Alveolar ridge deficiency remains a significant clinical challenge in dental implantology, often necessitating bone augmentation procedures. While autogenous bone grafting is considered the gold standard, its limitations, including donor site complications and limited availability, have prompted the development of alternative bone graft materials. In this study, we fabricated a novel polycaprolactone (PCL)/β-tricalcium phosphate (β-TCP)@zinc oxide (ZnO) composite scaffold via direct ink writing (DIW) three-dimensional (3D) printing. The scaffold integrates a biomimetic porous architecture with a controlled ion-release strategy to enhance osteogenic performance. The characterization of the material confirmed excellent chemical stability, hydrophilicity, and tunable degradation behavior. The incorporation of ZnO facilitated the sustained release of bioactive ions (Ca2+, PO4 3-, and Zn2+), significantly improving the scaffold's bioactivity. In vitro assessments revealed that the scaffold with 2% ZnO (PTZ-2) exhibited optimal cytocompatibility and osteogenic differentiation capacity, promoting alkaline phosphatase activity and mineralized nodule formation in MC3T3-E1 cells. In a rat cranial defect model, the PTZ-2 scaffold achieved approximately 95% new bone area after 12 weeks. Histological analysis further confirmed the presence of continuous, highly mineralized bone matrix with excellent osseointegration capability. These findings collectively indicate that the 3D-printed PCL/β-TCP@ZnO composite scaffold has great potential for clinical translation in bone defect regeneration.
Chronic wound healing is a dynamic and complex physiological process. Bacterial biofilms and antibiotic resistance seriously impede the repair of chronic wounds. Traditional dressings cannot respond to the characteristic acidic microenvironment (pH 4.5-6.5) of infected wounds, making it difficult to achieve targeted antibacterial effects. pH-responsive hydrogels can precisely release antibacterial components through acid triggering. They can specifically recognize the changes in the acidic micro environment created by bacterial metabolites, and then achieve the on-demand release of functional components, showing great potential in chronic wound management. This paper systematically reviews the dynamic cross-linking mechanism of pH-responsive hydrogel dressings, focuses on summarizing their antibacterial strategies, summarizes their functional characteristics in controlling bacterial infections, promoting tissue repair, and implementing wound monitoring, and prospectively discusses their clinical translation potential.
Stem cell-based therapies derived from various sources hold significant potential in regenerative medicine due to their unique properties, particularly their ability to differentiate, self-renew, and modulate the immune system. A polymer-encapsulated Mesenchymal stem cell (MSC) approach can create protective environments for stem cells, enhancing overall therapeutic efficacy. Gelatin Methacrylate (GelMA) is used as a model extracellular matrix to encapsulate MSCs for potential applications in cell-based therapy and bioprinting. This study aims to understand the limitations of GelMA-encapsulation-based cell therapy for an injured tissue. Due to the harsh microenvironment at the implantation site, directly injected stem cells for treatment are affected by factors such as nutrient and oxygen deprivation, immune rejection, reduced cell retention, and inflammatory cytokines. In the current study, we tried to mimic this system. We optimized the GelMA hydrogel cell-encapsulation composition from synthesis through physicochemical characterization, and then tested its cytocompatibility with MSCs. We have further performed numerical modeling to understand and control the behavior of MSCs within the 3D GelMA hydrogel construct under varying metabolic and immunological stress microenvironmental conditions, thereby optimizing the boundary conditions of GelMA-based cell delivery systems.
Lignin's intrinsic fluorescence and bioactivities (antioxidant, antibacterial, photoprotective) arise directly from its polyphenolic macromolecular architecture. This review critically integrates lignin-based fluorescent polymers for intelligent bone regeneration, bridging lignin photophysics and tissue engineering. We dissect the macromolecular origins of lignin's biological modalities and its aggregation-induced emission (AIE) behavior, where clustering of phenylpropanoid units transforms concentration quenching into a luminescent design advantage. Synthetic strategies that employ lignin as macromonomers, initiators, and crosslinkers to fabricate fluorescent polymers with tunable optics and preserved bioactivity are surveyed. We highlight two emerging applications: non-invasive, real-time tracing of scaffold degradation via intrinsic fluorescence, and integrated theranostics that synergize antibacterial defense, oxidative stress modulation, and pro-osteogenic induction within a single macromolecular system. Critically, we identify five translational bottlenecks-heterogeneity-driven photophysical variability, insufficient quantum yield, long-term chromophore biosafety, multifunctionality‑processability trade-offs, and batch‑to‑batch fluorescence inconsistency-and propose chemical and processing strategies to overcome them. By merging lignin macromolecular chemistry, fluorescence photophysics, and bone biology, we position lignin-based fluorescent polymers as a distinct bioactive class where therapeutic function is programmed into the polymer backbone, offering a promising paradigm for macromolecular design.
Atrial fibrillation (AF)-related ischemic stroke carries substantial clinical risks, and transcatheter left atrial appendage closure (LAAC) constitutes a core stroke preventive intervention. Conventional non-degradable occluders are hampered by permanent foreign body retention, insufficient anatomical conformability, and sustained long-term foreign-body inflammatory stimulation. Fully biodegradable materials offer a novel approach for device advancement. This review summarizes the characteristics and composite modification technologies of poly-p-dioxanone (PPDO) and polylactic acid (PLA), analyzes the application advantages and latest research progress of biodegradable closure devices, discusses technical challenges and corresponding solutions, and prospects their development trends toward multi-functionality and intellectualization. Owing to their intrinsic advantages of complete in vivo resorption and tunable mechanical/degradation properties, such composites are poised to emerge as the next-generation mainstream LAAC implants, advancing AF-associated stroke prophylaxis toward precise, biointegrated interventional therapy.
Bone scaffolds represent a common surgical approach for repairing bone defects, and the clinical demand for effective graft substitutes remains high due to the limited availability of autologous bone. Titanium (Ti) and its alloys are widely used as load-bearing implants; however, their inherent biological inertness hinders early osteogenesis and delays osseointegration. With advances in bone tissue engineering, biofunctionalized 3D-printed porous Ti scaffolds have emerged as a promising strategy to overcome these limitations. Among the various biomaterials investigated, silk fibroin (SF) has attracted considerable interest owing to its excellent biocompatibility, controllable biodegradability, tunable mechanical properties, and intrinsic capacity for drug loading. The integration of SF onto Ti scaffolds through coatings, hydrogels, or composite structures mitigates the biological inertness of Ti and confers additional functionalities, such as controlled drug release, osteogenic stimulation, and immunomodulation. This review summarizes the structural characteristics, drug-delivery behavior, and degradation mechanisms of SF, and highlights current evidence on its osteogenic and anti-inflammatory effects both in vitro and in vivo when combined with porous Ti scaffolds. Furthermore, we discuss emerging multifunctional strategies, including composite coatings incorporating hydroxyapatite, metal-ion doping, and SF-based hydrogel systems. Overall, this review provides comprehensive insights into SF-enhanced Ti scaffolds for next-generation bone repair.
Hydrogels are three-dimensional elastic networks that have applications in wide array of biomedical fields. Hydrogels can be crosslinked via dynamic covalent bonds (DCB) in order to done them with the ability to be injected, to self-heal, and to respond to stimuli. In our previous work, reversible thiol-conjugate crosslinks were used in the preparation of dynamic poly(ethylene glycol) (PEG) hydrogels. Because the equilibrium state of these reversible thiol-conjugate bonds can be shifted by temperature, both thermal and photothermal stimuli were used to induce the gel-to-sol transition of these materials to develop an on-demand pulsatile cargo release. However, the dynamic nature of the crosslinks resulted in rapid gel dissolution that prevented their use for long-term drug delivery. In this work, the hydrogels were complemented with stable thiol-maleimide crosslinks to decrease their dissolution rate and prolong their functional lifetime. Data shows that even a small addition of thiol-maleimide crosslinks significantly stabilizes the hydrogels, providing improved control of cargo release initiated by photothermal stimuli but does not cause a notable difference in cargo release at physiological temperature when compared to the hydrogels lacking the stable thiol-maleimide crosslinks.
Injectable hydrogels offer a minimally invasive approach for cartilage repair, enabling precise defect filling and in situ scaffold formation; however, balancing mechanical strength with stem cell viability and chondrogenic differentiation remains challenging. Here, alginate dialdehyde-gelatin (ADAG) hydrogels are reinforced with cellulose nanofibrils (CNFs) to enhance mechanical performance while retaining injectability, rapid self-healing, and chondroinductive properties. FTIR spectroscopy confirms efficient Schiff base cross-linking between ADA and gelatin, with CNF incorporation preserving chemical integrity. SEM imaging revealed a porous, interconnected architecture, with the 9:1 (ADAG: CNF, v/v) hydrogel exhibiting a more homogeneous and compact network structure, similar to ADAG. Optimization identifies 9:1 and 8:2 ratios as maintaining crosslinking density, while 7:3 ratio slightly disrupts uniformity but retains fast gelation (<5 min) and smooth injectability. CNF reinforcement markedly enhanced mechanical properties, as evidenced by increased storage modulus (0.007 MPa) and compressive modulus (0.006 MPa). The hydrogels exhibit high self-healing efficiency (98%) and support robust proliferation of human bone marrow-derived mesenchymal stem cells. Biochemical and gene-expression analyses show enhanced glycosaminoglycan and collagen deposition, upregulation of chondrogenic markers (SOX9, COL2A1, ACAN), and low COL1A1 expression. Overall, CNF-reinforced ADAG hydrogels combine cytocompatibility, mechanical resilience, injectability, and chondroinductive potential, highlighting suitability for stem cell-mediated cartilage tissue engineering applications.
A motor unit is the functional unit of muscle contraction, consisting of a population of skeletal muscle fibers innervated by axon terminals from a motor neuron. Tissue engineering strategies are being pursued to treat neuromuscular injuries by mimicking aspects of native myofascicular architecture; however, the critical role of innervation in myofiber development is often overlooked. Our group previously developed a pre-innervated tissue-engineered muscle on nanofiber sheets, demonstrating that innervation facilitated myofiber maturation and function in vitro. The current study builds on this framework to biofabricate pre-innervated three-dimensional (3D) bundles of individual myofibers that more closely replicate in vivo architecture. Specifically, we established a methodology to generate centimeter-scale Tissue Engineered Motor Units (TEMUs) comprising aligned myofiber bundles within a collagenous hydrogel and innervated by axons projecting from discrete population(s) of spinal motor neurons. A custom-built polydimethylsiloxane micro-scale channel system facilitated the alignment and self-assembly of myoblasts. The presence of aggregated motor neurons and axonal integration significantly enhanced myofiber maturation and contractility compared to non-innervated controls. We also evaluated the effects of media constituents on myofiber maturation, as assessed by myocyte fusion and sarcomere formation. Importantly, this TEMU biofabrication protocol is fully scalable, generating modular myofiber bundles at least 8 cm in length that can be aligned in parallel to achieve large-scale myofiber macro-bundles. TEMUs address key challenges in muscle tissue engineering by providing a 3D biofidelic platform to study the role of innervation in muscle development and function in vitro, as well as an implantable composite tissue to facilitate muscle replacement after severe trauma.
Injectable cryogels have emerged as a transformative class of biomaterials that combine macroporosity, mechanical resilience, and shape-memory properties to enable minimally invasive therapeutic delivery. Unlike conventional hydrogels, cryogels are fabricated through cryogelation-a sub-zero polymerization process that generates interconnected macropores through ice crystal templating-endowing them with sponge-like elasticity and the ability to withstand extreme compression and recover their original architecture upon injection. Over the past decade, injectable cryogels have evolved from simple porous scaffolds to sophisticated multifunctional platforms incorporating nanocomposites, bioactive molecules, and stimuli-responsive elements for applications spanning bone and cartilage regeneration, stem cell delivery, cancer immunotherapy, and hemostatic wound healing. This review provides a comprehensive and critical analysis of recent advances in shape-memory injectable cryogels, organized around five interconnected themes: (i) the physicochemical mechanisms governing shape-memory behavior and material design strategies, (ii) emerging fabrication approaches including three-dimensional printing-cryogelation hybrids and nanocomposite reinforcement, (iii) cryogel-mediated stem cell delivery and tissue regeneration, (iv) immunomodulatory and vaccine platforms, and (v) hemostatic and wound-healing applications. We critically evaluate how macro-architectural features, mechanical tunability, and biochemical functionalization collectively dictate biological outcomes, and identify key challenges-including scalability, sterilization, regulatory pathways, and clinical translation-that must be addressed to realize the full therapeutic potential of injectable cryogels.
Hydrogel-based dressings are widely used in wound healing. Herein, we report a polyacrylic acid (PAA)/polyvinyl alcohol (PVA) composite hydrogel fabricated via self-catalyzed free radical polymerization, with borax serving as the reinforcing phase. Meanwhile, metal-ligand coordination bonding between tannic acid (TA) and Fe3 + further elevates the crosslinking density of the hydrogel network. Magnetic chitosan microspheres (MCMs) were synthesized by emulsion cross-linking and loaded with two antibacterial agents, namely tetracycline hydrochloride (TH) and berberine hydrochloride (Bbh). The incorporation of MCMs into the hydrogel matrix resulted in the development of a multifunctional composite hydrogel suitable for wound dressing applications. Results demonstrated that the composite hydrogel containing a specific concentration of 4‰ (w/v) borax and 20 mg/mL MCMs exhibited superior performance, including enhanced mechanical strength, improved responsiveness, sustained drug release, and potent antibacterial efficacy. The core novelty of this work lies in the synergistic integration of borax-based mechanical reinforcement, MCM-mediated dual drug loading and sustained release, and the self-catalyzed polymerization system. This innovative structural and functional collaboration effectively optimizes the mechanical stability of the hydrogel dressing and achieves synergistic antibacterial and intelligent responsive therapeutic performances, providing a reliable and high-efficiency candidate for advanced wound care and next-generation wound dressing applications.
Enzyme immobilization is an effective strategy to improve catalyst recovery and operational stability, but conventional approaches are often limited by diffusion resistance, steric hindrance, and insufficient control over the enzyme microenvironment. Hydrogel-based materials are attractive supports because their hydrated, tunable, and porous networks help preserve enzyme conformation while improving substrate diffusion and mass transfer. Here, a gas-shearing microfluidic strategy was developed to fabricate alginate/chitosan hydrogel microreactors for dual-mode lipase immobilization through entrapment and genipin-mediated covalent binding. By tuning gas-liquid shear, microspheres with controllable and narrow size distribution were generated without surfactants or UV-initiated polymerization. Importantly, genipin was introduced as a mild and biocompatible cross-linker to reinforce the alginate/chitosan network and create a stable interfacial microenvironment for enzyme immobilization. Compared with conventional cross-linkers, the milder and more controllable reactivity of genipin is advantageous in preserving enzyme conformation and catalytic performance. The resulting microreactors exhibited enhanced catalytic activity, improved storage stability, and good reusability. After five consecutive cycles, the entrapped and covalently immobilized systems retained 70% and 81% of their initial activity, respectively. These results demonstrate that gas-shearing microfluidics combined with genipin-mediated network reinforcement provides a robust and biocompatible platform for constructing hydrogel-based enzymatic microreactors with improved catalytic performance and operational durability.
Due to the high host specificity of bacteriophages, a single-phage superparamagnetic nanoprobe can only detect one bacterial species at a time. In this study, we developed a series of dual-phage magnetic nanoprobes and performed a series of evaluations to identify the optimal formulation. Phages specific to Staphylococcus aureus and Pseudomonas aeruginosa were chemically conjugated to superparamagnetic iron oxide nanoparticles. The lytic activity of each phage was assessed individually and in combination. Six single-phage nanoprobes and nine dual-phage nanoprobes with different phage loading levels were prepared. The lowest detectable bacterial concentration and the number of bacteria captured by each probe were subsequently determined. We developed a dual-phage superparamagnetic nanoprobe with high sensitivity and a detection limit of 101 CFU/mL for either bacterium. The optimal probe contained 107 PFU/mL of each phage. Increasing the phage loading beyond this level reduced bacterial capture efficiency. Additionally, the number of P-phages that could be conjugated to nanoparticles decreased when a high concentration of S-phages was present. No cross-infection between phages and non-target bacteria was observed, minimizing the risk of false-positive detection.
Degenerative ocular diseases are among the leading causes of visual impairment worldwide and require innovative therapeutic approaches capable of promoting tissue regeneration. In this context, biomaterial-based cell therapies have emerged as promising alternatives, although challenges remain regarding the maintenance of a supportive microenvironment after transplantation. This study developed and characterized a hybrid biomembrane composed of poly(lactic-co-glycolic acid) (PLGA) and decellularized corneal extracellular matrix (dCECM) to provide structural and biochemical support for ocular progenitor cells. PLGA membranes were fabricated and coated with dCECM layers. Their morphological, physicochemical, mechanical, and biocompatibility properties were evaluated. Biocompatibility was assessed using stem cells from the apical papilla (SCAP), periodontal ligament (PDLC), and corneal stroma (CSSC). The capacity of the membranes to preserve ocular progenitor markers (PAX6 and RX) and to exert cytoprotective effects on oxidatively damaged retinal pigment epithelial (RPE) cells was also investigated. Hybrid PLGA-dCECM membranes exhibited suitable thickness, increased hydrophilicity, improved tensile strength, and enhanced cell adhesion without evidence of chemical incompatibility. SCAP and CSSC maintained high expression of ocular progenitor markers, while co-culture with injured RPE cells reduced LDH release and cell death. The PLGA-dCECM biomembrane showed both structural support and bioactive cues, supporting its potential application in ocular regenerative therapies.
Anti-fouling of material surfaces is a major concern in the performance of biomedical materials in biological environments. Surface modification of polymeric materials is an effective strategy for controlling the anti-fouling properties of biomedical materials. Synthetic polymers such as poly(ethylene glycol) (PEG), which exhibit high bioinertness and anti-fouling properties, are widely used. Peptide-based anti-fouling materials are gaining attention because of their biocompatibility, long-term biodegradability, and structural diversity. In this study, we explored the potential of antifreeze protein type I (AFP) from winter flounder as a peptide-based anti-fouling material. AFP possesses a simple α-helical structure of approximately 30 amino acid residues and presents an amphiphilic interface consisting of an ice-binding surface and a hydrophilic surface. We constructed a recombinant AFP that can be modified on a glass substrate and evaluated its anti-fouling properties. The AFP-modified substrates significantly suppressed the adsorption of plasma proteins, such as human albumin, fibrinogen, and fibronectin. Furthermore, adhesion of human ovarian cancer SKOV3 cells and mouse platelets to the substrates was suppressed by AFP modification. Notably, tandem-repeat AFP constructs exhibited high resistance to proteolytic enzymes, such as trypsin. These findings highlight the potential of recombinant AFP as a potential peptide-based anti-fouling material for biomedical applications.
Regenerative medicine, an emerging multidisciplinary field, aims to repair or replace damaged or dysfunctional tissues and organs. Natural polysaccharide hydrogels, characterized by a three-dimensional porous structure analogous to human tissues, have been extensively utilized in biomedical applications. Hydrogels fabricated from natural polysaccharides via photopolymerization enable the formation of scaffolds with precise three-dimensional architectures. Exhibiting excellent biocompatibility, controlled degradability, and tunable mechanical and physicochemical properties, these photopolymerized polysaccharide hydrogels can construct tissue-adaptable microenvironments matching the physiological requirements of specific tissues to support cellular activities and tissue regeneration. Consequently, their applications in tissue engineering and controlled drug release have garnered significant attention, demonstrating considerable potential across various contexts. This review, based on an analysis of domestic and international literature, summarizes the latest research progress on natural polysaccharide-based photocrosslinked hydrogels in regenerative medicine. Emphasis is placed on the specific properties of these hydrogels and their emerging therapeutic applications in tissue regeneration, including skin, bone, and nerve repair.
Clinically small-molecule magnetic resonance imaging (MRI) contrast agents face limitations due to safety concerns, low relaxivity, narrow imaging windows, and restricted targeting capabilities. This study synthesized biocompatible nanogels via the polymerization of N-vinyl caprolactam and vinyl phosphonic acid. The nanogels containing phosphonic acid groups could tightly bind with Mn2+, which could improve the biosafety by preventing the release of free Mn2+. Meanwhile, the strong ligand effect improved the longitudinal relaxivity of encapsulated Mn2+ to 29.8 mM- 1s- 1, which was roughly 3.5 times, 10.6 times, and 6.6 times higher than that of manganese chloride (MnCl2), mangafodipir (MnDPDP) and gadolinium diethylenetriaminepentaacetic acid (Gd-DTPA), respectively. These nanogels exhibited the capability of targeting bone metastases and bone tissues in vivo owing to the phosphonic acid groups. Moreover, these nanogels-based contrast agents prolonged the effective imaging window due to the increased circulation time. They also exhibited a loading capacity for clinical hydrophobic drugs, such as atovaquone (ATO), thereby potentially improving the pharmacokinetics. This work highlights the prospect of poly(vinyl phosphonic acid) based nanogels as multifunctional nanoplatforms for diagnostic and therapeutic applications.
Type 1 diabetes is characterized by autoimmune destruction of pancreatic β-cells, resulting in insulin deficiency and impaired blood glucose regulation. Cell encapsulation using alginate-based hydrogels offers immunoprotection but faces challenges due to low oxygen solubility, compromising cell survival to restore vascularization after implantation. To address this, we developed an alginate hydrogel reinforced with graphene oxide (ALGO) and integrated calcium peroxide (CPO) as an oxygen-releasing system, stabilized with poly-L-lysine (PLL). Physicochemical and mechanical characterization confirmed incorporation of all components and improved elasticity with increasing CPO concentration. Hydrogels maintained structural stability for eight days and released oxygen throughout this period. Biocompatibility assays revealed that ALGO containing 0.25% CPO (0.25CPO) preserved cell viability and proliferation for 96 h, while 1% CPO negatively affected survival. Oxygen consumption analysis showed that 0.25CPO sustained mitochondrial respiration and enhanced maximal respiratory capacity. Glucose-stimulated insulin secretion demonstrated that 0.25CPO maintained functional responsiveness under low and high glucose conditions. These findings indicate that 0.25CPO hydrogels provide controlled oxygen delivery, mechanical stability, and improved biocompatibility, making them a promising platform for pancreatic β-cell encapsulation and future preclinical applications in type 1 diabetes therapy.
In this study, hydrogel systems were investigated as protective carriers for quercetin (Que), a sensitive phytopharmaceutical. Matrix-type calcium alginate microparticles and capsule-type calcium alginate-chitosan microparticles were subjected to processing relevant stresses, including storage at -20°C to 25°C for up to 30 days, repeated freeze-thaw cycling, thermal treatment up to 100°C, ultrasonic irradiation (40-200 W), microwave exposure (50-300 W), and UV irradiation (254 and 365 nm) for up to 60 min. The antioxidant activity of encapsulated Que was quantified using EPR spectroscopy based on DPPH radical-scavenging activity. The results demonstrate that polysaccharide-based carrier design plays key roles in determining payload functional stability under stress. Higher alginate concentrations significantly improved Que protection during frozen storage and high-intensity ultrasonic treatment, while chitosan coating provided additional interfacial shield. The alginate-chitosan system showed markedly enhanced resistance to thermal treatment, repeated freeze-thaw cycles, and microwave irradiation. Under moderate storage conditions (4°C and 25°C) and UV exposure, both alginate matrices and alginate-chitosan capsules exhibited comparable stabilization performance. Overall, this study provides quantitative structure-function insights into the stress-dependent protective behavior of polysaccharides and highlights the potential of polysaccharide-based hydrogels for improving the stability of antioxidant compounds during processing and storage in the food and pharmaceutical industry.
Effective pharmaceutical interventions for treating the secondary damage associated with traumatic brain injury (TBI) are limited due to poor delivery into the brain, insufficient target engagement, and an incomplete understanding of the pathophysiological changes that occur post-impact. Thus, nanoparticles (NP), which have an enhanced permeation and retention-like effect within the perturbed blood-brain barrier, have grown as a potential candidate for treating TBI. We have investigated the antioxidant capacity of thiol-based NP, termed neuroprotective copolymers (NPC3), and their ability to neutralize reactive oxygen species (ROS) and lipid peroxidation products (LPOx). Here, we assessed the efficacy of NPC3 for alleviating the secondary injury cascade in TBI with a specific focus on ameliorating molecular and structural deficits in a mouse controlled cortical impact (CCI) model. NPC3 delivered post-CCI alleviated oxidant burden, reducing both antioxidant enzyme expression and Nrf2 activation. These changes in redox signaling resulted in a shift in metabolic function, with increased AMPK activation with NPC3 treatment. T2-weighted and diffusion magnetic resonance imaging revealed vasogenic edema formation at 30 days post-CCI and alterations in mean diffusivity, which were moderated by NPC3. Furthermore, NPC3 reduced GFAP and Iba1 at multiple impact severities, which positively correlated with urinary 8-isoprostane. Overall, this work shows NPC3 reduced glial reactivity, affected redox metabolism, and ultimately contributed to improvements in structural deficits post-CCI.
