Biomacromolecules最新文献

Diabetes requires precise insulin management to maintain glycemic control and prevent severe complications. Glucose-responsive delivery systems envision an autonomous approach to improve insulin therapy. Here, a glucose-sensitive insulin delivery system comprising hyaluronic acid conjugated with a diboronate glucose binder as a carrier for diol-modified insulin is shown. This approach seeks improved precision in insulin delivery, leveraging bidentate glucose binding to achieve enhanced glucose affinity and specificity. Modification of insulin with a diol motif preserves its native conformation and function. These insulin formulations correct blood glucose in diabetic mice, including glucose-responsive function when subjected to a glucose challenge. However, the absence of secondary interactions, such as electrostatic complexation, ultimately limits the duration of function relative to that of previous platforms. Integrating complementary interactions alongside dynamic-covalent glucose binders therefore enhances the functional duration and therapeutic efficacy in the design of glucose-responsive polymeric carriers, offering design insights into the development of new carriers for glucose-responsive insulin delivery.

Nitric oxide (NO), known for its anticoagulant and antiproliferative effects, holds great promise in anticoagulation therapy. Copper-based metal–organic frameworks, such as CuBTTri, catalyze NO formation, but their impact on vascular cells requires further study. In this work, polydopamine, polyethylenimine, and CuBTTri were codeposited on titanium substrates. To enhance cytocompatibility, heparin-mimicking copolymers were incorporated. By adjusting CuBTTri content, NO release rates and cytotoxicity toward vascular cells were regulated. The heparin-mimicking copolymers improved the cytocompatibility with human umbilical vein endothelial cells, while NO released from CuBTTri inhibited the proliferation of human umbilical vein smooth muscle cells. By integrating NO-releasing CuBTTri with heparin-mimicking copolymers, we successfully developed a composite coating that selectively modulates vascular cell behavior.

Nitric oxide (NO), known for its anticoagulant and antiproliferative effects, holds great promise in anticoagulation therapy. Copper-based metal-organic frameworks, such as CuBTTri, catalyze NO formation, but their impact on vascular cells requires further study. In this work, polydopamine, polyethylenimine, and CuBTTri were codeposited on titanium substrates. To enhance cytocompatibility, heparin-mimicking copolymers were incorporated. By adjusting CuBTTri content, NO release rates and cytotoxicity toward vascular cells were regulated. The heparin-mimicking copolymers improved the cytocompatibility with human umbilical vein endothelial cells, while NO released from CuBTTri inhibited the proliferation of human umbilical vein smooth muscle cells. By integrating NO-releasing CuBTTri with heparin-mimicking copolymers, we successfully developed a composite coating that selectively modulates vascular cell behavior.

The use of biodegradable materials in bone plates offers remarkable advantages; however, their application in bone fixation is limited by their brittleness. Moreover, treatments tailored to patient conditions are needed in orthopedics. In this study, bone plates were fabricated with stereocomplex polylactic acid (scPLA) and the effects of poly(d-lactic acid) molecular weight and scPLA blending ratios were analyzed. Although modulus values of poly(l-lactic acid) (PLLA) and scPLA were similar, strain resistance improved at higher scPLA proportions. The enhanced elongation was owing to the presence of tie molecules within the scPLA as opposed to single PLA chains. The fabricated scPLA bone plates exhibited improved mechanical properties and transparency in the optical and near-infrared ranges. scPLA was characterized by a smaller crystallite size. These properties of scPLA combined with its biocompatibility indicate potential for various diagnostic and therapeutic orthopedic applications. Comparisons with commercial PLLA-based bone plates show no significant differences in in vivo bone-healing ability.

Complex coacervates have emerged as promising tissue adhesives due to their excellent wet adhesion and tunable properties. However, maintaining stable adhesion on soft, dynamic tissues remains challenging. In this study, the use of a bridging polymer was investigated to enhance the adhesive properties of a complex coacervate adhesive (CCA) composed of poly(allylamine hydrochloride) (pAH) and polysulfopropyl methacrylate (pSPMA). The CCA undergoes solidification as a result of a change in salt concentration, forming a robust adhesive under physiological conditions. Pretreatment with pAH, but not pSPMA, significantly improved adhesion energy on both model hydrogels and biological tissues by forming a polymer-rich bridging layer at the interface. The beneficial effect was driven by accumulation of pAH in superficial layers of both the CCA and the substrates. This enabled the CCA to withstand higher deformation before adhesive failure. These findings underscore the potential of bridging polymers to improve CCAs and other tissue adhesives for biomedical applications.

Complex coacervates have emerged as promising tissue adhesives due to their excellent wet adhesion and tunable properties. However, maintaining stable adhesion on soft, dynamic tissues remains challenging. In this study, the use of a bridging polymer was investigated to enhance the adhesive properties of a complex coacervate adhesive (CCA) composed of poly(allylamine hydrochloride) (pAH) and polysulfopropyl methacrylate (pSPMA). The CCA undergoes solidification as a result of a change in salt concentration, forming a robust adhesive under physiological conditions. Pretreatment with pAH, but not pSPMA, significantly improved adhesion energy on both model hydrogels and biological tissues by forming a polymer-rich bridging layer at the interface. The beneficial effect was driven by accumulation of pAH in superficial layers of both the CCA and the substrates. This enabled the CCA to withstand higher deformation before adhesive failure. These findings underscore the potential of bridging polymers to improve CCAs and other tissue adhesives for biomedical applications.

Freeze–drying bigels is a novel technique for developing functional materials for dermatological and cosmetic use, leveraging the benefits of two structured phases. This study optimized freeze–dried bigels composed of whey protein isolate (WPI)/sodium alginate/glycerin hydrogel and ethylcellulose (EC)/Span 80/sunflower oil oleogel at varying hydrogel/oleogel ratios. The materials showed swelling ratios from 50% to 255%, with higher values for a lower oleogel content and higher polymer concentration. The higher oleogel content extended the degradation from a few hours to 7 days. The polymer concentrations and hydrogel/oleogel ratios influenced Young’s modulus (1.25–3.7 MPa). Porosity varied from 35% to 58%, and density varied from 100 to 200 mg/mL. The residual moisture content (5% to 20%) increased with EC content and decreased with WPI and oleogel content. These findings underscore the role of polymer concentrations and phase ratios in tuning the physicochemical properties of freeze–dried gels, positioning them as promising biomaterials for skincare and cosmetic applications.

Protein biologics hold immense potential in therapeutic applications, but their ephemeral nature has hindered widespread application. The effects of different stressors on protein folding have long been studied, but whether these stressors induce protein unfolding through different pathways remains unclear. Here, we conduct all-atom molecular dynamics simulations to investigate the unfolding of bovine serum albumin (BSA) under three distinct stressors: high temperature, acidic pH, and shear stress. Our findings reveal that each stressor induces unique unfolding patterns in BSA, indicating stressor-specific unfolding pathways. Structural analyses show that high temperature significantly disrupts the protein’s secondary structure, while acidic pH causes alternations in the tertiary structure, leading to domain separation. Shear stress initially perturbs the tertiary structure, initiating structural rearrangements, which causes a loss of secondary structure similar to temperature. These distinct unfolding behaviors suggest that different stabilization strategies are required to enhance protein stability under different denaturation conditions.

Protein biologics hold immense potential in therapeutic applications, but their ephemeral nature has hindered widespread application. The effects of different stressors on protein folding have long been studied, but whether these stressors induce protein unfolding through different pathways remains unclear. Here, we conduct all-atom molecular dynamics simulations to investigate the unfolding of bovine serum albumin (BSA) under three distinct stressors: high temperature, acidic pH, and shear stress. Our findings reveal that each stressor induces unique unfolding patterns in BSA, indicating stressor-specific unfolding pathways. Structural analyses show that high temperature significantly disrupts the protein's secondary structure, while acidic pH causes alternations in the tertiary structure, leading to domain separation. Shear stress initially perturbs the tertiary structure, initiating structural rearrangements, which causes a loss of secondary structure similar to temperature. These distinct unfolding behaviors suggest that different stabilization strategies are required to enhance protein stability under different denaturation conditions.

Freeze-drying bigels is a novel technique for developing functional materials for dermatological and cosmetic use, leveraging the benefits of two structured phases. This study optimized freeze-dried bigels composed of whey protein isolate (WPI)/sodium alginate/glycerin hydrogel and ethylcellulose (EC)/Span 80/sunflower oil oleogel at varying hydrogel/oleogel ratios. The materials showed swelling ratios from 50% to 255%, with higher values for a lower oleogel content and higher polymer concentration. The higher oleogel content extended the degradation from a few hours to 7 days. The polymer concentrations and hydrogel/oleogel ratios influenced Young's modulus (1.25-3.7 MPa). Porosity varied from 35% to 58%, and density varied from 100 to 200 mg/mL. The residual moisture content (5% to 20%) increased with EC content and decreased with WPI and oleogel content. These findings underscore the role of polymer concentrations and phase ratios in tuning the physicochemical properties of freeze-dried gels, positioning them as promising biomaterials for skincare and cosmetic applications.