Polymers Interfacing with Biology

The development of various controlled radical polymerization techniques as well as site- and residue specific strategies to modify peptides/proteins with synthetic polymers have made polymer chemistry a powerful tool to address materials problems at the biology interface. This article will present recent examples for bioactive surface modification and polymer therapeutics; it will highlight the use of controlled radical polymerization techniques and bioconjugation strategies to develop surface coatings for regenerative medicine and diagnostics, respectively, polymer-based nanomedicines

Triazolinedione-'clicked' poly(phosphoester)s : systematic adjustment of thermal properties

The thermal properties of halogen-free flame retardant poly(phosphoester)s from acyclic diene metathesis polycondensation have been optimized by a systematic post-modification using 1,2,4-triazoline- 3,5-dione derivatives. The straightforward modification not only increased their glass transition temperatures significantly but also improved the thermal stability with respect to their char yields

Superbase-enabled anionic polymerization of poly(alkyl cyanoacrylate)s:achieving well-defined structures and controlled molar masses

Poly(alkyl cyanoacrylate)s (PACAs) find extensive use as adhesives in engineering and medicine. However, their high reactivity often leads to wide molar mass dispersity and uncontrolled chain-end functionalities. Achieving precise polymer structures is crucial, particularly for medical applications to prevent oligomer toxicity. The conventional anionic polymerization of cyanoacrylates initiated by water results in high molar mass dispersities (Ð) and low end-group functionalities. Nonetheless, under specific conditions, anionic polymerization holds the potential for controlling the molar mass and Ð of PACAs. Here, we demonstrate the synthesis of well-defined PACAs by employing minute quantities (1%) of superbases to activate a functional thiophenol (PhSH) initiator. This strategy enables the attainment of adjustable molecular weights (Mn &gt; 20 kg mol−1) and moderate dispersities (Ð &lt; 1.4) for homopolymers and block copolymers. The selective initiation by thiophenol is confirmed through 1H DOSY NMR analysis. Furthermore, the controlled homo- and copolymerization of ACA derivatives highlights the remarkable performance of the superbase in conjunction with PhSH.</p

The microstructure of polyphosphoesters controls polymer hydrolysis kinetics from minutes to years

The stability and degradation rates of polymers in aqueous media are critical factors for their biomedical applications, as they must remain intact for a specific period of time before degrading or degrading on-demand to prevent potential accumulation and harmful effects. Polyphosphoesters (PPEs) are highly compatible with biological systems, and the ester bonds in the backbone allow for hydrolytic degradation. In this study, we have demonstrated that the degradation rate of various PPEs can be precisely controlled by minor modifications to the side-chain and the binding pattern around the phosphorous center in the polymer backbone. We synthesized a systematic library of water-soluble PPEs using ring-opening polymerization, resulting in polyphosphates and in-chain or side-chain polyphosphonates. Specifically, we investigated the degradation rates of side-chain polyphosphonates with different side-chain structures (methyl, ethyl, allyl, iso- or n-propyl) at pH = 8 and pH = 11. Our results indicate that the degradation mechanism is influenced by the type and size of the side-chain, as well as the pH. At pH = 11, hydrophilicity is a key factor, while at pH = 8, electron density on the phosphorus is crucial, leading to a random chain scission or a backbiting mechanism. We also observed that changing the binding pattern of the phosphorus or incorporating additional “breaking points” allowed us to tune the half-life times of the polymer from less than a day to several years. This study highlights the versatile stability of water-soluble PPEs, making them a promising option for various applications that require different hydrolysis rates, such as tissue regrowth.</p

Main-chain water-soluble polyphosphoesters: multi-functional polymers as degradable PEG-alternatives for biomedical applications

Polyphosphoesters (PPEs) are a class of (bio)degradable polymers with high chemical versatility and functionality. In particular, water-soluble PPEs with the phosphoester group in the polymer backbone are currently discussed as a potential alternative to poly(ethylene glycol) (PEG). Ring-opening polymerization of typically 5-membered cyclic phosphoesters gives straightforward access to various well-defined PPEs. Several PPE candidates have proven their biocompatibility in vitro in terms of cytocompatibility, antifouling properties, “stealth effect”, degradability (hydrolytic and enzymatic), and some promising in vivo results in drug delivery vehicles. The possibility to control the properties with the appropriate tuning of the lateral chain makes PPEs especially appealing. This review summarizes recent developments of such PPEs for biomedical applications, e.g. in protein-polymer conjugates, hydrogels for tissue engineering, or nanocarriers for drug and gene delivery. We summarize the progress made over the years, highlighting the strengths and the shortcomings of PPEs for these applications to date. We critically evaluate the current state of the art, try to assess their potential and to predict future perspectives, shedding light on the pathway that needs to be followed to translate into clinics

Real-time ³¹P NMR reveals different gradient strengths in polyphosphoester copolymers as potential MRI-traceable nanomaterials

Polyphosphoesters (PPEs) are used in tissue engineering and drug delivery, as polyelectrolytes, and flame-retardants. Mostly polyphosphates have been investigated but copolymers involving different PPE subclasses have been rarely explored and the reactivity ratios of different cyclic phospholanes have not been reported. We synthesized binary and ternary PPE copolymers using cyclic comonomers, including side-chain phosphonates, phosphates, thiophosphate, and in-chain phosphonates, through organocatalyzed ring-opening copolymerization. Reactivity ratios were determined for all cases, including ternary PPE copolymers, using different nonterminal models. By combining different comonomers and organocatalysts, we created gradient copolymers with adjustable amphiphilicity and microstructure. Reactivity ratios ranging from 0.02 to 44 were observed for different comonomer sets. Statistical ring-opening copolymerization enabled the synthesis of amphiphilic gradient copolymers in a one-pot procedure, exhibiting tunable interfacial and magnetic resonance imaging (MRI) properties. These copolymers self-assembled in aqueous solutions, 31 P MRI imaging confirmed their potential as MRI-traceable nanostructures. This systematic study expands the possibilities of PPE-copolymers for drug delivery and theranostics.</p

Towards more homogeneous character in 3D printed photopolymers by the addition of nanofillers

The performance of 3D printed materials differs from that of fully cured polymer materials because of the presence of interfacial areas between consecutively joined layers. These interfaces result in an inhomogeneous character of the printed objects and is frequently reported as their main cause of failures. We noted that the presence of nanosilica particles strengthens the 3D printed layers of the polymer matrix by inducing its additional crosslinking. A model resin composed of poly (ethylene glycol) diacrylate (PEGDA) and nanosilica (Aerosil R972) is used for vat photopolymer 3D printing. Evolution of the interface properties at different nanosilica loadings is tracked by mapping its surface stiffness (Young's modulus mapping) using quantitative Atomic Force Microscopy (AFM). Our research demonstrates that incorporating 6% w/v nanosilica in the polyPEGDA matrix unifies its mechanical properties within the layer, leading to a substantial reduction of microscopic inhomogeneity in the final 3D printed materials.</p

Nanoscale Control of the Surface Functionality of Polymeric 2D Materials

Typically, 2D nanosheets have a homogeneous surface, making them a major challenge to structure. This study proposes a novel concept of 2D organic nanosheets with a heterogeneously functionalized surface. This work achieves this by consecutively crystallizing two precisely synthesized polymers with different functional groups in the polymer backbone in a two-step process. First, the core platelet is formed and then the second polymer is crystallized around it. As a result, the central area of the platelets has a different surface functionality than the periphery. This concept offers two advantages: the resulting polymeric 2D platelets are stable in dispersion, which simplifies further processing and makes both crystal surfaces accessible for subsequent functionalization. Additionally, a wide variety of polymers can be used, making the process and the choice of surface functionalization very flexible.</p