Robust and Biocompatible Functionalization of ZnS Nanoparticles by Catechol-Bearing Poly(2-methyl-2-oxazoline)s.

Zinc sulfide (ZnS) nanoparticles (NPs) are particularly interesting materials for their electronic and luminescent properties. Unfortunately, their robust and stable functionalization and stabilization, especially in aqueous media, has represented a challenging and not yet completely accomplished task. In this work, we report the synthesis of colloidally stable, photoluminescent and biocompatible core-polymer shell ZnS and ZnS:Tb NPs by employing a water-in-oil miniemulsion (ME) process combined with surface functionalization via catechol-bearing poly-2-methyl-2-oxazoline (PMOXA) of various molar masses. The strong binding of catechol anchors to the metal cations of the ZnS surface, coupled with the high stability of PMOXA against chemical degradation, enable the formation of suspensions presenting excellent colloidal stability. This feature, combined with the assessed photoluminescence and biocompatibility, make these hybrid NPs suitable for optical bioimaging.

Cyclic Polymer Grafts That Lubricate and Protect Damaged Cartilage.

Tissue-reactive graft copolymers were designed to protect the cartilage against enzymatic degradation and restore its lubrication properties during the early stages of osteoarthritis (OA). The copolymers feature a poly(glutamic acid) (PGA) backbone bearing hydroxybenzaldehyde (HBA) functions and cyclic poly(2-methyl-2-oxazoline) (PMOXA) side chains. PGA-PMOXA-HBA species chemisorb on the degraded tissue via Schiff bases and expose the biopassive and lubricious PMOXA cyclic grafts at the interface. The smaller hydrodynamic radius by cyclic PMOXA side chains coupled to the intrinsic absence of chain ends generate denser and more lubricious films on cartilage when compared to those produced by copolymers bearing linear PMOXA. Topology effects demonstrate how the introduction of cyclic polymers within tissue-reactive copolymers substantially improve their tribological and biopassive properties, suggesting a plethora of possible applications for cyclic macromolecules in biomaterials formulations.

Chemical Design of Non-Ionic Polymer Brushes as Biointerfaces: Poly(2-oxazine)s Outperform Both Poly(2-oxazoline)s and PEG.

The era of poly(ethylene glycol) (PEG) brushes as a universal panacea for preventing non-specific protein adsorption and providing lubrication to surfaces is coming to an end. In the functionalization of medical devices and implants, in addition to preventing non-specific protein adsorption and cell adhesion, polymer-brush formulations are often required to generate highly lubricious films. Poly(2-alkyl-2-oxazoline) (PAOXA) brushes meet these requirements, and depending on their side-group composition, they can form films that match, and in some cases surpass, the bioinert and lubricious properties of PEG analogues. Poly(2-methyl-2-oxazine) (PMOZI) provides an additional enhancement of brush hydration and main-chain flexibility, leading to complete bioinertness and a further reduction in friction. These data redefine the combination of structural parameters necessary to design polymer-brush-based biointerfaces, identifying a novel, superior polymer formulation.

Percutaneous Intratumoral Immunoadjuvant Gel Increases the Abscopal Effect of Cryoablation for Checkpoint Inhibitor Resistant Cancer.

Percutaneous cryoablation is a common clinical therapy for metastatic and primary cancer. There are rare clinical reports of cryoablation inducing regression of distant metastases, known as the "abscopal" effect. Intratumoral immunoadjuvants may be able to augment the abscopal rate of cryoablation, but existing intratumoral therapies suffer from the need for frequent injections and inability to confirm target delivery, leading to poor clinical trial outcomes. To address these shortcomings, an injectable thermoresponsive gel-based controlled release formulation is developed for the FDA-approved Toll-like-receptor 7 (TLR7) agonist imiquimod ("Imigel") that forms a tumor-resident depot upon injection and contains a contrast agent for visualization under computed tomography (CT). The poly-lactic-co-glycolic acid-polyethylene glycol-poly-lactic-co-glycolic acid (PLGA-PEG-PLGA)-based amphiphilic copolymer gel's underlying micellar nature enables high drug concentration and a logarithmic release profile that is additive with the neo-antigen release from cryoablation, requiring only a single injection. Rheological testing demonstrated the thermoresponsive increase in viscosity at body temperature and radio-opacity via microCT. Its ability to significantly augment the abscopal rate of cryoablation is demonstrated in otherwise immunotherapy resistant metastatic tumors in two aggressive colorectal and breast cancer dual tumor models with an all or nothing response, responders generally demonstrating complete regression of bilateral tumors in 90-day survival studies.

Actively Triggerable Metals via Liquid Metal Embrittlement for Biomedical Applications.

Actively triggerable materials, which break down upon introduction of an exogenous stimulus, enable precise control over the lifetime of biomedical technologies, as well as adaptation to unforeseen circumstances, such as changes to an established treatment plan. Yet, most actively triggerable materials are low-strength polymers and hydrogels with limited long-term durability. By contrast, metals possess advantageous functional properties, including high mechanical strength and conductivity, that are desirable across several applications within biomedicine. To realize actively triggerable metals, a mechanism called liquid metal embrittlement is leveraged, in which certain liquid metals penetrate the grain boundaries of certain solid metals and cause them to dramatically weaken or disintegrate. In this work, it is demonstrated that eutectic gallium indium (EGaIn), a biocompatible alloy of gallium, can be formulated to reproducibly trigger the breakdown of aluminum within different physiologically relevant environments. The breakdown behavior of aluminum after triggering can further be readily controlled by manipulating its grain structure. Finally, three possible use cases of biomedical devices constructed from actively triggerable metals are demonstrated.

Bioplastics for a circular economy.

Bioplastics - typically plastics manufactured from bio-based polymers - stand to contribute to more sustainable commercial plastic life cycles as part of a circular economy, in which virgin polymers are made from renewable or recycled raw materials. Carbon-neutral energy is used for production and products are reused or recycled at their end of life (EOL). In this Review, we assess the advantages and challenges of bioplastics in transitioning towards a circular economy. Compared with fossil-based plastics, bio-based plastics can have a lower carbon footprint and exhibit advantageous materials properties; moreover, they can be compatible with existing recycling streams and some offer biodegradation as an EOL scenario if performed in controlled or predictable environments. However, these benefits can have trade-offs, including negative agricultural impacts, competition with food production, unclear EOL management and higher costs. Emerging chemical and biological methods can enable the 'upcycling' of increasing volumes of heterogeneous plastic and bioplastic waste into higher-quality materials. To guide converters and consumers in their purchasing choices, existing (bio)plastic identification standards and life cycle assessment guidelines need revision and homogenization. Furthermore, clear regulation and financial incentives remain essential to scale from niche polymers to large-scale bioplastic market applications with truly sustainable impact.

Image-guided intratumoral immunotherapy: Developing a clinically practical technology.

Immunotherapy has revolutionized the contemporary oncology landscape, with durable responses possible across a range of cancer types. However, the majority of cancer patients do not respond to immunotherapy due to numerous immunosuppressive barriers. Efforts to overcome these barriers and increase systemic immunotherapy efficacy have sparked interest in the local intratumoral delivery of immune stimulants to activate the local immune response and subsequently drive systemic tumor immunity. While clinical evaluation of many therapeutic candidates is ongoing, development is hindered by a lack of imaging confirmation of local delivery, insufficient intratumoral drug distribution, and a need for repeated injections. The use of polymeric drug delivery systems, which have been widely used as platforms for both image guidance and controlled drug release, holds promise for delivery of intratumoral immunoadjuvants and the development of an in situ cancer vaccine for patients with metastatic cancer. In this review, we explore the current state of the field for intratumoral delivery and methods for optimizing controlled drug release, as well as practical considerations for drug delivery design to be optimized for clinical image guided delivery particularly by CT and ultrasound.

Bottle-grade polyethylene furanoate from ring-opening polymerisation of cyclic oligomers.

Polyethylene furanoate (PEF) represents a promising renewable resource-based bioplastic as replacement for fossil-based polyethylene terephthalate (PET) with improved material properties. However, the synthesis of PEF through conventional polycondensation remains challenging, since the time-intensive reaction leads to degradation and undesired discolouration of the product. Here we show the successful rapid synthesis of bottle-grade PEF via ring-opening polymerisation (ROP) from cyclic PEF oligomers within minutes, thereby avoiding degradation and discolouration. The melting point of such mixture of cyclic oligomers lies around 370 °C, well above the degradation temperature of PEF (~329 °C). This challenge can be overcome, exploiting the self-plasticising effect of the forming polymer itself (which melts around 220 °C) by initiation in the presence of a high boiling, yet removable, and inert liquid plasticiser. This concept yields polymer grades required for bottle applications (Mn > 30 kg mol-1, conversion > 95%, colour-free products), and can be extended to other diffusion-limited polymer systems.

Enzymatically crosslinked poly(2-alkyl-2-oxazoline) networks for 3D cell culture.

Molecularly designed, random copolymer-bioconjugates based on poly(2-methyl-2-oxazoline) (PMOXA) and poly(2-ethyl-2-oxazoline) (PEOXA) are crosslinked in the presence of sortase A (SA) and human articular chondrocytes (hACs), to yield cellularized polymer networks. Their gelation kinetics and mechanical properties are finely tuned by varying the concentration of SA, while a cell viability >90% is achieved after several weeks of culture, even in the absence of any cell-adhesive cue.

Surface Density Variation within Cyclic Polymer Brushes Reveals Topology Effects on Their Nanotribological and Biopassive Properties.

While topology effects by cyclic polymers in solution and melts are well-known, their translation into the interfacial properties of polymer "brushes" provides new opportunities to impart enhanced surface lubricity and biopassivity to inorganic surfaces, above and beyond that expected for linear analogues of identical composition. The impact of polymer topology on the nanotribological and protein-resistance properties of polymer brushes is revealed by studying linear and cyclic poly(2-ethyl-2-oxazoline) (PEOXA) grafts presenting a broad range of surface densities and while shearing them alternatively against an identical brush or a bare inorganic surface. The intramolecular constraints introduced by the cyclization provide a valuable increment in both steric stabilization and load-bearing capacity for cyclic brushes. Moreover, the intrinsic absence of chain ends within cyclic adsorbates hinders interpenetration between opposing brushes, as they are slid over each other, leading to a reduction in the friction coefficient (µ) at higher pressures, a phenomenon not observed for linear grafts. The application of cyclic polymers for the modification of inorganic surfaces generates films that outperform both the nanotribological and biopassive properties of linear brushes, significantly expanding the design possibilities for synthetic biointerfaces.