ACS Biomaterials Science & Engineering最新文献

Wound healing and tissue reconstruction following a skin defect, particularly the restoration of full skin function and appearance, remain a major clinical challenge. Traditional hydrogel dressings face limitations in mechanical strength, poor permeability, and a lack of multifunctionality, making them inadequate for meeting the dynamic demands of the wound healing process. Fibrous hydrogels offer a compelling alternative by combining the high-water content and biocompatibility of hydrogels with the anisotropic structure and design flexibility of fibers, allowing them to closely mimic native tissue architecture. In this review, we introduce a three-tier framework based on structural, functional, and responsive programmability to systematically classify and evaluate programmable hydrogel fibers for wound healing. Recent advances in structural design strategies, functionalization approaches, and biomedical applications are summarized. Notably, this review uniquely integrates structural design, functional strategies, and translational potential within a unified programmability framework, while critically examining current limitations and challenges in clinical translation. Despite these obstacles, hydrogel fibers hold considerable promise for personalized tissue engineering and functional regeneration.

In recent years, with the rapid advancement of tissue engineering and regenerative medicine, cell-laden 3D bioprinting has emerged as a key driving force in the construction of functional artificial skin grafts. By precisely controlling the three-dimensional spatial distribution of cells, biomaterials, and growth factors, this technology can replicate the complex hierarchical structure and physiological functions of native skin. This review aims to provide a comprehensive overview of the key research advances recently achieved in the field of cell-laden 3D bioprinting of artificial skin. In this review, we summarize the physiological architecture of native skin, the selection and enhancement of common bioinks, strategies to improve cellular responses during printing, analysis of 3D bioprinting technologies and fabrication approaches, and the opportunities and challenges of clinical translation, aiming to provide optimized insights for the preparation of cell-laden 3D bioprinted artificial skin grafts. It systematically examines the biomimetic structural principles of engineered skin, innovative bioink formulations and their cytocompatibility, the evolution of 3D bioprinting technologies and improvements in resolution, breakthroughs in skin tissue functionalization including vascularization, innervation, appendage and pigmentation regeneration, the opportunities and challenges facing clinical translation and future perspectives.

Objective: This review evaluates nanozymes as catalytic biomaterials for upper respiratory tract infection (URTI)-related diagnosis, therapy, and prevention, with particular attention to differences in the maturity of evidence across these applications. The anatomically adjacent middle ear is also considered as a relevant model of biofilm-associated infection and barrier-limited local delivery. Methods: We reviewed studies involving respiratory pathogens, sinonasal disease, pharyngitis, intranasal vaccination, and otitis media. Evidence from other disease models was included only when it addressed a specific materials problem relevant to the upper airway, such as catalytic regulation, biofilm disruption, mucus transport, or local retention. Results: Diagnostic applications currently have the strongest evidence base, particularly for catalytic signal amplification in respiratory pathogen assays. In contrast, therapeutic evidence remains sparse and predominantly preclinical, with direct treatment studies in URTIs especially limited. Preventive applications are less extensively studied and are represented mainly by proof-of-concept intranasal influenza vaccination. Across these applications, performance depends on catalytic activity in protein- and mucus-rich media, biofilm penetration, control of pro-oxidant and antioxidant effects, and delivery to the intended anatomical site. Evidence from other anatomical sites provides useful design principles but should not be interpreted as evidence of efficacy in URTIs. Conclusion: Nanozymes should currently be regarded as engineerable catalytic biomaterials rather than clinically established anti-infective platforms for URTIs. Translation will require reproducible activity in airway-relevant environments, effective site-specific delivery, appropriate safety margins, and validation in disease-relevant models.

Metastasis and postoperative recurrence of malignant tumors remain critical obstacles that undermine clinical therapeutic efficacy. Traditional chemodynamic therapy (CDT) is plagued by three inherent, hard-to-resolve drawbacks: abundant intratumoral glutathione (GSH) quenches reactive oxygen species; robust systemic antitumor immunity fails to be activated; and unbound iron catalysts initiate off-target Fenton cascades within healthy tissues, inducing systemic oxidative injury and toxic side effects. To address these critical barriers, we rationally designed a bifunctional ferrocene-cystamine conjugate (FD) and encapsulated this payload within amphiphilic hyaluronic acid-cinnamaldehyde (HA-CA) Schiff-base nanomicelles, thereby fabricating a nanoplatform designed to target HA receptors (presumably CD44) with sequential pH/GSH responsiveness. The resultant HA-CA@FD nanomicelles attain a high FD loading efficiency of 36 ± 2% and display excellent colloidal stability under physiological environments. Once exposed to the acidic, reductive tumor microenvironment, the nanocarrier undergoes structural dissociation to liberate loaded FD. The released FD depletes intracellular GSH through two cooperative redox routes-disulfide bond cleavage and reversible Fe2+/Fe3+ cycling-while simultaneously generating massive cytotoxic hydroxyl radicals (·OH) to elicit potent immunogenic cell death. In vitro biological characterizations validate that the nanomedicine raises the proportion of mature dendritic cells to 66.7% and elevates the percentage of anti-tumor M1-type macrophages from 3.9 to 48.2%. In vivo assays using bilateral 4T1 tumor-bearing mice reveal that intratumoral injection of HA-CA@FD diminishes primary tumor weight by 67% and abscopal contralateral tumor weight by 52%. This therapeutic regimen substantially augments intratumoral infiltration of CD4+/CD8+ effector T cells and diminishes immunosuppressive regulatory T cell (Treg) populations, accompanied by elevated memory T-cell signatures that suggest potential for establishing durable antitumor immune responses. This modular, biocompatible biopolymer nanosystem surmounts the core limitations of classic CDT agents, furnishing a straightforward, translation-ready nanoengineering paradigm for precision combinatorial chemo-dynamic-immunotherapy against solid tumors.

Silk cocoons consist primarily of fibroin and sericin but also contain hundreds of uncharacterized proteins with unknown biological function. This study characterizes a silk extract produced using a recently developed extraction method that preserves native protein structure and composition, revealing proteins that are likely lost or overlooked using conventional extraction approaches. As expected, it extracted the primary fibroin and sericin proteins, but unexpectedly, the extract was dominated by sericin 3 and an 18.4 kDa protein with unknown function. We propose two possible functions: firstly, that it facilitates sericin 3 expression or secretion and secondly, that it acts as a "calcium chelator", acting as a molecular trigger for fiber formation. In addition, analysis of the theoretical fractional charges of the primary silk proteins predicts that sericin 3 and fibrohexamerin (P25) transitions from negatively charged to neutral charge at the pH in the anterior silk gland, suggesting a previously unrecognized mechanism for regulating protein interactions during spinning. Together, these findings point towards an explanation for how silkworms can store silk proteins at high concentrations in the gland without aggregation then selectively destabilize the mixture on demand during fiber spinning. This understanding could have significant implications for the development of regenerated silk feedstocks for artificial silk spinning.

Perfused spheroid platforms enable continuous mass transport, but the role of chamber architecture in in situ spheroid assembly remains insufficiently understood. Here, we developed a perfusable organ-on-a-chip platform for the in situ formation and culture of HepG2 spheroids and compared rectangle-, rhombus-, and round-chamber designs under matched key channel dimensions. Two-dimensional (2D) simulations revealed geometry-associated differences in intragel velocity and shear-rate distributions. Experimentally, chamber design was associated with differences in spheroid morphology, qualified spheroid proportion, and viability, with the round chamber showing the best overall performance under standardized conditions. Rho-associated coiled-coil-containing protein kinase (ROCK) inhibition impaired early spheroid compaction without a significant geometry-dependent treatment effect, whereas Matrigel supplementation improved spheroid morphology, hepatic functional readouts, and viability. Under nominal APAP and TBHP exposure conditions, chip and ultra-low-attachment plate cultures exhibited distinct concentration- and time-dependent injury responses. Together, these findings identify chamber architecture and extracellular matrix (ECM) composition as important design variables in perfused spheroid culture and provide a comparative platform for studying liver spheroid development and drug-induced injury under perfusion.

Granular hydrogels composed of jammed microgels have emerged as promising biomaterials for 3D bioprinting due to their tunable viscoelastic properties and ability to incorporate bioactive molecules and encapsulate cells within the interstitial spaces between the particles. Here, we present a new strategy to achieve spatially controlled release of bioactive molecules using κ-carrageenan microgels having a triple role as a printable bioink, a supportive matrix, and a carrier for bioactive molecules. To enable molecule incorporation, we employed a freeze-drying and absorption loading technique and demonstrated that trehalose preserves microgel morphology and rheological properties. Release kinetics of small (fluorescein) and large (BSA) model molecules revealed sustained diffusion-driven release. The microgels retained their printability and flow properties after rehydration and enabled precise printing within a granular support material. As a proof of concept, we directed human adipose-derived mesenchymal stem cell (hADMSC) differentiation into adipocytes by printing microgels loaded with an adipogenic medium at distinct regions within the support material. Differentiation was confirmed via lipid droplet staining and quantitative analysis. A significantly greater lipid accumulation was observed in hADMSC constructs located within defined, spatially patterned ADP-loaded microgels compared with constructs located in the surrounding region. Our findings demonstrate the potential of this platform for engineering complex, multicellular constructs with region-specific biochemical microenvironments through embedded bioprinting.

Overcoming oxidative stress resulting from reactive oxygen species (ROS) overload in the microenvironment of bone injury is crucial for bone repair. This study developed a multifunctional composite scaffold composed of zein, adenosine-calcium phosphate (ACP), and epigallocatechin gallate (EGCG) for enhanced bone regeneration through antioxidant activity. For the preparation of the Zein/ACP/EGCG (Z/A/E) composite scaffold, ACP nanoparticles were first synthesized using an enzymatic reaction and characterized by SEM, EDS, FTIR, and XRD. ACP nanoparticles showed great biocompatibility and osteoinductivity within a certain dose range in vitro. A three-dimensional (3D) porous Zein/ACP (Z/A) composite scaffold was fabricated by compression molding and particulate leaching, followed by the adsorption of EGCG onto its surface. The final Z/A/E composite scaffold exhibited enhanced surface hydrophilicity, which facilitated the adhesion, proliferation, and differentiation of osteoblasts. Mechanistically, the Z/A/E composite scaffold promoted osteogenesis while concurrently inhibiting osteoclastogenesis, primarily through its ROS-scavenging capability. The bidirectional regulation of bone remodeling by the Z/A/E composite scaffold was demonstrated by significant repair of hydrogen peroxide-induced calvarial defects in ex vivo cultured explants from neonatal mice, confirmed by μ-CT and histological evaluation. Collectively, this Z/A/E composite scaffold, which leverages antioxidant activity to rebalance bone homeostasis, represents a promising strategy for bone regeneration.

Bioinspired antifreeze polypeptides can be used as macromolecular cryoprotectants, but the wide application of charged polypeptides remains a challenge for cell cryopreservation due to the possible membrane-destructive activity. In this work, positively charged poly(l-methionine) derivatives tethering threonine-mimetic methyl and hydroxyl groups (PMOH) are synthesized, which can form coacervates with anionic γ-poly(glutamic acid) (PGA) with or without trehalose via liquid-liquid phase separation. The coacervate consisting of PMOH and PGA each at 20 mg/mL with 0.2 M trehalose exhibits a strong ice recrystallization inhibition activity with a mean largest grain size of 22.2 ± 1.9% relative to PBS, attributable to the depressed diffusion of water molecules through the highly confined water and contribution of trehalose. The coacervation of PMOH/PGA could also promote ice nucleation owing to the charged nature of the polymers. Actually, the PMOH/PGA coacervates show acceptable cytocompatibility and cryopreservative effects on cell cryopreservation by reducing half of the dimethyl sulfoxide dosage. This work offers a valuable strategy for the utility of charged polypeptides in cryopreservation.

While polyetheretherketone (PEEK) is often considered the standard non-metal alternative for orthopedic implants, it is also just one member of a larger family of polyaryletherketones (PAEKs) that have not been as thoroughly studied for biomedical applications. This work aims to evaluate the surface properties of two medical-grade PEEKs (Types 1 and 2), two grades of polyetherketoneketone (PEKK A and C), and one low-melt PAEK, and to understand how these results correlate with protein adsorption. The surface free energy (SFE) of additively manufactured PAEK samples was measured using the Owens, Wendt, Rabel, and Kaelble (OWRK) method. Differential scanning calorimetry (DSC) was used to evaluate the thermal properties of these samples, and protein adsorption was quantified after immersion in bovine serum albumin (BSA) and fetal bovine serum (FBS). Despite both being classified as PEEK, Types 1 and 2 exhibited significant differences in water contact angle (89.55° vs 76.15°) and in the polar component of SFE (0.02 vs 1.57 mN/m) (p < 0.05). After 8 h of immersion in BSA, PEKK A had significantly more protein adsorption than all other groups, and in FBS, PEKK A and Type 2 PEEK both had significantly more protein adsorption than Type 1 PEEK (p < 0.05). Using a Pearson analysis, a significant correlation was found between the polar component of SFE and protein adsorption in FBS after 8 h (p < 0.05). This work demonstrates that innate differences in surface properties exist among members of the same PAEK material family, and that these differences can substantially influence protein adsorption.