedical applications. Owing to its complex functions and its potential systemic effects, controllable NO release is desired for clinical applications. This review summarizes recent developments in the last five years in designing controllable NO‐delivering platforms for treating diseases such as cancer, bacterial infection, cardiovascular diseases, wounds, and eye diseases, with a focus on the most commonly used NO donors, includingN‐diazeniumdiolates,S‐nitrosothiols, arginine, andN‐nitrosoamines. The progress and success of NO delivery strategies are highlighted, and their limitations are also included. Moreover, the therapeutic mechanisms of NO in the diseases are summarized, along with the corresponding means of controlling NO release. Finally, the prospects and potential challenges regarding the development of NO gas therapy are described, with the hope of encouraging new research in this area.

Carbon dots: a novel platform for biomedical applications.

Carbon dots (CDs) are a recently synthesised class of carbon-based nanostructures known as zero-dimensional (0D) nanomaterials, which have drawn a great deal of attention owing to their distinctive features, which encompass optical properties (e.g., photoluminescence), ease of passivation, low cost, simple synthetic route, accessibility of precursors and other properties. These newly synthesised nano-sized materials can replace traditional semiconductor quantum dots, which exhibit significant toxicity drawbacks and higher cost. It is demonstrated that their involvement in diverse areas of chemical and bio-sensing, bio-imaging, drug delivery, photocatalysis, electrocatalysis and light-emitting devices consider them as flawless and potential candidates for biomedical application. In this review, we provide a classification of CDs within their extended families, an overview of the different methods of CDs preparation, especially from natural sources, i.e., environmentally friendly and their unique photoluminescence properties, thoroughly describing the peculiar aspects of their applications in the biomedical field, where we think they will thrive as the next generation of quantum emitters. We believe that this review covers a niche that was not reviewed by other similar publications.

Cytosolic Delivery of Single-Chain Polymer Nanoparticles.

Cytosolic delivery of therapeutic agents is key to improving their efficacy, as the therapeutics are primarily active in specific organelles. Single-chain polymer nanoparticles (SCNPs) are a promising nanocarrier platform in biomedical applications due to their unique size range of 5-20 nm, modularity, and ease of functionalization. However, cytosolic delivery of SCNPs remains challenging. Here, we report the synthesis of active ester-functional SCNPs of approximately 10 nm via intramolecular thiol-Michael addition cross-linking and their functionalization with increasing amounts of tertiary amines 0 to 60 mol % to obtain SCNPs with increasing positive surface charges. No significant cytotoxicity was detected in bEND.3 cells for the SCNPs, except when SCNPs with high amounts of tertiary amines were incubated over prolonged periods of time at high concentrations. Cellular uptake of the SCNPs was analyzed, presenting different uptake behavior depending on the degree of functionalization. Confocal microscopy revealed successful cytosolic delivery of SCNPs with high degrees of functionalization (45%, 60%), while SCNPs with low amounts (0% to 30%) of tertiary amines showed high degrees of colocalization with lysosomes. This work presents a strategy to direct the intracellular location of SCNPs by controlled surface modification to improve intracellular targeting for biomedical applications.

Liposomal formulations of oxybutynin and resiniferatoxin for the treatment of urinary diseases: improvement of drug tolerance upon intravesical.

The use of liposomes for drug release has demonstrated to be a promising therapeutic platform for biomedical applications. In this study, intravesical administration of OXI (1.5mM) and RTX (100nM) was used to compare histological changes caused in Wistar female rats by the drugs both unloaded and loaded in liposomes. After instillation of formulations by intravesical catheter, bladders were removed and histological analysis carried out at pre-determined time intervals over a period of 60days. Urinalysis was performed to verify the presence of infection and of liposomes. Results showed that RTX caused a higher bladder damage, with inflammatory reaction that reached all bladder layers. After 60days, RTX-treated group showed urothelial alterations, collagen replacement by fibrosis and also abdominal adherence, but not the OXI-treated group. At the end of the assay, the liposomal-treated groups showed a minimal inflammatory reaction and significantly increased bladder size. Moreover, urinalysis confirmed the presence of liposomes in rat urine. RTX promoted higher bladder damage than OXI. Intravesical administration of liposomal OXI or RTX formulations minimized inflammatory reaction, with an extended drug effect on bladders. After a single intravesical administration, liposomes were found in rat urine samples after 60days.

Electroanalytical detection of amlodipine in urine and pharmaceutical samples using Ag-Ce2(WO4)3@CNF nanocomposite-modified glassy carbon electrode

A novel, simple, and convenient electroanalytical method for the detection of Amlodipine (AMD) has been investigated via an electro-oxidation mechanism using silver-cerium tungstate decorated carbon nanofiber (Ag-Ce2(WO4)3@CNF) nanocomposite by differential pulse voltammetry (DPV) for the first time. Ag-doped Ce2(WO4)3 decorated CNF was constructed by using simple hydrothermal followed by ultrasonication methods. The synthesized ternary nanocomposite was characterized by using FT-IR, X-Ray Diffraction, Raman spectroscopy, SEM with EDX, and TEM analysis. The Ag-Ce2(WO4)3@CNF modified GCE shows an excellent electrocatalytic response towards the oxidation of AMD in 0.05 M of PBS (pH 7) compared to Ag and Ag-Ce2(WO4)3 modified electrodes. The AMD detection limit is found to be 0.712 nM with a linear range of 0.01–130 μM. The electrocatalytic property of the ternary nanocomposite of electrochemical sensing of AMD in different real samples (human urine and pharmaceutical drug) has been investigated and achieved tremendous recovery. The fabricated sensor also shows good selectivity, reproducibility, and long-time stability. Hence, this ternary nanocomposite could be open a new platform in biomedical applications.

Carbon Dots Based Nanoscale Covalent Organic Frameworks for Photodynamic Therapy

AbstractCovalent organic frameworks (COFs) have attracted much attention for various applications, while developing COFs with biomedical functions remains a big challenge. Most COFs are built purely from organic molecules, no carbon dots (CDs)‐based COFs have been exploited to date. In this work, diamine molecules p‐phenylenediamine and BODIPY are selected as model monomers to react with aldehyde‐containing CDs and construct nanoscale COFs, named CCOF‐1 and CCOF‐2, respectively. After the modification with poly(ethylene glycol) (PEG), the formed CCOF‐1@PEG and CCOF‐2@PEG are stable and well‐dispersible in aqueous media. The merits of CCOF‐2@PEG containing favorable physiological stability, good biocompatibility, and strong reactive oxygen species generation ability enable it to act as an excellent photodynamic therapy (PDT) agent for tumor treatment. The high PDT therapeutic efficiency for inhibiting cell proliferation and tumor growth was well shown by in vitro and in vivo experiments. This work demonstrates a new strategy for fabricating functional COF‐based platforms for biomedical applications.

(Invited) Carbon Nano Onions for Biomedical Applications

Carbon-based nanomaterials have emerged as platforms for biomedical applications because of their low toxicity and ability to be internalized by cells [1]. The development of imaging probes and drug delivery devices based on carbon nanomaterials for biomedical studies requires the understanding of their biological response as well as the efficient and safety exposition of the nanomaterial to the cell compartment where it is designed to operate.Multi-shell fullerenes, also known as carbon nano-onions (CNOs) are structured by concentric shells of carbon atoms and display several unique properties, such as a large surface area to volume ratio, low density and a graphitic multilayer morphology [2]. In my research group we have developed a versatile and robust approach for the functionalisation of CNOs, involving the facile introduction of a number of simple functionalities onto their surface. Our results have shown that chemical functionalization of the CNOs dramatically enhance their solubility and reduce their inflammatory properties in vitro and in vivo [3]. We reported the absence of adverse effects induced by CNOs on short and long term toxicity in Hydra [4] and in zebrafish [5] suggesting a reasonable degree of biosafety of this new class of nanomaterials. We have developed intracellular imaging systems based on CNOs functionalised with BODIPY derivatives [6], with special attention to the biologically important near-infra red (NIR) region [7] and pH dependent fluorescence on-off switching [8]. The on/off emission of the fluorescent CNOs is fast and reversible both in solution and in vitro, making this nanomaterial suitable as pH-dependent probes for diagnostic applications [8].We have also developed a synthetic multi-functionalisation strategy for the introduction of different functionalities (receptor targeting unit and imaging unit) onto the surface of the CNOs The modified CNOs display high brightness and photostability in aqueous solutions and their selective and rapid uptake in two different cancer cell lines without significant cytotoxicity is demonstrated. The localization of the functionalized CNOs in late-endosomes cell compartments is revealed by a correlative approach with confocal and transmission electron microscopy [9].To probe the possible applications of CNOs as a platform for therapeutic and diagnostic interventions on CNS diseases, we injected fluorescent CNOs in vivo in mice hippocampus. We analyzed ex vivo their diffusion within brain tissues and their cellular localization by confocal and electron microscopy. The subsequent fluorescent staining of hippocampal cells populations indicates they efficiently internalize the nanoparticles. Furthermore, the inflammatory potential of the CNOs injection was found comparable to sterile vehicle infusion, and it did not result in manifest neurophysiological and behavioral alterations of hippocampal-mediated functions [10]. These results encourage further development as brain disease-targeted diagnostics or therapeutics nanocarriers.

Development of Multifunctional Biopolymeric Auto-Fluorescent Micro- and Nanogels as a Platform for Biomedical Applications.

The emerging field of theranostics for advanced healthcare has raised the demand for effective and safe delivery systems consisting of therapeutics and diagnostics agents in a single monarchy. This requires the development of multi-functional bio-polymeric systems for efficient image-guided therapeutics. This study reports the development of size-controlled (micro-to-nano) auto-fluorescent biopolymeric hydrogel particles of chitosan and hydroxyethyl cellulose (HEC) synthesized using water-in-oil emulsion polymerization technique. Sustainable resource linseed oil-based polyol is introduced as an element of hydrophobicity with an aim to facilitate their ability to traverse the blood-brain barrier (BBB). These nanogels are demonstrated to have salient features such as biocompatibility, stability, high cellular uptake by a variety of host cells, and ability to transmigrate across an in vitro BBB model. Interestingly, these unique nanogel particles exhibited auto-fluorescence at a wide range of wavelengths 450–780 nm on excitation at 405 nm whereas excitation at 710 nm gives emission at 810 nm. In conclusion, this study proposes the developed bio-polymeric fluorescent micro- and nano- gels as a potential theranostic tool for central nervous system (CNS) drug delivery and image-guided therapy.

Bacterial outer membrane vesicles as a platform for biomedical applications: An update

Outer membrane vesicles (OMVs) are produced by Gram-negative bacteria both in vitro and in vivo. OMVs are nano-sized spherical vehicles formed by lipid bilayer membranes and contain multiple parent bacteria-derived components. Based on the presence of bacterial antigens, pathogen-associated molecular patterns (PAMPs), adhesins, various proteins and the vesicle structure, OMVs have been developed for biomedical applications as bacterial vaccines, adjuvants, cancer immunotherapy agents, drug delivery vehicles, and anti-bacteria adhesion agents. In this review, we analyze the contributions of the structure and composition of OMVs to their applications, summarize the methods used to isolate and characterize OMVs, and highlight recent progress and future perspectives of OMVs in biomedical applications.

Biogenic supported lipid bilayers as a tool to investigate nano-bio interfaces

Hypothesis: Extracellular Vesicles (EVs) are natural nanosized lipid vesicles involved in most intercellular communication pathways. Given their nature, they represent natural cell membrane models, with intermediate complexity between real and synthetic lipid membranes. Here we compare EVs-derived (EVSLB) and synthetic Supported Lipid Bilayers (SLBs) in the interaction with cationic superparamagnetic iron oxide nanoparticles (SPIONs). The aim is twofold: (i) exploit SPIONs as nanometric probes to investigate the features of EVSLBs as novel biogenic platforms; (ii) contribute at improving the knowledge on the behavior of SPIONs with biological interfaces. Experiments: Quartz Crystal Microbalance, X-ray Reflectivity, Grazing-incidence Small-angle X-ray Scattering, Atomic Force Microscopy, Confocal Microscopy data on SPIONs-EVSLB were systematically compared to those on SPIONs challenging synthetic SLBs, taken as references. Findings: The ensemble of experimental results highlights the much stronger interaction of SPIONs with EVSLBs with respect to synthetic SLBs. This evidence strongly supports the hypotheses on the peculiar structure of EVSLBs, with cushioned non-flat areas and extended exposed surface; in addition, it suggests that these features are relevant in the response of biogenic membranes to nano-objects. These findings contribute to the fundamental knowledge on EVSLBs, key for their development both as biomimetic membranes, or as platforms for biomedical applications.

Short to ultrashort peptide-based hydrogels as a platform for biomedical applications.

Short peptides have attracted significant attention from researchers in the past few years due to their easy design, synthesis and characterization, diverse functionalisation possibilities, low cost, possibility to make a large range of hierarchical nanostructures and most importantly their high biocompatibility and biodegradability. Generally, short peptides are also relatively more stable than their longer variants, non-immunogenic in nature and many of them self-assemble to provide an exciting range of nanostructures, including hydrogels. Thus, the development of short peptide-based hydrogels has become an area of intense investigation. Although these hydrogels have a water content of greater than 90%, they are surprisingly highly stable structures, and thus have been used for various biomedical applications, including cell therapeutics, drug delivery, tissue engineering and regeneration, contact lenses, biosensors, and wound healing, by different researchers. Herein, we review the progress of research in the rapidly expanding field of short to ultrashort peptide-based hydrogels and their possible applications. Special attention is paid to address and review this field with regard to the stability of peptide-based hydrogels, particularly to enzymatic degradation.

Glycogen as a Building Block for Advanced Biological Materials.

Biological nanoparticles found in living systems possess distinct molecular architectures and diverse functions. Glycogen is a unique biological polysaccharide nanoparticle fabricated by nature through a bottom-up approach. The biocatalytic synthesis of glycogen has evolved over time to form a nanometer-sized dendrimer-like structure (20-150 nm) with a highly branched surface and a dense core. This makes glycogen markedly different from other natural linear or branched polysaccharides and particularly attractive as a platform for biomedical applications. Glycogen is inherently biodegradable, nontoxic, and can be functionalized with diverse surface and internal motifs for enhanced biofunctional properties. Recently, there has been growing interest in glycogen as a natural alternative to synthetic polymers and nanoparticles in a range of applications. Herein, the recent literature on glycogen in the material-based sciences, including its use as a constituent in biodegradable hydrogels and fibers, drug delivery vectors, tumor targeting and penetrating nanoparticles, immunomodulators, vaccine adjuvants, and contrast agents, is reviewed. The various methods of chemical functionalization and physical assembly of glycogen nanoparticles into multicomponent nanodevices, which advance glycogen toward a functional therapeutic nanoparticle from nature and back again, are discussed in detail.

Plasmonic Nanoparticle-Interfaced Lipid Bilayer Membranes.

Plasmonic nanoparticles are widely exploited in diverse bioapplications ranging from therapeutics to biosensing and biocomputing because of their strong and tunable light-matter interactions, facile and versatile chemical/biological ligand modifications, and biocompatibility. With the rapid growth of nanobiotechnology, understanding dynamic interactions between nanoparticles and biological systems at the molecular or single-particle level is becoming increasingly important for interrogating biological systems with functional nanostructures and for developing nanoparticle-based biosensors and therapeutic agents. Therefore, significant efforts have been devoted to precisely design and create nano-bio interfaces by manipulating the nanoparticles' size, shape, and surface ligand interactions with complex biological systems to maximize their performance and avoid unwanted responses, such as their agglomeration and cytotoxicity. However, investigating physicochemical interactions at the nano-bio interfaces in a quantitative and controllable manner remains challenging, as the interfaces involve highly complex networks between nanoparticles, biomolecules, and cells across multiple scales, each with a myriad of different chemical and biological interactions. A lipid bilayer is a membrane made of two layers of lipid molecules that forms a barrier around cells and plays structural and functional roles in diverse biological processes because they incorporate and present functional molecules (such as membrane proteins) with lateral fluidity. Plasmonic nanoparticles conjugated on lipid membranes provide reliable analytical labels and functional moieties that allow for studying and manipulating interactions between nanoparticles and molecules with single-particle resolution; they also serve as efficient tools for applying optical, mechanical, and thermal stimuli to biological systems, which stem from plasmonic properties. Recently, new opportunities have emerged by interfacing nanoparticle-modified lipid bilayers (NLBs) with complex systems such as molecular circuits and living systems. In this Account, we briefly review how plasmonic properties can be beneficially harnessed on lipid bilayer membranes to investigate the structures and functions of cellular membranes and to develop new platforms for biomedical applications. In particular, we discuss the versatility of supported lipid bilayers (SLBs), which are planar lipid bilayers on hydrophilic substrates, as dynamic biomaterials that provide lateral fluidity and cell membrane-like environments. We then summarize our efforts to create a quantitative analytical platform utilizing nanoparticles as active building blocks and SLBs as integrative substrates. Through this bottom-up approach, various functionalized nanoparticles have been introduced onto lipid bilayers to render nanoparticle-nanoparticle, nanoparticle-lipid bilayer, and biomolecule-lipid bilayer interfaces programmable. Our system provides a new class of tools for studying thermodynamics and kinetics in complex networks of nanostructures and for realizing unique applications in biosensing and biocomputing.

Photo-crosslinked hollow capsules as platform for biomedical applications

Photo-crosslinked hollow capsules as platform for biomedical applications