ACS Biomaterials Science & Engineering最新文献

Incision dressings play a crucial role in postoperative care, while hydrogel, as a commonly used polymeric material, can effectively maintain wound moisture and promote wound healing. The present study aims to fabricate a dual-functional hydrogel dressing, carboxymethyl chitosan hydrogel loaded with the nonsteroidal anti-inflammatory drug flurbiprofen (hCMPG-FP), for alleviating postoperative acute pain and promoting incision healing. hCMPG-FP exhibits excellent properties such as gelation, drug release, and degradation, and, in particular, possesses good incision conformability after secondary lyophilization. In vitro and in vivo experiments have confirmed that hCMPG-FP can exert dual functions of wound healing promotion and analgesia, which is associated with the antibacterial activity, coagulation-promoting effect, and cell migration-promoting ability of carboxymethyl chitosan hydrogel, as well as the analgesic and anti-inflammatory properties of flurbiprofen. In conclusion, when acting on incisions, hCMPG-FP regulates multiple pathways such as wound healing and inflammation modulation, exerts ideal dressing functions, and provides a theoretical basis and experimental evidence for the further development of innovative wound treatment strategies.

The pace of progress in tissue engineering and biomedical research could be accelerated by developing improved biofabrication methods that are capable of precisely assembling cells into complex structures. Embedded 3D bioprinting, which often uses packed microgel particles as a support environment, is a promising way to manufacture and culture tissue constructs. The facile reconfigurability of noncohesive microgel support materials enables precise printing but possesses limited mechanical stability. By contrast, cohesive microgels provide enhanced stability yet create kinetic or energetic constraints to reconfiguration during embedded 3D printing processes. Here, we introduce a microgel system that combines the benefits of both cohesive and noncohesive microgels by grafting a poly(N-isopropylacrylamide) (PNIPAM) shell onto polyethylene glycol (PEG) microgel core. These PNIPAM-coated PEG microgels exhibit temperature-dependent interparticle interactions. At room temperature, the microgels remain noncohesive, minimizing constraints on particle reconfiguration and enabling high-quality biofabrication. Upon incubation at 37 °C, the microgels transition to a cohesive state, providing additional structural integrity during tissue culture. We find a phase partitioning behavior between PNIPAM polymer chains and bare PEG microgels that underpins the surface grafting process and correlates with a unique transition in its yielding behavior that is not exhibited by bare PEG microgels. Additionally, the PEG/PNIPAM microgels exhibit only weakly varying linear material properties across temperature shifts, in contrast to pure PEG microgels, which soften dramatically at higher temperatures. Tests of 3D bioprinting structures made from MDCK and 3t3 cells demonstrate the PNIPAM-coated PEG microgel system's ability to maintain cell viability and structure during tissue culture. The work reported here highlights the potential of this thermally tunable microgel system for use in advanced tissue engineering applications, offering precision during fabrication and stability during tissue culture.

Macrophages exhibit phenotypic plasticity that is strongly influenced by their surrounding microenvironment, including extracellular matrix (ECM) components. Hyaluronic acid (HA), a major glycosaminoglycan in ECM, has immunomodulatory effects that are highly dependent on its molecular weight (MW). However, most previous studies have been limited to two-dimensional (2D) culture systems, which were unable to accurately replicate the in vivo environment. In this study, we utilized a three-dimensional (3D) culture system based on HA-based hydrogels to better understand the MW-dependent immunomodulatory effects of HA on macrophages under more physiologically relevant conditions. Three different MWs of HA were chemically modified and cross-linked with PEG-SH₄ to form hydrogels with distinct biophysical properties. Immortalized macrophages were encapsulated within these hydrogels and assessed for the expression of both pro-inflammatory and anti-inflammatory markers. Notably, hydrogels with high-MW HA significantly upregulated the expression of anti-inflammatory markers, indicating that the immunomodulatory effects of HA in 3D culture are affected by its biophysical characteristics. Our findings demonstrate the potential of HA-based hydrogels as customizable ECM-mimetic scaffolds for modulating immune responses in regenerative medicine applications.

Neutrophils, the most abundant immune cells in humans, can promote the progression of many solid tumors. Neutrophils in solid tumor tissues can contribute to immunosuppression and resistance to immunotherapy partially by inhibiting the antitumor activity of natural killer (NK) cells, a group of innate immune cells known as the first line of defense against cancer. Studies in mice show that neutrophils are functionally plastic and can be polarized by molecular cues to show either an antitumor "N1" or a pro-tumor "N2" phenotype. However, the crosstalk between neutrophils and NK cells in human cancer is not well characterized, especially as to how different subtypes of neutrophils could influence NK cell behaviors differently. In this study, we engineered a human cell-based microphysiological system to quantify the distinct effects of antitumor N1-like and pro-tumor N2-like neutrophil subtypes on NK cell behaviors including migration and tumor cytotoxicity. We found that NK cells showed preferential migration toward N1-like neutrophils over N2-like neutrophils, although they showed lower motility in terms of speed, displacement, and directionality after migration toward N1-like neutrophils in comparison to N2-like neutrophils. Moreover, N1-like neutrophils restored the NK cell cytotoxicity against pancreatic tumor spheroids, while N2-like neutrophils suppressed it, although both neutrophil subtypes inhibited NK cell infiltration into tumor spheroids. Our study reveals the dual role of human neutrophils in modulating NK cell behaviors and sheds new light on the nuanced crosstalk between different immune cell types, suggesting the reprogramming of neutrophils to enhance the antitumor functions of NK cells as a potential immunotherapy strategy for cancer.

Scaffolds with neuronal bioactivity are important to promote repair of the central and peripheral nervous systems, in vitro neuronal differentiation and maturation for transplantation, and the integration of electronic devices with neural tissues, among others. Previous work in this area includes the incorporation of growth factors, stem cells, or conducting polymers into scaffolds, but efficacy has been limited. We report here on an extrusion-printable bioactive scaffold that incorporates laminin-mimetic peptide amphiphile (PA) supramolecular filaments, a conducting polymer, and the anionic polysaccharide known as gellan gum. The conducting polymer used was poly(3,4-ethylenedioxythiophene) (PEDOT) with dual functionalization by design with alkoxysulfonates and hydroxyl groups. Hydroxyl groups hydrogen bonded with the polysaccharide, which enhanced both the conductivity and biocompatibility of the scaffolds by preventing the PEDOT from leaching out into cell media. When combined with PA filaments, the scaffold synergistically enhanced neuronal maturation and electrophysiological function in cultures of mouse and human cells. Interestingly, the conducting polymer was found to scavenge reactive oxygen species (ROS) and increase neuronal maturation potentially through cAMP response element-binding protein (CREB) pathways. Furthermore, extrusion printing the scaffold resulted in alignment of the bioactive supramolecular filaments and the cultured neurons, a key feature of natural neural tissues. Our findings suggest this biomaterial scaffold shows potential to promote neural bioactivity in a wide variety of regenerative medicine and bioelectronic applications.

Closed modeling methods for lateral ankle sprain (ALAS) avoid surgical drawbacks but lack standardization due to reliance on the operator's subjective force, leading to variable outcomes. This study aimed to refine a closed ALAS rat model by quantifying manipulation parameters and establishing optimal ranges for different injury grades. Ninety rats were randomly assigned to groups receiving manual ankle inversion under different combinations of force (0-8 N or 8-16 N) and plantar flexion angle (100°-130° or 130°-160°), with control groups. A flexible thin-film pressure sensor and a goniometer were used to standardize the applied force and angle. Multimodal assessments were conducted, including ankle thickness and calcaneofibular ligament (CFL) length measurement, micro-CT, MRI, histopathology (HE and Masson's staining), pain threshold testing, and CatWalk gait analysis at multiple time points up to 28 days postmodeling. The severity of the injury was directly correlated with the applied force and angle. Group D (8-16 N, 130°-160°) exhibited the most severe damage, including avulsion fractures, significant CFL elongation and partial tearing, diffuse MRI signal alterations, and prolonged pain and gait instability (>28 days). Groups A and B (0-8 N, both angles) induced mild injuries (slight edema, minor fiber loosening) with rapid functional recovery by day 7. Group C (8-16 N, 100°-130°) resulted in moderate, partial-thickness ligament injuries with recovery by day 10. Behavioral and imaging findings consistently demonstrated a dose-dependent response to the modeling parameters. This study successfully established a modified and quantifiable closed ALAS rat model. The optimal parameters for a grade I ALAS model are 0-8 N of force with plantar flexion of 100°-130° or 130°-160°. For a grade II ALAS model, the parameters are 8-15 N of force with plantar flexion of 100°-130°. This standardized model enhances reproducibility and provides a reliable foundation for future research into ALAS mechanisms and therapies.

This review systematically summarizes recent advances in multistimuli-responsive smart hydrogels, with a focus on their response mechanisms, synthesis strategies, and broad applications in the biomedical field. Based on a hydrophilic three-dimensional cross-linked network structure, smart hydrogels can sensitively respond to external stimuli such as temperature, pH, light, electricity, magnetic fields, and enzymes, enabling functions such as structural transformation, controlled drug release, and tissue repair. The article elaborates on various synthesis strategies, including chemical and physical cross-linking, microfluidics and 3D printing, double-network and nanocomposite structures, DNA-based biohydrogels, and self-healing hydrogels. It also analyzes specific response mechanisms─electrical, thermal, photoresponsive, magnetic, pH, and enzymatic─along with their application cases in drug delivery, wound healing, neural repair, and tumor therapy. Although challenges remain in functional integration and clinical translation, such as mechanical performance, biosafety, and scalable production, future developments involving multiresponse synergy, personalized design, and intelligent regulation are expected to promote their applications in precision medicine and flexible electronics.

Skeletal muscle is an important organ system of the human body, which is responsible for maintaining body posture and movement and also plays an essential role in metabolic and endocrine functions. Although skeletal muscle has intrinsic regeneration ability, loss exceeding approximately 20% of the mass or volume of an individual muscle is considered volumetric muscle loss (VML), which requires surgical intervention for repair. Tissue engineered scaffolds prepared using techniques such as electrospinning, hydrogel casting, particulate leaching, freeze-drying, freeze-thawing, and bioprinting are promising for treating VML injuries. In this review, we discuss various extrusion-based bioprinting strategies to fabricate skeletal muscle constructs aimed at treating VML. Further, this review provides a comprehensive overview of various extrusion-based bioprinting techniques to fabricate muscle tissues such as support-based, co-axial, in situ, cryobioprinting, spheroids, and 4D bioprinting. Different bioink systems, their key properties, and similarities with the native extracellular matrix (ECM) are elaborated. In addition, commonly used preclinical models for assessing the efficacy of skeletal muscle constructs, as well as various experimental methods for assessing functional recovery after VML injuries treated with engineered tissue constructs, are discussed. The limitations of current approaches in the successful fabrication of skeletal muscle constructs using bioprinting techniques are highlighted. Finally, the future scope in the development of more efficient experimental tools to assess the in vivo efficacy of bioprinted constructs to treat VML are discussed.

Degenerative eye diseases are major causes of irreversible vision loss worldwide, but effective treatments remain limited, partly due to the lack of effective human models. Retinal organoids derived from stem cells can recapitulate key structural and physiological features of the human retina, offering powerful tools to study disease mechanisms and develop new therapies. Here, we review recent progress in engineering retinal organoids and eye-on-a-chip models for modeling degenerative eye diseases, with a focus on engineering innovations. We first describe conventional methods for organoid differentiation and characterization along with current outstanding challenges. To better engineer retinal organoids, new strategies that leverage microfluidics and biomaterials have emerged to regulate dynamic and physiologically relevant environments for organoid differentiation. Moreover, the integration of artificial intelligence, multimodal sensing, and data analytics improves the monitoring and prediction of retinal function and therapeutic outcomes. Finally, we discuss future directions in innovating next-generation retinal organoid and eye-on-a-chip models for disease modeling, drug discovery, and vision restoration, highlighting their potential for precision ophthalmology.