ACS Biomaterials Science & Engineering最新文献

Spinal cord injury (SCI) leads to irreversible sensory and motor deficits due to its limited capacity for regeneration of the central nervous system (CNS). While the current clinical strategies focus on neuroprotection and stabilization of the symptoms, they offer very little in terms of restoring long-term functional recovery. Three-dimensional (3D) bioprinting has opened new possibilities for constructing patient specific scaffolds that mimic the structural and biochemical complexities of native spinal tissue. The incorporation of cells, biomaterials, and growth factors, in 3D bioprinting provides incomparable control over the architecture of the scaffold, which in turn enables recreation of biomimetic environment that supports axonal outgrowth and neural recovery following SCI. This review focuses on the recent advances in 3D bioprinting techniques for SCI repair and discusses the potential of the techniques to be implemented in SCI models. Focus is placed on the bioink formulation, scaffold design strategies, and emerging functional features. The amalgamation of current findings underscores the potential of 3D bioprinting as a mature platform for the development of next-generation therapies for spinal cord injury.

Extracellular matrix (ECM) hydrogels are recognized as promising biomaterials for regenerative medicine owing to their ability to recapitulate the native tissue microenvironment. The human amniotic membrane (AM), readily available and posing little to no ethical concerns, is rich in ECM components with inherent wound-healing potential. This study aimed to develop and characterize thermosensitive hydrogels derived from a decellularized AM and assess their therapeutic potential for diabetic wound healing. The native AM was subjected to detergent-enzymatic decellularization to remove the cellular content while preserving the essential ECM. The resulting acellular AM was lyophilized, cryomilled, and digested with pepsin under acidic conditions at three different concentrations. The pregel solutions were neutralized and thermally induced to form AM ECM hydrogels at 37 °C. The physicochemical properties, including gelation kinetics, swelling, porosity, mechanical stiffness, and biodegradation, were evaluated. The biological evaluation was assessed using fibroblasts, keratinocytes, and endothelial cells through live/dead staining, the MTS assay, and analyses of ROS production, apoptosis, cytoskeletal organization, and cell migration. Proteomic profiling was conducted to identify the retained matrisome proteins. The in vivo performance was tested in a diabetic murine full-thickness wound model. AM ECM hydrogels exhibited temperature-dependent gelation (t_1/2: ∼12.75-27 min), high water content (>97%), and >60% porosity. All formulations supported >70% cell viability at 24 h and >300% proliferation at 72 h, with negligible ROS production, minimal apoptosis, and preserved cytoskeletal integrity. The proteomic analysis confirmed the maintenance of matrisome proteins related to epithelial differentiation, angiogenesis, and tissue repair. The in vivo study demonstrated that the AM ECM hydrogel accelerated wound healing, evidenced by early wound closure, along with vascular stabilization, regulated inflammatory response, and ECM stabilization compared to those of the control group. These findings collectively demonstrate that AM ECM hydrogel treatment in diabetic mice ameliorates wound pathology, as evidenced by reduced severity, a modulated inflammatory response, and decreased fibrotic burden.

Treatment of complex bone defects requires scaffolds that readily conformably fit to the contours of irregular defects while also providing the requisite mechanical properties, tailorable resorbability, and bioactivity. In this study, we investigated the osteogenic capacity of a family of shape memory polymer (SMP) composite scaffolds prepared as networks from acrylate-derivatized star- or linear-poly(ε-caprolactone) (PCL) or as semi-interpenetrating networks (semi-IPNs) with the inclusion of star- or linear-poly-l-lactic acid (PLLA). These networks were fabricated as porous composite scaffolds with up to 10 wt % 45S5 Bioglass (BG) localized to the pore walls using a solvent-casting particulate leaching process. In noncomposite scaffolds (i.e., 0 wt % BG), PCL/PLLA semi-IPNs demonstrated mixed effects on human bone marrow stem cell production of osteogenic proteins, depending on the linear or star architecture of the PCL and PLLA. Composite scaffolds with 10 wt % BG generally showed reduced levels of early osteogenic proteins, such as COL1A1, with the 10 wt % BG PCL/PLLA semi-IPNs also displaying marked increases in late-term osteogenic proteins, such as osteocalcin. These results suggest a potential trade-off between the beneficial effects of BG in terms of stimulating late-term osteogenesis and associated reductions in the deposition of the critical bone structural component COL1A1. Assessment of composite scaffolds with intermediate 5 wt % BG maintained the higher COL1A1 levels of 0 wt % BG scaffolds, while stimulating late-term ECM deposition and mineralization approaching those of the 10 wt % BG scaffolds.

Parkinson's Disease (PD) is a progressive neurodegenerative disorder characterized by dopaminergic neuronal loss, oxidative stress, and mitochondrial dysfunction. Current treatment strategies are largely symptomatic and fail to halt disease progression. This research work explores a novel dual-modal therapeutic strategy combining Photobiomodulation (PBM) using near-infrared (NIR) light with nanotechnology-enhanced delivery of Rosmarinic Acid (RA) for the treatment of PD. Building upon the findings of previous works, which established the neuroprotective potential of RA, this study extends its application to PD treatment through the development of RA-loaded liposomes (RA@LP) and their integration with NIR-induced PBM. As a noninvasive modality, NIR light has demonstrated efficacy in stimulating mitochondrial activity, promoting ATP production, and reducing oxidative stress through PBM mechanisms. In parallel, RA, a potent natural antioxidant, has been encapsulated within liposomal nanocarriers to enhance its stability, bioavailability, and targeted delivery to affected neuronal tissues. The combined therapeutic platform of PBM and RA@LP is designed to eliminate endogenous and exogenous reactive oxygen species (ROS), thereby breaking the self-perpetuating cycle of oxidative stress and mitochondrial damage underlying PD pathogenesis. We highlight in vitro investigations that demonstrate the synergistic effects of PBM and RA@LP on neuronal cells. The results indicate that this dual approach protects mitochondrial integrity and improves cellular viability under PD-like oxidative conditions. By broadening the scope to include in vitro analysis, the study provides deeper mechanistic insights into the cellular responses to light-based and nanomedicine therapies. This work presents a promising, noninvasive, and multitargeted strategy for PD treatment, with potential implications for translational research. Integrating phototherapy and nanotechnology represents a significant advancement in developing effective neuroprotective interventions.

Lactate, the main product of the Warburg effect, exerts both intrinsic effects on cancer cell metabolism and noncell autonomous effects that promote tumor development, metastasis, and treatment resistance. As such, glycolytic dependence in tumors is frequently associated with poor clinical outcomes. Targeting lactate metabolism has emerged as a promising strategy to enhance the efficacy of conventional therapies. Here, we investigate the therapeutic potential of targeting lactate metabolism via inhibiting MCT1, MCT4, and MPC in PC3 and FaDu tumor cell models. We confirmed lactate as a substrate that fuels mitochondrial respiration and supports cell survival under hypoxic conditions. Inhibition of lactate influx mediated by 7ACC2 reduced oxygen consumption, sensitizing tumor cells to radiation in both 2D-cell cultures and 3D-spheroid models. Encapsulation of 7ACC2 in DPPC liposomes using microfluidics preserved radiosensitizing activity in both systems, promoting reoxygenation, while overcoming the pharmacological limitations of the free drug. This liposomal formulation therefore represents a promising therapeutic approach to help mitigate hypoxia-induced radioresistance.

This study aimed to reconstruct the hypothalamic-pituitary axis using an organ-on-a-chip (OOC) model and to evaluate the modulatory role of phoenixin-20 (PNX) in the regulation of the gonadotrophic axis in sheep. Sixteen female Polish Merino lambs were used as tissue donors to create microfluidic chips containing paired hypothalamic and pituitary slices connected via perfused channels. This system enabled continuous medium flow and maintenance of functional neuroendocrine interactions under ex vivo conditions. The OOC platform was used to analyze changes in the expression of gonadotropin-releasing hormone (GnRH), kisspeptin (Kiss), neurokinin B (NKB), and prodynorphin (pDYN) in the hypothalamus, as well as luteinizing hormone (LH) and follicle-stimulating hormone (FSH) expression and secretion in the pituitary. PNX treatment significantly increased hypothalamic GnRH expression, while the blockade of neuropeptide Y receptors (NPY1R and NPY5R) diminished this response, suggesting that PNX effects are at least partially mediated through NPY-dependent pathways. Moreover, PNX altered the transcription of Kiss, NKB, and pDYN, key components of the GnRH pulse generator, and modulated LHβ mRNA expression in the pituitary. Changes in the LH and FSH concentrations further supported a receptor-specific mechanism of PNX action. The developed hypothalamo-pituitary OOC model proved valuable for studying neuroendocrine control of reproduction. This system offers a physiologically relevant and ethically sustainable alternative to in vivo experiments, enabling precise investigations of molecular and hormonal mechanisms within the gonadotrophic axis.

Bacterial infection, excessive inflammation, and oxidative stress pose significant challenges to the wound healing process. Multifunctional hydrogels, as wound dressings, hold promising potential to overcome the current obstacles in wound treatment. In this study, three metal ions (copper, zinc, and calcium, CZC) were mixed with sodium alginate (SA) to form a slowly cross-linked network, followed by the incorporation of glycyrrhizic acid (GA) to establish a CZC-SA-GA dual-network hydrogel. Copper ions exhibit antibacterial and angiogenic properties. Zinc ions synergistically enhance antibacterial efficacy and provide antioxidant effects. Calcium ions promote structural cross-linking and facilitate cell migration. The introduction of GA significantly enhances the mechanical strength of the hydrogel (compressive modulus increased by approximately 67%) and endows it with anti-inflammatory activity. The CZC-SA-GA hydrogel demonstrates excellent cytocompatibility, promotes cell migration and angiogenesis (VEGF is significantly upregulated), and exhibits potent anti-inflammatory (reduces the expression levels of NO, IL-6, and iNOS) and antioxidant effects (reduces MDA activity and ROS accumulation and increases T-GSH level). Additionally, it shows broad-spectrum antibacterial activity against both Gram-positive and Gram-negative bacteria (bactericidal efficacy ≈100%). In a murine full-thickness skin wound model, the application of the CZC-SA-GA hydrogel accelerated wound healing (wound closure accelerated by ∼20%). The development of natural drug-based hydrogels with integrated antibacterial, anti-inflammatory, and antioxidant properties presents a promising strategy for treating severe skin wounds.

Hydrophilic macromolecules with versatile bioactivities have potential in regenerative medicine and cosmetics but are limited by their inferior transdermal capacity. Here, inspired by the transdermal capacity of silk nanofibers (SNF), recombinant collagen XVII (RCL), a model of hydrophilic macromolecules, was assembled with SNFs to form nanocomplexes. The nanostructures and sizes of the complexes could be controlled through changing the ratio of SNF and RCL, which then resulted in various transdermal capacities. Although RCL retained nonpermeable behaviors, the nanocomplexes with optimal ratios of SNF and RCL showed a desirable transdermal capacity and skin barrier-repairing capacity. Better bioactivity was also achieved for the SNF-RCL nanocomplexes, suggesting desirable synergistic action. In the in vivo study, topical application of the nanocomplex gels promoted tissue healing of the photodamaged skin, superior to that treated with pure RCL and SNF. It is suggested that the SNFs could form transdermal nanocomplexes with hydrophilic macromolecules without the compromise of bioactivities, implying the potential of developing SNF-hydrophilic macromolecules' transdermal delivery systems for skin disease.

Uncontrolled hemorrhage and delayed wound healing represent critical challenges in clinical practice. To address these issues, we developed a bioinspired honeysuckle-loaded mesoporous silica nanoparticle (HS-MSN) system that integrates sustained drug release with rapid hemostasis and pro-healing functions. Inspired by the unique surface structure of waxberries, HS-MSN was synthesized via a facile adsorption method, exhibiting high surface area, hierarchical porosity, and efficient loading of bioactive honeysuckle extract. The nanocomposite demonstrated a sustained release profile lasting up to 72 h, significantly enhancing the durability and bioavailability of therapeutic components. In vitro studies showed that HS-MSN accelerated clotting initiation within 10 s in both normal and hemophilic blood models, outperforming its individual components (bare MSN or honeysuckle extract alone). The material also exhibited excellent biocompatibility, hemocompatibility, and efficient cellular uptake. Moreover, the sustained release of honeysuckle constituents potently scavenged reactive oxygen species and suppressed pyroptosis by inhibiting NLRP3 inflammasome activation and pro-inflammatory cytokine release. In multiple murine injury models (tail amputation, liver wound, and limb amputation), HS-MSN achieved rapid hemostasis, significantly reduced blood loss, and shortened clotting time. Most notably, in a hemorrhagic full-thickness wound model, HS-MSN treatment resulted in substantially accelerated wound closure, with (67.02 ± 2.56)% healing achieved within 7 days, enhanced collagen deposition, and improved re-epithelialization, significantly outperforming control groups. The combination of sustained release capability, rapid hemostasis, and potent healing promotion makes HS-MSN a promising multifunctional nanotherapeutic for managing acute hemorrhagic wounds and facilitating tissue regeneration in emergency and surgical settings.

The development of poly(lactic-co-glycolic acid) (PLGA)-based microsphere scaffolds with comprehensive osteogenic activity, hydrophilicity, mechanical strength, and biocompatibility remains a significant challenge. Here, we constructed a hexagonal mesoporous silica (HMS)/PLGA composite microsphere scaffold (HP). Subsequently, we further developed a polydopamine (PDA)-modified version of HP (PHP) by applying a PDA coating to its surface. Compared with HP, PHP exhibited improved compressive strength and hydrophilicity while maintaining desirable porosity. In vitro, PHP promoted BMSCs proliferation and osteogenic differentiation, upregulated osteogenic gene expression, and induced macrophage polarization toward the M2 anti-inflammatory phenotype. In a rat calvarial defect model, PHP significantly enhanced bone regeneration, as confirmed by micro-CT and histological analyses, and maintained elevated expression of BMP-2 and VEGF to support osteogenesis and angiogenesis. Immunostaining further demonstrated increased CD163 and decreased iNOS expression, indicating an immunomodulatory effect. All materials showed favorable biocompatibility. This work integrated the surface functionalization of PDA with the structural features of HMS, demonstrating that the ternary composite scaffold achieved simultaneous regulation of the immune microenvironment and osteogenesis, providing a promising strategy for clinically translatable bone repair materials.