Tuning the Functionality of Self-Assembled 2D Platelets in the Third Dimension.

The decoration of 2D nanostructures using heteroepitaxial growth is of great importance to achieve functional assemblies employed in biomedical, electrical, and mechanical applications. Although the functionalization of polymers before self-assembly has been investigated, the exploration of direct surface modification in the third dimension from 2D nanostructures has, to date, been unexplored. Here, we used living crystallization-driven self-assembly to fabricate poly(ε-caprolactone)-based 2D platelets with controlled size. Importantly, surface modification of the platelets in the third dimension was achieved by using functional monomers and light-induced polymerization. This method allows us to selectively regulate the height and fluorescence properties of the nanostructures. Using this approach, we gained unprecedented spatial control over the surface functionality in the specific region of complex 2D platelets.

Self-Healing Hydrogel Scaffolds through PET-RAFT Polymerization in Cellular Environment.

Photo electron/energy transfer-reversible addition-fragmentation chain transfer (PET-RAFT) has emerged as a powerful reversible-deactivation radical polymerization technique, enabling oxygen-tolerant polymerizations with exquisite spatiotemporal control through irradiation with visible light. In contrast to traditional free radical photo-polymerization, which often requires the use of DNA-damaging UV irradiation, PET-RAFT offers a more cytocompatible alternative for the preparation of polymeric materials in cell culture environments. Herein, we report the use of PET-RAFT for the fabrication of self-healing hydrogels using commercially available monomers, reaching high monomer conversions and cell encapsulation efficiencies. Our hydrogels showed the expected rheological and mechanical properties for the systems considered, together with excellent cytocompatibility and spatiotemporal control over the polymerization process. Moreover, hydrogels prepared through this method could be cut and healed again by simply adding further monomer and irradiating the system with visible light, even in the presence of mammalian cells. This study demonstrates for the first time the potential of PET-RAFT polymerization as a viable methodology for the synthesis of self-healing hydrogel scaffolds for cell encapsulation.

Uniform segmented platelet micelles with compositionally distinct and selectively degradable cores.

The creation of nanoparticles with controlled and uniform dimensions and spatially defined functionality is a key challenge. The recently developed living crystallization-driven self-assembly (CDSA) method has emerged as a promising route to one-dimensional (1D) and 2D core-shell micellar assemblies by seeded growth of polymeric and molecular amphiphiles. However, the general limitation of the epitaxial growth process to a single core-forming chemistry is an important obstacle to the creation of complex nanoparticles with segmented cores of spatially varied composition that can be subsequently exploited in selective transformations or responses to external stimuli. Here we report the successful use of a seeded growth approach that operates for a variety of different crystallizable polylactone homopolymer/block copolymer blend combinations to access 2D platelet micelles with compositionally distinct segmented cores. To illustrate the utility of controlling internal core chemistry, we demonstrate spatially selective hydrolytic degradation of the 2D platelets-a result that may be of interest for the design of complex stimuli-responsive particles for programmed-release and cargo-delivery applications.

Enhanced drug delivery to cancer cells through a pH-sensitive polycarbonate platform.

Polymer-drug conjugates are widely investigated to enhance the selectivity of therapeutic drugs to cancer cells, as well as increase circulation lifetime and solubility of poorly soluble drugs. In order to direct these structures selectively to cancer cells, targeting agents are often conjugated to the nanoparticle surface as a strategy to limit drug accumulation in non-cancerous cells and therefore reduce systemic toxicity. Here, we report a simple procedure to generate biodegradable polycarbonate graft copolymer nanoparticles that allows for highly efficient conjugation and intracellular release of S-(+)-camptothecin, a topoisomerase I inhibitor widely used in cancer therapy. The drug-polymer conjugate showed strong efficacy in inhibiting cell proliferation across a range of cancer cell lines over non-cancerous phenotypes, as a consequence of the increased intracellular accumulation and subsequent drug release specifically in cancer cells. The enhanced drug delivery towards cancer cells in vitro demonstrates the potential of this platform for selective treatments without the addition of targeting ligands.

Ultra-Tough Elastomers from Stereochemistry-Directed Hydrogen Bonding in Isosorbide-Based Polymers.

The remarkable elasticity and tensile strength found in natural elastomers are challenging to mimic. Synthetic elastomers typically feature covalently cross-linked networks (rubbers), but this hinders their reprocessability. Physical cross-linking via hydrogen bonding or ordered crystallite domains can afford reprocessable elastomers, but often at the cost of performance. Herein, we report the synthesis of ultra-tough, reprocessable elastomers based on linear alternating polymers. The incorporation of a rigid isohexide adjacent to urethane moieties affords elastomers with exceptional strain hardening, strain rate dependent behavior, and high optical clarity. Distinct differences were observed between isomannide and isosorbide-based elastomers where the latter displays superior tensile strength and strain recovery. These phenomena are attributed to the regiochemical irregularities in the polymers arising from their distinct stereochemistry and respective inter-chain hydrogen bonding.

Crystallization-Induced Gelling as a Method to 4D Print Low-Water-Content Non-isocyanate Polyurethane Hydrogels.

The use of three-dimensional (3D) printable hydrogels for biomedical applications has attracted considerable attention as a consequence of the ability to precisely define the morphology of the printed object, allowing patients' needs to be targeted. However, the majority of hydrogels do not possess suitable mechanical properties to fulfill an adequate rheological profile for printability, and hence, 3D printing of cross-linked networks is challenging and normally requires postprinting modifications to obtain the desired scaffolds. In this work, we took advantage of the crystallization process of poly(ethylene glycol) to print non-isocyanate poly(hydroxyurethane) hydrogels with tunable mechanical properties. As a consequence of the crystallization process, the hydrogel modulus can be tuned up to 3 orders of magnitude upon heating up to 40 °C, offering an interesting strategy to directly 3D-print hydrogels without the need of postprinting cross-linking. Moreover, the absence of any toxicity makes these materials ideal candidates for biomedical applications.

Cyanine-5-Driven Behaviours of Hyperbranched Polymers Designed for Therapeutic Delivery Are Cell-Type Specific and Correlated with Polar Lipid Distribution in Membranes.

The ability to predict the behaviour of polymeric nanomedicines can often be obfuscated by subtle modifications to the corona structure, such as incorporation of fluorophores or other entities. However, these interactions provide an intriguing insight into how selection of molecular components in multifunctional nanomedicines contributes to the overall biological fate of such materials. Here, we detail the internalisation behaviours of polymeric nanomedicines across a suite of cell types and extrapolate data for distinguishing the underlying mechanics of cyanine-5-driven interactions as they pertain to uptake and endosomal escape. By correlating the variance of rate kinetics with endosomal escape efficiency and endogenous lipid polarity, we identify that observed cell-type dependencies correspond with an underlying susceptibility to dye-mediated effects and nanomedicine accumulation within polar vesicles. Further, our results infer that the ability to translocate endosomal membranes may be improved in certain cell types, suggesting a potential role for diagnostic moieties in trafficking of drug-loaded nanocarriers.

4D polycarbonates via stereolithography as scaffolds for soft tissue repair.

3D printing has emerged as one of the most promising tools to overcome the processing and morphological limitations of traditional tissue engineering scaffold design. However, there is a need for improved minimally invasive, void-filling materials to provide mechanical support, biocompatibility, and surface erosion characteristics to ensure consistent tissue support during the healing process. Herein, soft, elastomeric aliphatic polycarbonate-based materials were designed to undergo photopolymerization into supportive soft tissue engineering scaffolds. The 4D nature of the printed scaffolds is manifested in their shape memory properties, which allows them to fill model soft tissue voids without deforming the surrounding material. In vivo, adipocyte lobules were found to infiltrate the surface-eroding scaffold within 2 months, and neovascularization was observed over the same time. Notably, reduced collagen capsule thickness indicates that these scaffolds are highly promising for adipose tissue engineering and repair.

Thermally-induced hyperbranching of bromine-containing polyesters by insertion of in situ generated chain-end carbenes.

Hyperbranched, biodegradable PCL-based polymers are obtained through a random but invasive migration of an in situ generated carbene end group which is unmasked via the thermolysis of its precursor diazirine moiety. These hyperbranched cores are used as macroinitiators for 'grafting-from' polymerisation using controlled radical polymerisation to achieve amphiphilic copolymers which can subsequently be self-assembled into spherical core-shell micelles.

Aliphatic Polycarbonates from Cyclic Carbonate Monomers and Their Application as Biomaterials.

Aliphatic polycarbonates have gained increased attention as biomaterials largely owing to their biocompatibility and tunable degradation. Moreover, the ability to introduce functional handles in the polymer backbone through careful design of cyclic carbonate monomers or copolymerization with other biodegradable polymers has significantly contributed to the interest in exploiting this class of materials for biomedical applications. Such investigations have enabled their utility to be expanded to a wide variety of applications in the biomedical field, from drug delivery to tissue regeneration and the design of vascular grafts. Herein, we review the synthesis, degradation, and studies into biomedical applications of aliphatic polycarbonates obtained by ring-opening polymerization of cyclic carbonate monomers (ring sizes between 6 and 8). While all synthetic methods will be covered, particular emphasis will be given to materials that have been exploited for therapeutic applications in vitro and in vivo.

Concomitant control of mechanical properties and degradation in resorbable elastomer-like materials using stereochemistry and stoichiometry for soft tissue engineering.

Complex biological tissues are highly viscoelastic and dynamic. Efforts to repair or replace cartilage, tendon, muscle, and vasculature using materials that facilitate repair and regeneration have been ongoing for decades. However, materials that possess the mechanical, chemical, and resorption characteristics necessary to recapitulate these tissues have been difficult to mimic using synthetic resorbable biomaterials. Herein, we report a series of resorbable elastomer-like materials that are compositionally identical and possess varying ratios of cis:trans double bonds in the backbone. These features afford concomitant control over the mechanical and surface eroding degradation properties of these materials. We show the materials can be functionalized post-polymerization with bioactive species and enhance cell adhesion. Furthermore, an in vivo rat model demonstrates that degradation and resorption are dependent on succinate stoichiometry in the elastomers and the results show limited inflammation highlighting their potential for use in soft tissue regeneration and drug delivery.

Selective Chemical Upcycling of Mixed Plastics Guided by a Thermally Stable Organocatalyst.

Chemical recycling of plastic waste represents a greener alternative to landfill and incineration, and potentially offers a solution to the environmental consequences of increased plastic waste. Most plastics that are widely used today are designed for durability, hence currently available depolymerisation methods typically require harsh conditions and when applied to blended and mixed plastic feeds generate a mixture of products. Herein, we demonstrate that the energetic differences for the glycolysis of BPA-PC and PET in the presence of a protic ionic salt TBD:MSA catalyst enables the selective and sequential depolymerisation of these two commonly employed polymers. Employing the same procedure, functionalised cyclic carbonates can be obtained from both mixed plastic wastes and industrial polymer blend. This methodology demonstrates that the concept of catalytic depolymerisation offers great potential for selective polymer recycling and also presents plastic waste as a "greener" alternative feedstock for the synthesis of high added value molecules.

Organocatalytic Synthesis of Alkyne-Functional Aliphatic Polycarbonates via Ring-Opening Polymerization of an Eight-Membered-N-Cyclic Carbonate.

The synthesis of well-defined propargyl-functional aliphatic polycarbonates is achieved via the organocatalytic ring-opening polymerization of prop-2-yn-1-yl 2-oxo-1,3,6-dioxazocane-6-carboxylate (P-8NC) using a wide variety of commercially available or readily made, shelf-stable organocatalysts. The resulting homopolymers show low dispersities and end-group fidelity, with the versatility of the system being demonstrated by the synthesis of telechelic copolymers and block copolymers with molar mass up to 40 kDa.

Synthesis and applications of anisotropic nanoparticles with precisely defined dimensions.

Shape and size play powerful roles in determining the properties of a material; controlling these aspects with precision is therefore an important, fundamental goal of the chemical sciences. In particular, the introduction of shape anisotropy at the nanoscale has emerged as a potent way to access new properties and functionality, enabling the exploration of complex nanomaterials across a range of applications. Recent advances in DNA and protein nanotechnology, inorganic crystallization techniques, and precision polymer self-assembly are now enabling unprecedented control over the synthesis of anisotropic nanoparticles with a variety of shapes, encompassing one-dimensional rods, dumbbells and wires, two-dimensional and three-dimensional platelets, rings, polyhedra, stars, and more. This has, in turn, enabled much progress to be made in our understanding of how anisotropy and particle dimensions can be tuned to produce materials with unique and optimized properties. In this Review, we bring these recent developments together to critically appraise the different methods for the bottom-up synthesis of anisotropic nanoparticles enabling exquisite control over morphology and dimensions. We highlight the unique properties of these materials in arenas as diverse as electron transport and biological processing, illustrating how they can be leveraged to produce devices and materials with otherwise inaccessible functionality. By making size and shape our focus, we aim to identify potential synergies between different disciplines and produce a road map for future research in this crucial area.

Engineering the Mammalian Cell Surface with Synthetic Polymers: Strategies and Applications.

Manipulating the surface of living cells represents a powerful tool by which to control cell behavior and provides a unique strategy to modulate cellular function and cell-cell interactions. Recent progress in this area has seen the development of robust and elegant approaches to selectively decorate the cell surface, leading to unprecedented advances in cellular manipulation and cell-based therapies. Despite some impressive in vitro results, several obstacles remain to the broader application of some of these strategies, including their limited translation in vivo. In this review, the leading techniques used to introduce polymers at the plasma membrane of mammalian cells are discussed, focusing on strategies that generate a stable and homogeneous distribution of polymeric chains at the cell surface. Application of these strategies to control cell behavior and deliver cell-based therapies to targeted tissues are highlighted.

Elastomeric polyamide biomaterials with stereochemically tuneable mechanical properties and shape memory.

Biocompatible polymers are widely used in tissue engineering and biomedical device applications. However, few biomaterials are suitable for use as long-term implants and these examples usually possess limited property scope, can be difficult to process, and are non-responsive to external stimuli. Here, we report a class of easily processable polyamides with stereocontrolled mechanical properties and high-fidelity shape memory behaviour. We synthesise these materials using the efficient nucleophilic thiol-yne reaction between a dipropiolamide and dithiol to yield an α,ß - unsaturated carbonyl moiety along the polymer backbone. By rationally exploiting reaction conditions, the alkene stereochemistry is modulated between 35-82% cis content and the stereochemistry dictates the bulk material properties such as tensile strength, modulus, and glass transition. Further access to materials possessing a broader range of thermal and mechanical properties is accomplished by polymerising a variety of commercially available dithiols with the dipropiolamide monomer.

Manipulating the fluorescence lifetime at the sub-cellular scale via photo-switchable barcoding.

Fluorescent barcoding is a pivotal technique for the investigation of the microscale world, from information storage to the monitoring of dynamic biochemical processes. Using fluorescence lifetime as the readout modality offers more reproducible and quantitative outputs compared to conventional fluorescent barcoding, being independent of sample concentration and measurement methods. However, the use of fluorescence lifetime in this area has been limited by the lack of strategies that provide spatiotemporal manipulation of the coding process. In this study, we design a two-component photo-switchable nanogel that exhibits variable fluorescence lifetime upon photoisomerization-induced energy transfer processes through light irradiation. This remotely manipulated fluorescence lifetime property could be visually mapped using fluorescence lifetime imaging microscopy (FLIM), allowing selective storage and display of information at the microscale. Most importantly, the reversibility of this system further provides a strategy for minimizing the background influence in fluorescence lifetime imaging of live cells and sub-cellular organelles.

Exploiting the role of nanoparticle shape in enhancing hydrogel adhesive and mechanical properties.

The ability to control nanostructure shape and dimensions presents opportunities to design materials in which their macroscopic properties are dependent upon the nature of the nanoparticle. Although particle morphology has been recognized as a crucial parameter, the exploitation of the potential shape-dependent properties has, to date, been limited. Herein, we demonstrate that nanoparticle shape is a critical consideration in the determination of nanocomposite hydrogel properties. Using translationally relevant calcium-alginate hydrogels, we show that the use of poly(L-lactide)-based nanoparticles with platelet morphology as an adhesive results in a significant enhancement of adhesion over nanoparticle glues comprised of spherical or cylindrical micelles. Furthermore, gel nanocomposites containing platelets showed an enhanced resistance to breaking under strain compared to their spherical and cylindrical counterparts. This study opens the doors to a change in direction in the field of gel nanocomposites, where nanoparticle shape plays an important role in tuning mechanical properties.

3D Printing for the Clinic: Examining Contemporary Polymeric Biomaterials and Their Clinical Utility.

The advent of additive manufacturing offered the potential to revolutionize clinical medicine, particularly with patient-specific implants across a range of tissue types. However, to date, there are very few examples of polymers being used for additive processes in clinical settings. The state of the art with regards to 3D printable polymeric materials being exploited to produce novel clinically relevant implants is discussed here. We focus on the recent advances in the development of implantable, polymeric medical devices and tissue scaffolds without diverging extensively into bioprinting. By introducing the major 3D printing techniques along with current advancements in biomaterials, we hope to provide insight into how these fields may continue to advance while simultaneously reviewing the ongoing work in the field.