Microenvironment with NIR-Controlled ROS and Mechanical Tensions for Manipulating Cell Activities in Wound Healing.

The extracellular matrix (ECM) orchestrates cell behavior and tissue regeneration by modulating biochemical and mechanical signals. Manipulating cell-material interactions is crucial for leveraging biomaterials to regulate cell functions. Yet, integrating multiple cues in a single material remains a challenge. Here, near-infrared (NIR)-controlled multifunctional hydrogel platforms, named PIC/CM@NPs, are introduced to dictate fibroblast behavior during wound healing by tuning the matrix oxidative stress and mechanical tensions. PIC/CM@NPs are prepared through cell adhesion-medicated assembly of collagen-like polyisocyanide (PIC) polymers and cell-membrane-coated conjugated polymer nanoparticles (CM@NPs), which closely mimic the fibrous structure and nonlinear mechanics of ECM. Upon NIR stimulation, PIC/CM@NPs composites enhance fibroblast cell proliferation, migration, cytokine production, and myofibroblast activation, crucial for wound closure. Moreover, they exhibit effective and toxin removal antibacterial properties, reducing inflammation. This multifunctional approach accelerates healing by 95%, highlighting the importance of integrating biochemical and biophysical cues in the biomaterial design for advanced tissue regeneration.

The Preparation of Biomineralized PIC/HA Hybrid Composites with Strain-Stiffening and the Effect on MC3T3-E1 Cells.

The development of biomimetic extracellular matrix (ECM) with fibrous structure and complex nonlinear mechanics has been attracting intensive attention over the past decades both in material science and tissue engineering. Polyisocyanopeptide (PIC) hydrogels are a class of fully synthetic materials that can mimic biogels, such as fibrin and collagen, in nearly all aspects, particularly the micron-sized gel network and the strong strain-stiffening behavior in the biological regime. Here, a biomimetic PIC/hydroxyapatite (HA) hybrid composite through an enzymatic biomineralization strategy is constructed. HA biominerals grew on PIC bundles in situ catalyzed by the embedded alkaline phosphatase (ALP), which further crosslinked the gel networks and reinforced the mechanical property of PIC hydrogels. Significantly, PIC/HA composites exhibited ultra-responsive nonlinear mechanics with higher sensitivity to mechanical stress compared with those without biomineralization. As a consequence, the presence of HA can provide cell adhesion sites for PIC gels and induce osteogenic differentiation of pre-osteoblasts by virtue of the changes in mechanical properties. With these outstanding properties, therefore, PIC/HA composites present promising prospects in bone tissue engineering as biomimetic ECM.

Polyisocyanide hydrogels with tunable nonlinear elasticity mediate liver carcinoma cell functional response.

Hepatocellular carcinoma development is closely related to the changes in tissue mechanics induced by excess collagen deposition and crosslinking, which leads to liver fibrosis and malignant progression. The role of matrix stiffness has been widely assessed using various linearly elastic materials. However, the liver, like many soft tissues, also exhibits nonlinear elasticity by strain-stiffening, allowing cells to mechanically interact with their micromilieus which has attracted much attention in cellular processes recently. Here, we use a biomimetic hydrogel grafting of GRGDS peptide with tunable nonlinear mechanical properties, polyisocyanides (PIC), to investigate the influence of strain-stiffening on HepG2 liver cancer cell behavior by tuning PIC polymer length. Compared to short PIC polymer with lower critical stress, PIC hydrogels composed of long polymer with higher critical stress promote the motility and invasiveness of HepG2 cells, and induce more actin stress fibers and higher expression level of mechanotransducer YAP and its nuclear translocation. Strikingly, the expression of calcium-activated potassium channel KCa3.1, an important biomarker in hepatocellular carcinoma, is also affected by the mechanical property of PIC hydrogels. It was also shown that downregulating the KCa3.1 channel can be achieved by inhibiting the formation of actin fibers. Our findings imply that the strain-stiffening property of PIC hydrogels affects the expression of KCa3.1 potassium channel via mediating cytoskeletal stress fiber formation, and ultimately influences the liver carcinoma cell functional response. STATEMENT OF SIGNIFICANCE: The effect of nonlinear elasticity by strain-stiffening, is assessed in HepG2 liver cancer cell behavior by using a biomimetic hydrogel with tunable mechanical properties, polyisocyanides (PIC). PIC gels with higher critical stress promote the motility and invasiveness of HepG2 cells and induce upregulated expression levels of KCa3.1 potassium channel and YAP, but which can be suppressed by inhibiting the formation of actin fibers. Our findings imply that the strain-stiffening property of PIC gels influences the expression of KCa3.1 potassium channel via mediating cytoskeletal stress fiber formation and, ultimately affects the liver carcinoma cell functional response.

Preparation of environmentally friendly acrylic pressure-sensitive adhesives by bulk photopolymerization and their performance.

Polyacrylic pressure-sensitive adhesives (PSAs) based on butyl acrylate (BA), 2-hydroxyethyl acrylate (HEA), and acrylic acid (AA) were prepared by a bulk polymerization process triggered by a radical photoinitiator under UV irradiation and UV-crosslinking. 1,6-Hexanediol diacrylate (HDDA) with difunctional groups was introduced into the PSAs to modify semi-interpenetrating network structures. The effect of HDDA content on the pressure-sensitive performance was comprehensively tested. The viscosity of the prepolymer was measured by a rotational viscometer. Prepolymers obtained by a photoinduced process and UV crosslinking process were confirmed via Fourier transform infrared spectroscopy (FTIR). All double bonds participated in the copolymerization without any remaining monomers, which reflected the concept of green environmental protection. Gel content in the crosslinked portion was examined by Soxhlet extraction, whilst the soluble molecular weight of PSAs was characterized by gel permeation chromatography (GPC). The viscoelastic properties of polymer films were determined by dynamic mechanical analysis (DMA). The T g value and storage modulus (G') of the PSAs were enhanced with the addition of HDDA. Moreover, three fundamental adhesive properties, i.e. loop tack force, peel force and shear strength of PSAs, were measured. The results showed that UV crosslinking technology achieved a good balance of the three forces with excellent pressure-sensitive properties.