ACS Biomaterials Science & Engineering最新文献

Bioactive components, especially hydrophobic functional molecules, have inspired various nanobiotechnology approaches to stabilize and further realize their biological functions, particularly in vivo delivery. Desirable features of a delivery system for functional molecules should possess high biocompatibility, favorable encapsulation capacity, and simple fabrication processes without requiring chemical modification of the molecule itself. Herein, we report a facile and low-cost approach, based on tannic acid-polyethylene glycol (TA-PEG)-mediated assembly, for assembling citrus-derived nobiletin into nanoparticles (i.e., NTP NPs) under aqueous conditions. The resulting multifunctional spherical NPs with long-term stability and desirable encapsulation efficacy are mostly facilitated by hydrogen bonding and π interactions, as confirmed by in-depth spectroscopic analyses. Incorporating fluorophores into NTP NPs enables the visualization of intracellular transport and biodistribution at different time points, revealing that most of these NPs achieved enhanced cellular uptake and transport efficiency and prolonged intestinal retention, comparable to that of free nobiletin. This work provides a viable strategy for the rational design of hydrophobic functional molecule nanoparticle delivery platforms tailored for diverse biological applications.

Catheters are indispensable medical tools for accessing blood vessels, hollow organs, and body cavities to facilitate medication delivery and fluid drainage. However, they also serve as major entry points for bacterial contamination and trigger foreign body responses, necessitating locking strategies that are both bactericidal and biocompatible. This study introduces the first gel-based catheter lock, in contrast to conventional liquid locks. The gel is a poloxamer-based hydrogel formulated with 2-hydroxypropyl α-cyclodextrin (HP-αCD). HP-αCD forms supramolecular complexes with the poloxamer to enhance gelation and with the nitric oxide (NO) donor to modulate NO release kinetics. This thixotropic gel can be injected into the catheter lumen when the catheter is not in use and withdrawn when vascular access is needed. The gel matrix provides a physical barrier that slows bacterial migration and minimizes drug loss. Simultaneously, the released NO functions as a broad-spectrum antimicrobial agent, effectively preventing biofilm formation on both the internal and external surfaces of the catheter. The NO-releasing hydrogel also demonstrates excellent hemocompatibility and reduces clot adhesion. Together, the gel-based lock offers a promising strategy for more effective catheter maintenance and represents a new application of hydrogels.

Human hemoglobin (hHb) in the tense (T) quaternary state was copolymerized with human serum albumin (HSA) at various hHb:HSA mass fractions to form polymerized hHb-HSA Poly(hHb:HSA) conjugates as a potential next-generation hemoglobin-based oxygen carrier (HBOC). These conjugates were evaluated for molecular weight (M_W), hydrodynamic size, oxygen transport characteristics, heme and oxidative stability, as well as hemorheological and colloid osmotic pressure (COP) properties. Among the variants, Poly(hHb₇₅:HSA₂₅) achieved a high M_W (2024 ± 262 kDa), hydrodynamic diameter (29.6 ± 2.3 nm), yield (39 ± 1%), and batch mass (11.8 ± 0.2 g), closely matching PolyhHb₁₀₀. In comparison, Poly(hHb₅₀:HSA₅₀) exhibited a lower M_W (875 ± 84 kDa) and diameter (21.5 ± 1.9 nm), with a reduced yield (26 ± 4%) and batch mass (7.7 ± 1.3 g). Both formulations demonstrated rapid oxygen offloading (63.1 ± 0.5 and 59.0 ± 1.4 s^-1) and low oxygen affinity (P₅₀ = 49.04 ± 0.95 and 41.79 ± 0.81 mmHg), indicating effective oxygen delivery under moderate oxygen tensions. Although polymerization modestly elevated the auto-oxidation rate compared to the precursor hHb, the oxidative stability remained comparable between Poly(hHb₇₅:HSA₂₅) and Poly(hHb₅₀:HSA₅₀), suggesting that HSA incorporation does not significantly impact the rate of auto-oxidation. Both Poly(hHb₇₅:HSA₂₅) and Poly(hHb₅₀:HSA₅₀) reduced haptoglobin binding (0.005 and 0.004 μM^-1 s^-1) and heme release rates, reflecting enhanced heme retention and reduced oxidative risk. Both Poly(hHb₇₅:HSA₂₅) and Poly(hHb₅₀:HSA₅₀) exhibited similar zeta potentials (-23.2 ± 1.3 mV and -27.0 ± 1.7 mV respectively). Structural analyses confirmed the preserved α-helical content, thermal stability (69.5-70.9 °C), and retained intrinsic catalase activity of the two variants. Hemorheological and COP analyses further revealed that both Poly(hHb₇₅:HSA₂₅) and Poly(hHb₅₀:HSA₅₀) exhibited low COP, were hyperviscous solutions with shear-thinning behavior, and exhibited reversible red blood cell (RBC) aggregation at low shear rates. Therefore, both T-state Poly(hHb₇₅:HSA₂₅) and Poly(hHb₅₀:HSA₅₀) offer an optimal balance of oxygen delivery, oxidative resilience, manufacturability, shear-thinning behavior, making them strong candidates for further HBOC development.

Management of chronic wounds poses a significant challenge for medical teams worldwide, as it often requires prolonged hospitalization periods and frequently leaves sequelae, thereby becoming a public health problem. Furthermore, available medical treatments are usually ineffective for treating this type of injury; therefore, a survey for new treatments to achieve favorable outcomes is frequently sought. Among new treatment options for wound healing, the use of peptides extracted from the skin of Nile tilapia (Oreochromis niloticus) has shown favorable results. The objective of this work was to evaluate the evidence demonstrating the effectiveness of Nile tilapia skin peptides (NTSP) in modulating cellular and molecular mechanisms involved in the wound healing process in animal models. A systematic review and meta-analysis were performed using the PubMed, SciELO, Web of Science, and EMBASE databases. Articles from 2014 to 2024 were selected using a combination of keywords (tilapia skin) AND (wound healing) AND (peptides), along with synonyms, according to the MeSH criteria. A total of 378 studies were identified, of which 16 were deemed relevant based on the inclusion and exclusion criteria. According to the studies analyzed, NTSP delivery systems led to a decrease in the wound healing period, stimulated blood vessel formation, regulated and mediated anti- and pro-inflammatory cytokines, and controlled infection. Syrcle's scale was used to assess the risk of bias, which was determined to be low. Additionally, the results from the meta-analysis demonstrate statistical significance in the findings from experiments utilizing NTSP. It is particularly evident in relation to wound retraction, wound closure, inflammatory score, and angiogenesis, indicating that the use of NTSP affects cellular and molecular mechanisms that stimulate the wound-healing process. However, significant heterogeneity was observed among the studies, which is a limitation of the analysis. Therefore, further clinical trials and standardized protocols are necessary to better elucidate the effects of NTSP.

To investigate the effect of carbonate content on the corrosion resistance and osteoclastic resorbability of carbonate apatite (CAp) coatings for biodegradable Mg alloys, polarization, electrochemical impedance, and osteoclast precursor cell culture tests were conducted for CAp-coated pure Mg (Mg) and Mg-4Y-3RE (WE43) containing approximately 11, 17, and 18 wt % carbonate. In Hanks' solution, the polarization resistance (R_p) was higher than in a 0.9% NaCl solution, and the CAp coatings improved the R_p of Mg by 7 to 15 times. The R_p of CAp-coated Mg increased by approximately 1.5 times in a 0.9% NaCl solution and 2 times in Hanks' solution with increasing carbonate content, indicating a reduction in coating defects. For CAp-coated Mg, osteoclasts only survived on the higher carbonate content coating. For WE43, the coating with a higher carbonate content exhibited a higher number of mature osteoclasts and approximately a 1.5-fold increase in the resorbed area by osteoclasts. These findings demonstrate that the carbonate content in the CAp coating allows for adjustment of the corrosion rate of biodegradable Mg alloys to suit the affected part of the body. It was also found that once osteoclasts are induced, the CAp coating with a higher carbonate content is resorbed more quickly by the osteoclasts.

In the present work, we have modified glycogen (GLY) with D-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) via the esterification reaction to obtain an amphiphilic polymer (TPGS-GLY). The TPGS-GLY conjugation was confirmed by FTIR and MALDI spectrometry. Furthermore, we prepared polymeric nanomicelles (MCs) encapsulated with palbociclib (PLB) using the solvent casting technique and surface decorated with an antiprogrammed cell death-ligand 1 (PD-L1) antibody to target hypoxic breast tumor. Several physicochemical characterizations have been performed. The MCs were found to be stable under storage, salt ion, and serum stability conditions. In vitro drug release profiles at distinct pH levels (5.5 and 7.4) demonstrate endosomal pH-triggered drug release within cells. The cytotoxicity investigation conducted on MCF-7 and MDA-MB-231 cells showed that the targeted MCs had cytotoxicity 30.94 times and 115.9 times higher than pure PLB, respectively. The cellular uptake, apoptosis, and reactive oxygen species studies have been performed for all of the prepared MCs. Ultrasound and photoacoustic imaging (USG/PAI) in DMBA-induced breast cancer rats revealed that the targeted MCs not only eliminated the tumor but also decreased the hypoxic tumor volume and hindered tumor angiogenesis. The clinical dye indocyanine green (ICG) has been utilized to evaluate the targeting efficiency of MCs toward breast tumors using USG/PAI imaging, demonstrating that targeted micelles has enhanced tumor localization. Furthermore, DiD dye has been employed to investigate organ biodistribution through IVIS imaging.

Multiple sclerosis (MS) is an autoimmune disease of the central nervous system (CNS) that affects approximately 2.8 million people worldwide. In the United States alone, approximately 150 in every 100,000 people will develop MS ( Dilokthornsakul, P., et al. Neurology 2016, 86 (11), 1014-1021). In patients with MS, the myelin sheath, which serves as the insulation for the CNS, is attacked, resulting in the exposure of nerve fibers. The current standard of care for MS is centered around Disease-Modifying Treatments (DMTs) that work to increase the time between MS relapses. FDA-approved DMTs suppress the immune system in a nonspecific manner, putting patients at an increased risk of infections and adverse side effects. Inverse vaccination offers an antigen-specific alternative, aiming to induce immune tolerance to self-antigens without compromising general immune function. This means that the immune system has a reduced or unresponsive response to only the autoimmune antigen and not foreign invaders. This review examines inverse vaccination strategies that employ particle-based delivery systems to promote immune tolerance in MS. It highlights how nano- and microparticles have been engineered to deliver myelin-derived autoantigens, with or without immunomodulatory cues, to induce regulatory T cells, suppress effector responses, or target antigen-presenting cells in a tolerogenic manner. Promising delivery platforms including polylactic-co-glycolic acid (PLGA), acetalated dextran, lignin, iron oxide, gold, and liposomal systems are highlighted, with a focus on how their design influences antigen-specific tolerance induction. Key design principles and challenges are outlined to guide the future development of particle-based inverse vaccines for MS.

The global demand for faster and more effective bone regeneration calls for biomimetic scaffolds that actively guide cell behavior beyond providing structural support. Electrospinning offers unique opportunities to tailor scaffold properties, yet the influence of positive and negative voltage polarities during fabrication on cell-material interactions remains largely unexplored. Here, we investigate poly(l-lactide-co-ε-caprolactone) (PLCL) scaffolds, a statistical copolymer combining strength and elasticity, produced under positive (PLCL+) and negative (PLCL-) polarity. Both scaffold types display comparable morphologies and bulk chemistry. However, X-ray photoelectron spectroscopy reveals charge dependent surface chemistry, with PLCL- enriched in O═C and O-C groups. Zeta potential results highlight pronounced voltage polarity effects under aqueous conditions at pH 7.5, showing -29.19 mV for PLCL+ and -34.77 mV for PLCL-. Biologically, both scaffolds support rapid osteoblast attachment, with robust filopodia and collagen type I deposition by day 14. Strikingly, PLCL+ scaffolds promote deeper cellular infiltration and broader cytoskeletal distribution, whereas PLCL- scaffolds enhance proliferation, but with a flatter cell morphology. These findings reveal that subtle, charge-driven surface chemical differences in random copolymer scaffolds profoundly modulate osteoblast behavior. This work identifies electrospinning voltage polarity as a powerful yet underutilized design parameter for engineering next-generation scaffolds for bone tissue regeneration.

Corneal transplantation is the gold-standard treatment for end-stage corneal disease. However, its clinical use is limited by the global shortage of donor tissue, risks of immune rejection, and postoperative complications. Corneal tissue engineering (CTE) has emerged as a promising alternative strategy, focusing on the development of biocompatible scaffolds that support cellular regeneration while maintaining the critical optical clarity and biomechanical properties of the native cornea. Starch (ST), a naturally derived and abundant polysaccharide, has garnered significant interest as a biomaterial for this application due to its inherent biocompatibility, tunable biodegradability, and amenability to chemical modification. Its physicochemical properties, including controllable hydration, intrinsic optical transparency, and modifiable mechanical strength, are highly conducive to corneal scaffold design. ST can be processed via various techniques such as hydrogel formation, electrospinning, and three-dimensional (3D) bioprinting, to generate structures tailored for specific corneal repair applications. Recent advances focus on functionalizing ST-based scaffolds with bioactive molecules to enhance cellular adhesion and proliferation, improve biomechanical performance, and better recapitulate the native corneal extracellular matrix (ECM). Moreover, ST offers considerable economic and environmental advantages over synthetic polymers due to its cost-effectiveness and sustainable sourcing. Notwithstanding its potential, key challenges persist in optimizing its long-term mechanical stability, controlling its degradation profile to match tissue ingrowth, and ensuring seamless biointegration with host corneal cells. This review provides a comprehensive analysis of the fabrication methodologies, structure-property relationships, and in vitro and in vivo performance of ST-based biomaterials in the context of CTE. Given its versatility and favorable characteristics, ST represents a highly promising substrate for advancing next-generation corneal regenerative therapies.

Fibrosis is driven in part by the transition of healthy fibroblasts to a contractile phenotype called myofibroblasts. The mechanics of the extracellular matrix play a crucial role in regulating cell fates and behaviors during this transition. However, most studies to date focus on cells grown on 2D surfaces and matrices with homogeneous properties. This leaves open how local rigidity differentially regulates the behaviors of both phenotypes in 3D environments, including polarization, contraction, and maintenance of phenotypes, during remodeling. Here, we engineer 3D microgel-in-collagen composites by embedding low-volume fractions of cell-scale microgels with two levels of rigidity, mimicking healthy and pathological tissues that are stiffer than the surrounding collagen but do not significantly change the bulk modulus. We find that microgels serve as mechanical centers: both phenotypes polarize toward microgel inclusions. The polarization response decays as a power-law with distance ∼r^-n, decreasing more slowly for myofibroblasts (n ≈ 0.35) than fibroblasts (n ≈ 0.81), indicating that myofibroblasts are more sensitive to small mechanical variations. In situ measurements finds that forces are highest for myofibroblasts near stiff microgels and lowest for fibroblasts near soft microgels. Local rigidity also stabilizes the myofibroblast phenotype: Both the ordering of the proinflammatory marker α-smooth muscle actin and nuclear Yes-associated protein localization persist for cells cultured with stiff microgels over several days but diminish quickly for those cultured with soft microgels and in pure collagen. Together, these results reveal a rigidity- and phenotype-dependent feedback loop: stiff inclusions induce cell polarization and collagen remodeling via a contractile force, which in turn maintain the myofibroblast phenotype. Our study positions mechanical heterogeneity as a useful and sensitive handle to probe and potentially modulate early fibrotic progressions.