Journal of biomedical materials research. Part A最新文献

Spinal cord injury (SCI) severely compromises neural regeneration due to limited intrinsic repair capacity. Combining induced pluripotent stem cell (iPSC)-derived organoids with biomaterial scaffolds offers a promising regenerative strategy. This study investigated the therapeutic potential of human spinal cord organoids (hSCOs) encapsulated within gelatin methacryloyl (GelMA) hydrogel for SCI repair. hSCOs were generated from iPSCs via stage-specific patterning (dorsoventral inhibition followed by retinoic acid/SAG-induced motor neuron specification) and encapsulated in GelMA hydrogel. The therapeutic efficacy of hSCOs/GelMA composites was evaluated in a rat T10 contusion SCI model (n = 6/group: Sham, SCI, GelMA-only, GelMA+hSCOs). Functional recovery was assessed weekly for 4 weeks using Basso-Beattie-Bresnahan (BBB) locomotor scores and inclined plane tests. Histological (H&E, Nissl) and immunofluorescence analyses (Tuj1, GFAP, NF200, CD68) quantified tissue repair, neuronal regeneration, astrogliosis, and neuroinflammation at the lesion site. hSCOs expressed key spinal cord markers (OLIG2, NKX6.1, Tuj1, Islet1) and maintained high viability within GelMA hydrogels. Implantation of GelMA+hSCOs composites significantly enhanced functional recovery (improved BBB scores and inclination angles) and reduced lesion volume compared to both SCI and GelMA-only controls. Immunofluorescence revealed that GelMA+hSCOs treatment promoted neuronal integration (increased density of Tuj1⁺ neurons and NF200⁺ neurofilaments), attenuated astrogliosis (reduced GFAP⁺ scarring), and suppressed neuroinflammation (decreased CD68⁺ macrophages) at the injury epicenter relative to control groups. The integration of iPSC-derived hSCOs with GelMA hydrogel significantly promotes structural and functional recovery after SCI by facilitating neuronal survival and integration, mitigating glial scar formation, and modulating the inflammatory response. This combinatorial organoid-hydrogel approach demonstrates substantial translational potential for neural repair strategies.

Tissue engineering and regenerative medicine approaches are being actively developed for degenerative disorders, including osteoarthritis (OA). Decellularized matrix (dECM) is a promising biomaterial; however, glycosaminoglycan (GAG) loss during decellularization limits its chondrogenic potential. In this study, we aimed to overcome this by developing a dECM hydrogel originating from cartilage, functionalized with the GAG chondroitin sulphate (CS), to replenish those originally depleted and incorporating quercetin to enhance hydrogel properties and chondrogenesis. An optimized decellularization protocol efficiently removed DNA, but with a significant loss of GAGs (73%). After dECM solubilization, functionalization with CS or aldehyde modified CS (mCS) was performed. CS-functionalized hydrogels maintained low stiffness compared to non-functionalized hydrogel, while 0.2 mg/mL mCS hydrogels exhibited significantly slower gelation kinetics. To aid the hydrogel's chondrogenic ability, a novel approach using quercetin was investigated. Incorporation of 0.3 mg/mL quercetin in 0.4 mg/mL mCS-functionalized hydrogels resulted in increased gel stiffness. The impact on cell viability and chondrogenic differentiation was evaluated. Results showed similar cell viability in dECM and CS-functionalized hydrogels at 1 and 3 days of culture, with no significant changes in gene expression of chondrogenic and hypertrophic genes. In quercetin-containing hydrogels, the viability of human dermal fibroblasts was not significantly different from non-functionalized hydrogels, while human chondrocytes showed a significant upregulation of collagen type II, with 6.6- and 2.2-fold increases for 0.15 and 0.3 mg/mL quercetin, respectively. These results provide an initial proof-of-concept for dECM functionalization strategies that restore lost CS while incorporating quercetin, creating a microenvironment favorable for cartilage repair.

Thyroid-associated ophthalmopathy (TAO) is an inflammatory orbital disease linked to thyroid dysfunction, leading to fibrosis and adipogenesis, which compromise visual acuity and quality of life. Triamcinolone acetonide (TCA) is effective in managing inflammation; however, it is limited by delivery challenges and side effects. This study evaluates TCA-loaded biodegradable microspheres (TCA@MS) as a controlled-release system to improve TCA's therapeutic efficacy in TAO. It was hypothesized that TCA@MS would enhance drug uptake, reduce fibrosis, and inhibit adipogenesis in TAO models. The TCA@MS was prepared and characterized for drug loading and release, showing 95% release within 7 days. The average diameter of TCA@MS is approximately 365 nm. The TCA@MS demonstrated a drug loading efficiency of approximately 10% and an encapsulation efficiency of around 55%. In vitro, TCA@MS enhanced TCA uptake, reduced fibrosis marker levels, and inhibited adipogenic differentiation in transforming growth factor beta 1 (TGF-β1)-induced human orbital fibroblasts (OFs). In vivo, TCA@MS intraorbital injection treatment of TAO mice decreased adipose tissue, inflammatory cell infiltration, and collagen deposition more effectively than free TCA intraorbital injection treatment. The fibrosis (CTGF, collagen I), proliferative marker (ki-67), and adipogenesis markers (PPARγ) were also downregulated by TCA@MS treatment in TAO mice. These findings suggest that TCA@MS offers a promising delivery system for localized treatment of TAO, providing sustained therapeutic effects with reduced adverse outcomes.

Bone and cartilage tissue have known piezoelectric properties, which means the tissues can generate electrical activity in response to mechanical deformation. Piezoelectricity may be an important physical cue for regenerating tissues. However, biodegradable, biocompatible piezoelectric materials that can be used as tissue engineering scaffolds are limited. In this study, a biodegradable, piezoelectric scaffold was developed where zinc oxide (ZnO), which has known piezoelectric properties, was fabricated into a 3-D fibrous scaffold consisting of polycaprolactone (PCL), a slow-degrading biopolymer, with embedded ZnO nanoparticles (10 wt.%). The ZnO-PCL scaffold was then corona poled in order to improve its piezoelectric activity. The d₃₃ piezoelectric coefficient was 0.21 + 0.05 pC/N for poled ZnO-PCL scaffold. ZnO-PCL and ZnO-PCL-poled composite scaffolds were investigated for promoting human mesenchymal stem cell (MSC) growth and differentiation while subjected to physiological loading without inductive factors in the culture media. Comparisons were made with a PCL control scaffold. Under dynamic compression conditions, the ZnO-PCL group had higher cell growth and promoted chondrogenic differentiation as demonstrated by significantly higher collagen type II and GAG production and gene expression for Sox-9 as compared to PCL control and ZnO-PCL-poled scaffolds, whereas MSCs on ZnO-PCL-poled scaffolds underwent osteogenic differentiation as indicated by significantly higher collagen type I and VEGF-A production. Cells on ZnO-PCL-poled scaffolds also had alkaline phosphatase activity, although not significantly different from the PCL control and ZnO-PCL groups. This study demonstrates ZnO composite scaffolds hold promise as a tissue engineering strategy for osteochondral tissue engineering.

Diabetic wound ulcers, characterized by chronic infection and persistent inflammation, significantly impair patient quality of life and present substantial socioeconomic burdens. Traditional therapeutic strategies frequently encounter challenges, including antibiotic resistance, systemic side effects, and inadequate control over localized inflammation. We herein developed novel carrier-free nanoparticles (CeCur NPs) by self-assembling chlorin e6 (Ce6) and curcumin, achieving simultaneous photodynamic antibacterial activity and sustained anti-inflammatory effects. CeCur NPs exhibited effective and synergetic anti-bacteria and anti-inflammation both in vitro and in vivo. Comprehensive biosafety evaluations further confirmed the excellent biocompatibility of CeCur NPs, underscoring their potential as a promising therapeutic strategy for accelerating diabetic wound healing.

Glutathione (GSH), a pivotal regulator of cellular redox homeostasis, requires precise monitoring for clinical diagnostics. This work develops bovine serum albumin-templated gold nanoclusters (BSA-AuNCs) through in situ chloroauric acid reduction, exhibiting orange fluorescence (λ_em = 610 nm) with 35.8% quantum yield. Systematic evaluation of pH-dependent and time-resolved quenching behavior revealed optimal GSH detection at physiological pH 7.4 within 3 min. The nanozyme demonstrated linear responsivity from 10 nM to 3 μM (Limit of Detection, LOD = 8.7 nM) and validated applicability in biological matrices (urine/serum) with 98.0%–103.3% recovery rates. This photoluminescent platform enables reliable GSH biomarker quantification, advancing point-of-care testing for oxidative stress disorders.