Biomedical materials (Bristol, England)最新文献

Arteriovenous (AV) shunts are critical conduits for patients with end-stage renal disease undergoing hemodialysis. Desired properties of next-generation AV graft materials include artery-like mechanics, clinically feasible manufacturing processes, and a bioactive interface that facilitates rapid and deep infiltration of neighboring cells to support tissue regeneration. These requirements inspired the design, fabrication, and post-processing of our constructs. In terms of material design, we evaluated the performance of three microfiber graft materials composed of a hydrophobic polymer and photo-clickable, 4-arm thiolated polyethylene glycol-norbornene (PEG-NB). The materials included two coaxially nanostructured fiber designs, each featuring a PEG-NB sheath and different cores-polycaprolactone (PCL) and PCL-co-lactic acid (PLCL), respectively-and a mixed composition created by directly blending the sheath and core solutions during electrospinning. For post-processing, the constructs were either air-dried or freeze-dried (FD). Surface morphology was assessed using scanning electron microscopy, while mechanical properties were characterized through tensile testing and dynamic mechanical analysis. Subcutaneous implants were evaluated at 1, 4, and 16 weeks using histological, immunofluorescent, and multiphoton microscopy analyses to examine cellular distribution, material structure, and tissue remodeling. Results showed that the freeze-drying post-processing method enhanced overall porosity, stiffness, and ultimate tensile strength. Among all tested conditions, the FD core-sheath structure with PCL most closely matched the mechanical properties of native vessels. Using PLCL as a core material increased degradation and cell infiltration during the first month of subcutaneous studies. Ultimately, graft strength, porosity, and bioactivity were effectively modulated by the choice of core material and post-processing method. These findings provide insights into tailoring electrospun PEG-NB hybrid constructs as candidate AV shunt grafts, highlighting opportunities to balance mechanical performance, degradation, and bioactivity for end-stage renal disease patients requiring durable hemodialysis access.

Limited organ availability and transplantation risks have driven the development of tissue engineering approaches. This study developed and characterized crosslinked collagen biomaterial inks extracted from calf skin for three-dimensional bioprinting applications. Collagen was extracted using pepsin digestion and purified through dialysis. Biomaterial inks were prepared at 3%, 4%, and 5% (w/v) concentrations and crosslinked using genipin (1, 3, 5 mM) and riboflavin (1 mM) with UV-A activation. Optimal printing parameters were determined as 5% (w/v) collagen concentration with 0.26 mm nozzle diameter. Synchrotron FTIR spectroscopy confirmed successful crosslinking through characteristic peak shifts in amide regions. Mechanical testing revealed enhanced compressive strength: riboflavin-crosslinked scaffolds (1.5 ± 0.08 MPa) > genipin-crosslinked scaffolds (1.19 ± 0.12 MPa) > uncrosslinked scaffolds (0.66 ± 0.03 MPa). Cell viability assessments demonstrated that genipin crosslinking at 1 mM concentration significantly enhanced fibroblast viability (181.2 ± 29.32% compared to uncrosslinked controls), while higher concentrations exhibited cytotoxic effects. Riboflavin biocompatibility assessment was limited by methodological constraints due to spectral interference, preventing reliable comparative evaluation. These results demonstrate that genipin crosslinking successfully enhances both mechanical properties and biocompatibility at appropriate concentrations, while riboflavin crosslinking provides superior mechanical reinforcement but requires alternative biocompatibility assessment methods for comprehensive characterization.

Intervertebral disc herniation is a leading cause of chronic low back pain, where the avascular nature of the disc limits nutrient transport to resident cells, resulting in cellular dysfunction and matrix degeneration. Enhancing vascular perfusion at the region has therefore emerged as a promising strategy to support disc repair. In this context, the present study aimed to develop a biomimetic, mechanically stable nanofibrous annulus fibrosus (AF) patch capable of sustained nicardipine delivery, while simultaneously supporting mesenchymal stem cell (MSC) viability and chondrogenic differentiation. For this, aligned and random poly(ϵ-caprolactone)/gelatin (75:25) nanofibrous patches were fabricated, with the hypothesis that scaffold architecture would influence both drug release behavior and cellular response. The results showed that the aligned fibers exhibited larger pore size and increased surface hydrophilicity compared to randomly oriented fibers. Nicardipine was efficiently encapsulated and released in a sustained manner over 21 d, with an additional late-stage increase in drug diffusion in aligned scaffolds.In vitroassessment using MSCs confirmed cytocompatibility, and markedly improved cell viability on aligned scaffolds. Overall, the findings demonstrate the potential of aligned, nicardipine-loaded PCL-gelatin nanofibrous AF patches as a dual-function platform for localized drug delivery and AF regeneration following discectomy. Further evaluation using native AF cells and relevantin vivomodels will be essential to determine long-term efficacy and safety.

The clinical use of topical hemostatic agents has become increasingly widespread. While these agents primarily serve to control bleeding, their direct contact with bone and surrounding tissues raises concerns about biological compatibility and potential interference with bone healing and regeneration. Given their growing use in osseous surgical procedures, it is critical to characterize and compare the osteogenic properties of these materials. This study evaluated four commercially available gelatin-based hemostatic sponges: Hemospon®, Clinix®, Gelatamp®, and Octocolagen®, for their osteogenic potential. Leachables derived from each sponge were prepared according to ISO 10993-12:2021 guidelines and tested at 12.5% and 50% concentrations inin vitroassays using human osteoblastic populations. Assessed parameters included metabolic activity, proliferation, osteogenic gene expression, alkaline phosphatase (ALP) activity, and extracellular matrix production. Additionally, intact sponges were directly applied to bone defects in anex vivoorganotypic bone culture model, enabling the tissue characterization within a physiologically relevant environment. Results demonstrated marked material-dependent differences. Gelatamp® significantly enhanced osteogenic gene expression, ALP activity, and matrix productionin vitro, and promoted mature collagen depositionex vivo. Hemospon® also showed favorable, though more limited, effects. Octocolagen® exhibited a neutral biologically profile, while Clinix® consistently impaired osteoblastic activity, gene expression, and extracellular matrix formation in both models. These findings demonstrate that gelatin-based hemostatic agents are not biologically equivalent. Material composition and processing influence their regenerative performance, underscoring the need for informed selection when used in bone-contact surgical applications.

Infected wound healing environments present dual challenges of microbial colonization and sustained oxidative stress, critically impairing patient outcomes. Developing advanced dressings capable of concurrent broad-spectrum antimicrobial action and redox homeostasis restoration remains an urgent clinical priority. Here, we engineered a multifunctional porcine small intestinal submucosa extracellular matrix dressing (i.e.SISTP) integrated with AI-screened antimicrobial peptides (AMPs) via tea polyphenol-mediated coordination. The CRRI6 hexapeptide (Arg-Trp-Trp-Arg-Trp-Phe) demonstrated prolonged release kinetics (>6 h) from the SISTP scaffold, achieving ⩾90% eradication ofE. coliandS. aureus. Radical scavenging assays confirmed SISTP's capacity to neutralize reactive oxygen species, whilein vivostudies revealed accelerated wound recovery in infected rat models through synergistic microbial clearance and oxidative stress mitigation. This study pioneers a bio-inspired strategy leveraging AI-optimized AMPs and polyphenol nanoengineering to address the multifactorial pathophysiology of chronic wounds.

The structure of silk fibroin (SF) is similar to that of collagen, making it a commonly used template for mineralisation, nucleation, and growth of hydroxyapatite (HAp). However, the structure of SF has characteristics of high brittleness and poor toughness, which limits the application of pure SF as mineralisation material and needs modification. In the present work, we prepared a dual cross-linked composite scaffold (SCS) of SF and carboxymethyl chitosan (CMCS) through electrostatic attractions and ethylene glycol diglycidyl ether (EGDE)-bridged cross-links. The introduction of CMCS addressed the deficiencies of SF and provided more nucleation sites for HAp, enhancing the ability of the material to induce HAp formation, and thus better supporting cell attachment, proliferation, and differentiation. The results demonstrated successful HAp formation on mineralised scaffolds (SCS/25B and SCS/50B), with SCS/25B exhibiting optimal porosity (∼85.96%), suitable degradation rate (∼38.33%), favourable compressive strength (∼46.05 kPa), and high swelling capacity (∼1381%), meeting key requirements for porous scaffolds. Notably, SCS/25B significantly enhanced MC3T3-E1 cell proliferation, adhesion, and osteogenic differentiation (Alkaline phosphatase activity, and gene/protein expression of Runx2, OPN, OCN) compared to controls.In vivoanimal studies confirmed no significant visceral toxicity in rats. Moreover, implantation of SCS/25B scaffolds for four weeks led to substantial new bone formation at the defect site. In conclusion, dual-SCS exhibits potential as a material for bone tissue engineering and provides insights into the design of SF-based biomimetic mineralisation materials.

The use of covered self-expandable metal (CSEM) stents for fistulas sealing is a common clinical approach. However, these stents need to be removed once their therapeutic goals are achieved. Our study designed and fabricated a dumbbell-shaped, high-porosity, biodegradable polydioxanone weaving tracheal (PW) stent, and investigated its sealing efficacy and degradation characteristics. A tracheal defect model was created in 24 beagle dogs. Six dogs were implanted with CSEM stents, while the remaining 18 dogs received PW stents. The dogs in the CSEM and PW groups were observed for up to 8 and 14 weeks, respectively, with clinical symptoms, tracheoscopy, computed tomography scans, and fluoroscopy monitored. Subsequently, the stents were retrieved to observe morphological changes, and measure mechanical properties. The PW stents exhibited excellent airtightness, with significantly fewer complications such as stent displacement and granulation tissue hyperplasia compared to the CSEM stents. The tracheal tissue response to the PW stent was relatively mild. After PW stent implantation, collagen fiber deposition at the defect site gradually increased, and cartilage structure regeneration was observed in later stages. Notably, cilia were largely absent in the tracheal epithelium, with squamous metaplasia observed even in the later stages of the experiment following PW stent implantation. Additionally, the PW stents remained mostly intact in the canine airways until week 12, and were completely degraded and disappeared from the canine airways at week 14, without causing severe complications. The PW stent, featuring excellent biocompatibility and uniform degradation in the large-animal airway, demonstrated clinical effectiveness in sealing tracheal defects.

Traumatic bleeding and tissue damage pose complex clinical challenges requiring rapid hemostasis and concurrent tissue regeneration. Although traditional hemostatic agents primarily focus on controlling bleeding, they generally lack additional functionalities such as preventing adhesion and promoting tissue regeneration, limiting their clinical utility. This study developed a composite regenerative hemostatic agent based on a porcine decellularized extracellular matrix (ECM) to address these limitations. This agent is designed to achieve rapid hemostasis, prevent adhesions, and promote tissue regeneration. Its functionality was evaluated using a mouse liver laceration model to explore its clinical applicability. Hemostatic efficacy was assessed by measuring the bleeding time and blood loss, and comparing the composite agent with conventional commercial hemostatic agents. Additionally, the degree of adhesion between the liver and surrounding tissues was evaluated after re-opening the abdomen to confirm the anti-adhesion effects. Tissue regeneration and inflammatory responses at the injury site were further analyzed using hematoxylin and eosin staining, Masson's trichrome (MT) staining, and Ki-67 immunohistochemistry. The ECM-based hemostatic agent significantly reduced the bleeding time compared to conventional products and markedly reduced adhesion formation. In the experimental group, the agent enhanced cell attachment and proliferation at the damaged tissue site, to facilitate the natural tissue regeneration process, without inducing inflammatory or pathological changes. The developed composite hemostatic agent could overcome the limitations of existing products by integrating three crucial functions: rapid hemostasis, preventing adhesion, and promoting tissue regeneration. These findings suggest the potential for hepatocyte proliferation and tissue remodeling, which require further validation, and indicate promising applicability in complex surgical environments.

Regenerating injured bone tissue remains a critical challenge, necessitating the development of functional scaffolds to support the intricate process of neo-bone growth. Various natural and synthetic materials combined with bioactive factors have been explored, but decellularized extracellular matrices (dECM) continue to stand out as excellent scaffolding materials due to their intrinsic bioactivity. In this study, we fabricated cryogel-type scaffolds with interconnected pores from decellularized bone ECM (DBM) after mineral removal. To enhance their angiogenic and osteogenic properties, we incorporated laponite (LAP), which is a kind of lithium magnesium silicate. For improved mechanical strength, the DBM was modified with methacrylic anhydride to enable chemical crosslinking among collagen macromolecules. The addition of LAP further contributed to mechanical reinforcement. The resulting composite cryogel demonstrated exceptional cyclic compressive stability, maintaining structural integrity and mechanical strength under repetitive loading.In vitroassays revealed its significant promotion of vascularization and osteogenic differentiation.In vivostudies using a rat cranial defect model confirmed substantial new bone formation and enhanced regeneration of vascularized bone tissue. These findings highlight the potential of bone-derived dECM materials for effectivein situbone regeneration.

Mesoporous silica nanoparticles (MSNs) have been demonstrated to promote osteoblast differentiation; however, the unclear impact of their surface roughness on osteogenesis, coupled with inadequate targeting capability and suboptimal therapeutic outcomes, presents major challenges. Herein, we developed a biomimetic nanoplatform, CM@DEX-R-MSN, by coating dexamethasone (DEX) loaded-rough MSN (R-MSN) with mesenchymal stem cell (MSC) membranes (CM) to enhance osteogenic differentiation of MSCs for improved bone regeneration. The CM@DEX-R-MSN showed retained rough surfaces with a hydrodynamic diameter of 164.35 ± 5.81 nm, a Zeta potential of -11.98 ± 1.37 mV with good MSC membrane integrity, negligible cytotoxicity bothin vitroandin vivo. CM@DEX-R-MSN exhibited significantly enhanced MSC internalization compared to uncoated MSN. They markedly upregulated alkaline phosphatase activity, osteogenic markers, and mineralization nodule formationin vitro. In bone defect model established in rabbits, CM@DEX-R-MSN restored bone volume and prolonged retention at the defect site. More importantly, we experimentally observed that both R-MSN and CM-coated nanoparticles exhibited superior osteogenic differentiation effects compared to conventional MSNs and non-coated counterparts, respectively-with CM@DEX-R-MSN demonstrating the most potent efficacy. Our results demonstrated that CM@DEX-R-MSN synergistically integrates MSC membrane-mediated homotypic targeting, nanotopography of R-MSN, and DEX-driven osteogenic differentiation, offering a promising targeted therapeutic strategy for bone regeneration. Their enhanced biocompatibility, osteogenic efficacy, and sustained retention underscore its translational potential for orthopedic applications.