Biomacromolecules最新文献

Silk fibroin hydrogels are a promising platform for tissue engineering due to their biocompatibility and tunability, yet efficient cell recovery from gels remains a challenge. This work synthesizes reversible hydrogels by electrostatically-crosslinking carboxylated silk with linear and branched polyamine. Solvent choice (water, saline, or medium) and protein concentration impacted gel stiffness, mesh size, degradability, and function as an in vitro culture substrate. Hydrogels flowed as a liquid and recovered their viscoelastic properties when cycled under shear. Unlike enzymatically-crosslinked silk hydrogels, β-sheet content did not significantly increase during culture. Encapsulated mesenchymal stem cells proliferated, and live cells were recovered with high efficiency (>90%) by disrupting gels with shear. Lower protein concentrations resulted in hydrogels with lower stiffness, larger mesh size, and increased cell recovery. Electrostatic crosslinking of carboxylated fibroin is a viable route to silk hydrogels that permit encapsulation and subsequent retrieval of live stem cells for regenerative engineering applications.

The limited efficacy of cancer immunotherapy arises not only from insufficient immune activation, but more fundamentally from the absence of a systems-level strategy to coordinate the anti-cancer immunity cycle. Here, a poly(amino acid)−metal coordination nanoplatform comprising methoxy poly(ethylene glycol)−poly(glutamic acid), manganese ion (Mn²⁺), and quercetin (Quer) is engineered to orchestrate the cancer−immunity cycle dynamically. Mn²⁺-mediated Fenton-like reaction induces immunogenic cell death and fosters immune-activating tumor microenvironments (TMEs), as supported by a 1.7-fold increase in dendritic cell maturation and a 2.1-fold enhancement in cytotoxic T lymphocytes. Quer remodels the TMEs by reducing collagen deposition and inhibiting the activation of cancer-associated fibroblasts (CAFs), increasing T cell infiltration by 2.8-fold and downregulating programmed death-ligand 1 (PD-L1). Collectively, this platform functions as a coordinated immune cascade that amplifies anti-cancer immunity, achieving a 3.3-fold increase in tumor growth inhibition. This study shifts cancer immunotherapy from static intervention to programmable immune engineering, offering a strategy to overcome therapeutic barriers.

The clinical efficacy of dexamethasone (DEX) in ocular therapy remains limited by its low aqueous solubility and restricted epithelial permeability. To address these limitations, we developed high-capacity micellar formulations by a modified thin-film hydration method utilizing two poly(2-oxazoline) (POx)-based ABA triblock copolymers (A-pBuOx-A and A-pPentOx-A). We achieved drug loading capacities of up to 33 wt.%. The DEX loaded nanoformulations were characterized by differential scanning calorimetry and powder X-ray diffraction confirming the amorphous nature of DEX in lyophilized formulations. The micelles had a hydrodynamic diameter of D_h ≈ 18−24 nm. Both polymers were well tolerated and did not show any toxicity in primary human conjunctival fibroblasts and epithelial cells up to 50 g/L. Furthermore, the A-pBuOx-A/DEX formulation increased the apparent permeability of DEX approximately 12.2-fold across a primary human conjunctival epithelial barrier compared with Dexa EDO, without evidence of compromised barrier integrity or cell viability. These findings establish the POx polymer platform as a promising approach for enhancing epithelial delivery of poorly water-soluble ophthalmic drugs.

The one-pot synthesis and electrospinning of cellulose derivatives bearing pseudo-peptide pendants, which are expected to serve as novel chiral recognition materials, are reported. Ugi four-component reactions (U-4CRs) involving carboxymethyl cellulose (CMC), formaldehyde, a glycine-based isocyanide (ethyl isocyanoacetate), and six different amino acid methyl esters as the carboxylic acid, aldehyde, isocyanide, and amine components, respectively, were employed to introduce pseudo-peptide pendants onto the cellulose backbone. The reactions proceeded successfully under weakly acidic conditions (pH 4), yielding derivatives with degrees of substitution (DSs) of 0.37−0.44, whereas reactions at pH 1−3 and 5 were hindered by competing side reactions. The derivatives were characterized by FTIR, NMR, size-exclusion chromatography, and elemental analysis. Furthermore, they were successfully electrospun using poly(ethylene oxide) as a carrier polymer, producing uniform and continuous nanofibers. These results demonstrate the feasibility of combining U−4CR with electrospinning to fabricate functional cellulose-based nanofibrous materials for potential chiral recognition applications.

Electrospun fibers of polyhydroxyalkanoate (PHA), blended with PCL or PBS, were loaded with linezolid (LIN) to investigate induced morphological evolution, crystallization, and strain-induced deformation micromechanics. Up to the optimal nucleating concentration of 2 wt %, LIN was fully encapsulated, increasing PCL crystallinity from 33% to 72% and PHA crystallization enthalpy by 56%. At 3 wt %, PHA/PBS fibers developed discrete hollow, anisotropic LIN crystalline clusters through confinement-directed growth, whereas PHA/PCL fibers displayed a homogeneous nano-granular surface coating of LIN. Solid-state NMR revealed closer segmental interactions in PHA/PBS and moderate phase separation in PHA/PCL. In situ tensile SAXS and SEM disclosed brittle craze-to-crack fracture in PHA/PBS−LIN fibers but semi-ductile deformation in PHA/PCL−LIN fibers, involving multiple crazes, necking, and the in situ generation of an internal nanofibrillar bridging network within the craze cavities. This morphology, formed by flow-induced and LIN-nucleated crystallization, modulates the deformation mechanism and supports the design of PHA antibiotic-loaded scaffolds with controlled release.

New thermoplastic nonisocyanate poly(hydroxyurethanes) (NIPUs) have been designed by polyaddition reactions of carvyl acetate dicarbonate (CADC) with a range of commercial diamines, yielding thermoplastic nonisocyanate poly(hydroxyurethanes) with moderate molecular weights and glass transition temperatures (T_g) ranging from −30.5 to 62 °C. Thermal curing of the Jeffamine-derived poly(hydroxyurethane) with the polyacrylate compound LAROMER LR 9000 resulted in the formation of sticky thermoset materials, showing potential for adhesive applications. In addition, curing of bis(glydycyl ether dicarbonate) (BGDC)/CADC blends with polyethylene imine (PEI) enables the formation of tailor-made NIPU thermosets with high stiffness, tensile strength, and low elongation at break.

This review summarizes recent progress and applications of radical polymerization within cellular microenvironment. It starts with the evolution of synthetic polymers in biomedical applications, from early non-degradable and biodegradable materials to advanced smart responsive systems. The fundamental principles of radical polymerization are introduced, followed by a systematic classification of strategies employed in cellular settings, including thermal decomposition initiation, photoinitiation, intracellular environment-triggered polymerization, and controlled radical polymerization techniques such as atom transfer radical polymerization (ATRP) and reversible addition−fragmentation chain transfer polymerization (RAFT). This article highlights key innovations in cell surface engineering, intracellular imaging, drug delivery, and cancer therapy, with an emphasis on strategies that leverage cellular metabolism or disease-specific microenvironments for endogenous polymerization initiation. Current challenges, including spatiotemporal control, biocompatibility, and oxygen tolerance, are critically discussed, along with potential solutions. Finally, future perspectives on the application of radical polymerization in tissue engineering, immunomodulation, and precision medicine are presented.

A series of polymer nanocapsules were designed and synthesized for non-viral siRNA delivery to the central nervous system via intracerebroventricular injection. Various factors can contribute to superior diffusion profiles. In this study, we find that size, charge, and morphology play important roles. Further, we report an analysis that demonstrates the subtle effects that small chemical changes can have on whole-particle properties and the corresponding in vivo readouts. We use computational modeling to reveal previously unconsidered design criteria and hypothesize that cargo-templating considerations appear sufficient to connect differences in the internal structural organization to observed whole-particle properties. Collectively, computational and experimental findings work in synergy to deepen our molecular-level investigative capabilities to design and optimize nucleic acid delivery systems.

This study establishes a comprehensive platform for the axis-resolved analysis of anisotropic structure−property relationships in cellulose II. Using plate-like microcrystals synthesized via enzymatic polymerization, three-dimensionally oriented composite films were fabricated by combining a substrate-induced flat-on orientation with high-field magnetic alignment. X-ray diffraction revealed a highly ordered structure where the molecular chain axis (c-axis) is perpendicular to the substrate, and the [110] direction is aligned with the magnetic field. The type-B hydrogen-bonding network was indicated as a plausible structure for cellulose II upon integrating polarized Fourier transform infrared spectroscopy with geometrical analysis based on structural models. Mechanical testing combined with rule-of-mixtures analysis yielded an apparent modulus of 16.28 GPa along the magnetically selected χ₁ direction, comparable to the crystal modulus of 17.8 GPa calculated from the elastic tensor. This methodology provides a powerful approach for elucidating the structural and mechanical anisotropies of lamellar polymer crystals beyond cellulose.

Fully bio-based, self-expanding epoxy−acid foams were developed in this work. The strategy employs phosphoric acid (PHO) as a curing agent and expansion activator in a vegetable oil-based epoxy formulation. This approach relies on the exothermicity of the epoxy−acid reaction to simultaneously drive curing and gas generation, enabling a self-sustained foaming process under ambient conditions. Two formulations were studied: one containing only phosphoric acid (ESBOPHO) or a mixture with tartaric acid (ESBOTARPHO). While ESBOPHO rapidly reached temperatures of 80 °C, the hybrid system exhibited moderate exothermicity (around 35 °C), allowing for better processing control and morphological homogeneity. Compression molding and rheological measurements highlighted better thermal/hydrolytic stability and reprocessability for the hybrid system. Cone calorimetric tests revealed that tartaric acid reduced the peak heat release by 27% and total heat release by 49%, validating these foams as potential sustainable and safe insulators with a high carbonaceous residue content.