Regenerative Biomaterials最新文献

High myopia severely threatens the visual health of adolescents, with pathological features of decreased collagen aggregation and scleral thinning, ultimately leading to axial elongation on preretinal imaging. Fibroblasts play crucial roles in scleral remodelling and myopia prevention. In this work, we developed a fibroblast-loaded carboxymethyl chitosan-aldehyde hyaluronic acid (CMCS-HA-CHO) injectable hydrogel for anti-scleral remodelling. The CMCS-HA-CHO hydrogel is formed through simple mixing under mild conditions via a Schiff base reaction between CMCS and HA-CHO. The CMCS-HA-CHO hydrogel can be injected into a posterior sclera with a low modulus, and the increasing modulus over time provides good mechanical support to the sclera. The hydrogel demonstrated excellent cytocompatibility and haemocompatibility, and the encapsulated fibroblasts maintained good activity. Both the hydrogel and fibroblast-loaded hydrogel effectively shortened the axial length of myopic eyes in guinea pigs in a deprivation model. In particular, the fibroblast-loaded hydrogel had the best therapeutic effect because of the synergy of cell therapy and mechanical support, which always shortened the eye axis within 4 weeks. Furthermore, increased collagen secretion promoted by fibroblasts can increase the thickness of the sclera and improve its biomechanical properties, ultimately repairing the physiological structure of the sclera. This fibroblast-loaded injectable hydrogel may represent a promising clinical approach for controlling myopia progression.

Calcium silicate (CS)-based bioactive materials were widely utilized to promote the therapeutic potential of bone marrow mesenchymal stem cells (BMSCs) in bone tissue engineering. The activation of numerous classic bone formation modulators, including the BMP, Wnt, and MAPK/ERK signaling pathways, contributes to the CS-induced osteogenesis of BMSCs. Mitochondrial metabolic patterns have emerged as key contributors to the osteogenic differentiation of mesenchymal stem cells. However, whether CS affects the mitochondrial metabolic profiles of BMSCs is mostly unclear. Herein, we showed that CS induced the osteogenic differentiation of human BMSCs (hBMSCs) mainly via silicon (Si) ion release. Moreover, CS-stimulated hBMSCs underwent metabolic reprogramming accompanied by increased mitochondrial oxidative phosphorylation (OXPHOS) activity. The inhibition of OXPHOS hindered the CS-induced osteogenic differentiation of hBMSCs and bone regeneration, indicating that CS-induced OXPHOS mediated the observed increase in osteogenesis. Mechanistically, CS induced mitophagy and autophagic flux by increasing the formation of autolysosomes and lysosomal degradation to eliminate dysfunctional mitochondria and mitochondrial reactive oxygen species production, leading to enhanced OXPHOS and osteogenesis in hBMSCs. Furthermore, CS promoted mitochondrial fusion in hBMSCs, which may contribute to OXPHOS activation. Our investigation reveals a previously unclear function of CS in regulating the osteogenesis of BMSCs by inducing mitophagy-mediated metabolic shifts toward OXPHOS.

Chemically crosslinked silk fibroin (SF) hydrogels exhibit excellent extracellular matrix-mimicking features and tunable mechanical characteristics, making them highly promising for 3D cell culture and tissue engineering. However, the protein segments within SF hydrogels can spontaneously undergo a conformational transition from random coil to β-sheet, inducing dynamic changes in the material's mechanical properties and pore structures. Such dynamical material cues could probably have significant effects on cell behaviors, thus inducing a kind of unknown influence which cannot be ignored when applying these hydrogels in 3D cell culture and tissue repair. Based on this, the current research seeks to clearly reveal the impacts of the protein conformational transition microenvironment within SF hydrogels on the proliferation and chondrogenic differentiation of encapsulated stem cells. To this end, this study successfully constructed a series of SF hydrogels with highly similar initial properties but different conformational transition rates, which was enabled by modulating the uniformity of the chemical crosslinking points while fixing the similar crosslinking density. Results showed that the SF hydrogel with lower uniformity of crosslinking points exhibited faster conformational transition rates, and vice versa. Encapsulated mesenchymal stem cells' responses further clearly illustrated that the protein conformational transition microenvironment in SF hydrogels could obviously regulate cell proliferation and chondrogenesis. Specifically, a relatively slower conformational transition rate was more favorable for encapsulated cell proliferation, whereas a moderate transition rate was more beneficial for encapsulated cell chondrogenesis. Related research is expected to expand the knowledge and understanding of the impacts of dynamical protein conformational transition microenvironment on cell behavior within hydrogels, and provide valuable insights for the development of efficient SF-based cell culture matrices and cartilage scaffolds.

Sepsis, a systemic inflammatory response syndrome, causes severe immune dysfunction and is associated with high mortality because of the lack of effective clinical interventions. To address the pathogenesis of sepsis, such as bacterial infection and the exacerbation of inflammation and oxidative stress, an acidity-activated polylysine (PLL)-based copolymer self-assembly (PPDD) was developed. This material was synthesized by conjugating polyethylene glycol-modified PLL (PEG-PLL) with 2,7-dichlorofluorescein diacetate (DCFH-DA). PPDD, with its PLL-derived antibacterial and antioxidant properties, can scavenge reactive oxygen species (ROS), mitigate inflammation and eliminate bacteria. These combined actions help alleviate the symptoms of sepsis and improve survival rates. In vitro and in vivo experiments confirmed that this approach can rapidly neutralize ROS, significantly reduce pro-inflammatory cytokine cascades and effectively clear bacteria, thereby improving physiological stability and survival rates. Notably, Day-14 survival reached 80% in the PPDD-treated group compared with 20% in septic controls. More significantly, when the PPDD copolymer self-assembles into the acidic sepsis microenvironment, it disassembles and reconfigures from a spherical to an ellipsoidal structure. This acidity-activated structural transformation exposes more bioactive components for ROS scavenging, which is beneficial for removing oxidative stress, killing bacteria, reducing inflammation and alleviating sepsis. Following PPDD administration, systemic levels of TNF-α, IL-6, IL-10 and CRP were reduced by 38.1%, 46.0%, 76.7% and 32.9%, respectively, confirming its robust anti-inflammatory effect. Additionally, the conjugated DCFH-DA, a cell-permeable fluorescent probe, enables monitoring of oxidative stress and tracing the evolution of sepsis, especially after treatment. A comprehensive biosafety assay revealed no detectable hemolysis or organ toxicity, substantiating the translational potential of this platform. Our biocompatible and acidic sepsis environment-responsive PPDD paves a solid foundation for the clinical diagnosis and treatment of sepsis.

Periosteum plays an indispensable role in bone regeneration by providing osteogenic and angiogenic cues essential for tissue repair. In cases of severe bone defects or nonunion, autologous vascularized periosteum transplantation remains a highly effective clinical solution. However, its application is restricted by donor site morbidity and limited tissue availability, thereby underscoring the urgent need for artificial periosteum that mimics both the composition and structure of the native counterpart. Among these properties, the topological morphology of the periosteum is believed to be critical, yet its influence on bone regeneration remains insufficiently understood. In this study, biomimetic periosteum membranes composed of coaxially electrospun poly(ε-caprolactone) (PCL) and periosteal extracellular matrix (pECM) were fabricated with either random or aligned nanofiber architectures. Their osteogenic potential was systematically evaluated in vitro and in vivo. Compared to the randomly arranged structure, aligned pECM (aPEC) significantly enhanced the adhesion, alignment, and osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) by activating the ITGB1/PI3K/AKT signaling pathway, whereas these effects were not observed in pure PCL membranes. These findings demonstrate that aligned topological morphology in biomimetic periosteum plays a pivotal role in directing stem cell behavior and promoting bone regeneration. This work provides mechanistic insight and technical guidance for the future design of functionally enhanced artificial periosteum for bone tissue engineering applications.

Pelvic organ prolapse (POP) significantly impacts women's health and quality of life. There is a critical need for alternative biomaterials for surgical POP repair, driven by complications associated with conventional non-absorbable vaginal meshes. As ascorbic acid 2-phosphate (A2P) has been demonstrated to enhance collagen production and cell proliferation in vitro, this study investigated absorbable A2P-releasing poly-l-lactide-co-epsilon-caprolactone (PLCL) membranes in the first in vivo study to evaluate their potential to promote tissue regeneration for POP treatment. Biomaterials (PLCL, PLCL_4%A2P, PLCL_8%A2P and commercial polypropylene (PP) mesh) were implanted subcutaneously on the abdominal fascia of female Sprague-Dawley rats, and tissue samples were collected for tensile testing and histological analysis at 1-week, 1-month and 6-month time points. Histological samples were analysed using X-ray micro-computed tomography, histological stains, and primary antibodies targeting type I and type III collagen to assess connective tissue regeneration and material degradation. The PLCL_A2P groups demonstrated enhanced tissue strength without increased stiffness, compensating for material degradation through tissue regeneration. Moreover, collagen amount was increased in the PLCL_4%A2P and PLCL_8%A2P groups, without signs of adverse fibrosis. Our results suggest that A2P-releasing PLCL_4%A2P and PLCL_8%A2P membranes enhance tissue strength and collagen deposition in vivo, being a potential alternative for POP repair.

Acute liver failure is a life-threatening condition with limited treatment options, primarily liver transplantation, which is constrained by donor shortages and lifelong immunosuppression. This study presents a minimally invasive therapeutic approach using multifunctional microbeads co-encapsulating two cell types: immortalized hepatocytes and umbilical cord-derived mesenchymal stem cells, along with basic fibroblast growth factor-loaded poly(lactide-co-glycolide) microspheres. The alginate microbeads are functionalized with poly(ethylene glycol) and the arginine-glycine-aspartate tripeptide to enhance cell adhesion and are crosslinked via click chemistry for improved structural integrity. The bFGF-loaded PLGA microspheres were synthesized using a double-emulsion solvent evaporation method, achieving an average size of 4.25 ± 2.20 µm, a loading content of 0.078% and an entrapment efficiency of 3.52 ± 0.27%. Sustained bFGF release over 14 days (cumulative 2.39 ± 0.20 ng) enhanced hepatocyte proliferation, human mesenchymal stem cell differentiation and cell viability. Functional assessment demonstrated significantly improved hepatocyte performance, with microbeads producing 2032.53 ± 29.45 ng of albumin and 1057.00 ± 9.19 ng of alpha-fetoprotein over 14 days. Overall, this co-encapsulation strategy enhances hepatocyte regeneration, viability, function and offers a scalable therapeutic platform for ALF. Future studies should optimize the formulation and evaluate long-term efficacy in vivo.

Spinal cord injury (SCI) is a kind of health problem characterized by oxidative stress and neuronal apoptosis, which pose major challenges to the recovery of patients. Recently, the application of photothermal nanotechnology in medicine has opened up exciting new avenues for the treatment of SCI. This innovative approach leverages the unique properties of nanomaterials to enhance therapeutic outcomes. In our study, we developed a novel nanotherapeutic system named ZnO-ZIF8@H, which is designed to deliver targeted neuroprotective effects. We meticulously evaluated its performance under near-infrared (NIR) irradiation, which is known to promote local heating and stimulate biological processes. The data indicated that the application of ZnO-ZIF8@H combined with NIR irradiation significantly reduced oxidative stress levels in the affected tissues. This was evidenced by a marked decrease in malondialdehyde (MDA) levels, a well-known indicator of lipid peroxidation and cellular damage. Simultaneously, the treatment notably enhanced the activity of superoxide dismutase (SOD) and glutathione (GSH) enzymes. These findings suggest that ZnO-ZIF8@H+NIR could both protect cells from oxidative damage and boost the internal antioxidant defenses, highlighting its potential as an effective therapeutic strategy for mitigating secondary injuries following spinal cord trauma. It also suppressed neuronal apoptosis, as evidenced by TUNEL staining and decreased Cleaved-Caspase3 expression in NeuN-positive neurons. These results indicated that ZnO-ZIF8@H+NIR effectively reduces secondary damage from SCI by alleviating apoptosis and oxidative stress, offering a promising approach for the therapy of SCI.

[This corrects the article DOI: 10.1093/rb/rbac072.].

Bone defects rehabilitation is one of the difficulties in oral clinical practice. Implanted biomaterials have pivotal effects on the regeneration in critical bone defects, but the immunologic reactions arising from their entering into the body are difficult to control. Biomaterials characteristics can effect the immune response, and thus, interfere with the skeletal system. Our previous study found that microporous structures on mineralized collagen (MC) modulated macrophage polarization in bone immune response thereby promoting osteogenic differentiation of osteoblasts. However, the role of MC with various microporous structures in guiding bone rejuvenation in vivo is still unknown and the specific mechanism of crosstalk between MC, macrophages and osteoblasts during bone repair is poorly understood. In this research, we investigated the impact and mechanism of MC with different pore sizes on bone regeneration. The results showed that MC with a medium pore size (85 μm) promoted bone defects repair significantly, M2 macrophage polarization and nucleolin (NCL) expression in macrophages. And the fanconi anemia pathway was implicated in this process. We found that NCL regulated macrophage polarization towards M2 by inhibiting and overexpressing NCL in macrophages. This study will provide a new idea for using biomaterials to regulate host immune response and promote bone regeneration.