Journal of Biomaterials Applications最新文献

Elevated levels of reactive oxygen species (ROS) in the bone defect area impede bone regeneration and repair. Although titanium and its alloys are widely used for bone defect repair, they lack bioactivity and the ability to scavenge ROS at the defect site, leading to poor osseointegration. To address this, surface modification of Ti alloys with coatings is a common strategy. This study aimed to investigate the osteogenic and antioxidant effects of a novel glutathione (GSH)-coated Ti screw (Ti^GSH) on bone regeneration. Ti^GSH was fabricated using a PDA intermediary layer, followed by chelation with GSH. In vitro studies demonstrated sustained GSH release from Ti^GSH over 15 days. In vivo studies revealed that Ti^GSH did not alter the levels of GSH in the plasma of rats, but it significantly increased the GSH content at the bone defect site. Ti^GSH effectively scavenged DPPH• radicals and reduced intracellular ROS levels in bone marrow mesenchymal stem cells (BMSCs), promoting their proliferation, osteogenic differentiation, and mineralization. In vivo experiments in a rat bone defect model showed that Ti^GSH significantly reduced the level of oxidative stress at the bone defect site, thereby enhancing the bone regeneration and osseointegration capabilities of the titanium screw. Meanwhile, Ti^GSH did not cause any adverse effects in the rats. Overall, Ti^GSH demonstrates promising potential as a biocompatible and osteoinductive material for bone defect repair, with sustained local GSH release mitigating oxidative stress and promoting bone regeneration.

AimOver the past few decades, the prevalence of visual impairments has increased substantially, and some are incurable. This study aimed to present a co-culture method that promotes the differentiation of retinal progenitor cells (RPCs) in the presence of retinal pigment epithelium (RPE) cells.MethodsWe implemented a three-dimensional culture system using a modified alginate substrate to culture human embryonic stem cell-derived RPCs on top of an RPE layer, mimicking an in vivo environment. The characteristics of RPCs in experimental and control groups were analyzed at the RNA and protein levels, and the 3D retinal-like structures were examined by H&E staining. Statistical analysis was conducted in GraphPad Prism (v5.1) using unpaired Student's t-tests and one-way ANOVA.ResultsHypoxic culture conditions better maintained naïve RPC characteristics than normoxic conditions, with significantly higher expression of RAX, LHX2, and PAX6. The addition of Matrigel to simulate the subretinal space supported RPE survival. In this 3D coculture model, RPCs differentiated into neural tube-like structures-potentially due to RPE-secreted inductive factors-and exhibited higher expression of photoreceptor markers than RPCs cultured without RPE.ConclusionOur results demonstrate that a 3D coculture system can be used to investigate the cellular and molecular mechanisms underlying retinal development and to support the formation of 3D retinal structures for future preclinical and clinical applications.

This study describes the derivatization of Rapamycin (Ra) with acryloyl chloride (AcCl) and iodoacetic acid (IAA), yielding hydrolysis-susceptible esters designed for controlled drug release at physiological pH. These esters were further conjugated to thiolated polyethylene glycols (PEGs), yielding compounds with enhanced water solubility, pendant thiol groups and with variation in the number of methylene groups between the ester and thioether moieties. Hydrogels were subsequently formed via conjugate addition reactions using multi-arm PEG macromers, specifically 8-arm PEG acrylates or vinyl sulphones, alongside thiolated PEG crosslinkers. The primary focus was to elucidate the impact of structural modifications surrounding the thioether ester linker on drug release kinetics. In vitro release studies demonstrated zero-order Ra elution over 7-19 days, modulated by gel architecture. Notably, Ra incorporated via α-thioether ester bonds exhibited significantly faster release than their β-thioether ester counterparts, with release rate increases of 11% and 31%, respectively, across the gel assemblies examined. This behavior was attributed to the electron-withdrawing effect of the adjacent thioether group, which enhanced ester hydrolysis. Additionally, creating a hydrogel more prone to swelling and degradation (by using the PEG acrylate multi-arm instead of the PEG vinyl sulphone equivalent) increased the overall drug release rate due to higher water uptake within the gel matrix. An alternative strategy involved Ra-based crosslinking, where Ra, di-functionalized with IAA, acted as a crosslinker for the PEG thiol multi-arm molecules. This assembly exhibited a biphasic release profile, initially mimicking the linear zero-order release of Ra mono-iodoacetic ester crosslinked with PEG acrylates, followed by an exponential burst phase. These findings provide critical insights into hydrogel design strategies for tailoring drug release kinetics, paving the way for advanced controlled drug delivery applications.

Calcium silicate cements (CaSiO₃) are widely used in bone repair treatments for both medical and dental applications. To meet the demands of tissue engineering, three calcium silicate cements were developed: a control group without carbon nanotubes (CNT) and two experimental groups incorporating CNT nanoparticles at concentrations of 0.2% and 0.5%. The surface topography of the calcium silicate-based cements was analyzed using field emission scanning electron microscopy (FEG-SEM) and X-ray diffraction. Additionally, an in vitro cell viability assay was performed to assess cytotoxicity. An in vivo study was also conducted using 24 Wistar rats, where critical bone defects of 3.0 mm in diameter were surgically created in both tibiae using a trephine drill. A clot group was included as a control. Following euthanasia, the samples were evaluated through histological and histomorphometric analyses, and a three-point flexural biomechanical test was performed. Statistical analysis was conducted using one- and two-way ANOVA, with a significance level set at 5%. The results indicated that none of the cements exhibited cytotoxicity. Regarding bone neoformation, the clot group showed significantly lower values compared to the SiCa and SiCa+0.5%CNT (mass) groups (p < 0.05), while the SiCa+0.2%CNT group did not differ statistically from the others (p > 0.05). The biomechanical test revealed a statistically significant difference between the SiCa+0.2%CNT group and the SiCa and SiCa+0.5%CNT groups, with the SiCa+0.2%CNT group exhibiting lower values (p < 0.05), whereas the clot group showed no statistical difference from the other groups (p > 0.05). These findings indicate that the incorporation of carbon nanotubes (CNT) into calcium silicate cements did not result in significant differences in bone tissue regeneration when compared to cements without CNT.

Diabetic wounds are a severe complication of diabetes, imposing a significant economic burden on patients and their families. Egg white (EW) is a natural, cost-effective, and easily accessible nutrient that contains various bioactive compounds with anti-inflammatory and pro-angiogenic properties. Carbon dots (CDs) exhibit excellent biocompatibility and low toxicity. This study introduces a CDs-crosslinked EW hydrogel (CEWH), prepared using CDs as crosslinkers for EW. Our previous study has established CEWH as a multifunctional biomaterial for tissue engineering. In this study, we further demonstrate that CEWH acts as a scaffold for diabetic wound healing in a mouse model by recruiting macrophages and promoting their polarization toward the M2 phenotype, thereby improving the local wound microenvironment. Its large pore size and extended degradation profile facilitate vascular infiltration into the wound site. Moreover, CEWH not only enhances the proliferation of skin tissue cells but also promotes the regeneration of hair follicles, sebaceous glands, and nerves while facilitating collagen deposition, ultimately restoring normal skin architecture and accelerating wound closure in diabetic mice. Overall, our findings underscore CEWH's potential as an effective and affordable wound dressing, providing a safe and economically viable solution for diabetic wound treatment.

Although autografts and allografts remain common for bone defect repair, they entail donor-site morbidity, limited availability, and potential immune rejection. The development of tissue engineering has provided a potential solution to overcome these and facilitate effective bone regeneration. Extensive research has confirmed the osteogenic potential of bioactive molecules like Atorvastatin (ATV) and Icariin (ICA). But despite the increasing body of evidence supporting their individual merits, few studies have investigated the synergistic integration of these materials in Nanocomposite scaffolds. A novel three-dimensional scaffold composed of polycaprolactone (PCL), carboxymethyl chitosan (CMCs), and nano-hydroxyapatite (nHA), co-loaded with Icariin and Atorvastatin, and fabricated using the freeze-casting technique, is described. This study aimed to evaluate the scaffold's effectiveness in promoting calvarial bone regeneration in Wistar rats, contributing to the advancement of biomaterials in bone tissue engineering. Scaffolds containing PCL/CMCs/nHA with 0.1% ICA and 0.1% ATV were fabricated using the freeze-casting method. In vitro assessments were conducted to evaluate the biomechanical and physiological properties of the scaffolds. In vivo experiments involved implanting the scaffolds into calvarial bone defects in six groups of Wistar rats. After 12 weeks, histological analysis was performed to assess bone regeneration, including fibrous tissue formation, bone formation, osteon development, and osteoblast cell numbers and fibroblast cell numbers. After 72 h of incubation, the PCL/CMCs/nHA/ATO/ICA scaffold significantly enhanced cell viability compared to other groups, however, the differences observed between the other groups were not statistically significant. In vivo, results showed significantly greater bone formation, osteon development, and osteoblast numbers in the PCL/CMCs/nHA/ATO/ICA group than in the negative and other groups. The PCL/CMCs/nHA/ATO/ICA scaffold demonstrated superior bone regeneration outcomes, showing comparable performance to autografts in terms of new bone tissue formation, osteon structure, and 72-h cell viability, suggesting its potential as a viable alternative in bone tissue engineering.

One of the disadvantages of traditional ophthalmic formulations is their short residence time in the eye. An in situ gel is recommended as a remedy, as it can be converted into a gel upon contact with the eye and adhere for an extended period. Tamarind seed polysaccharide (TSP) is non thermo-sensitive and possesses the necessary properties to be used as a vehicle for administering medication to the eye. However, the administration of medication into the eyes through TSP based in situ gel has not yet been studied. N-isopropyl acrylamide was grafted onto TSP to make it temperature sensitive. Then, a TSP-based thermo-sensitive in situ gel-forming solution loaded with dorzolamide hydrochloride (2% w/v) was developed and evaluated through in vitro, ex vivo, and in vivo tests. The in situ gel forming solution turns into a gel at 37°C. The safety and efficacy of the formulation were confirmed through an in vivo study on rabbit eyes with induced glaucoma. The findings indicate that the in situ gel significantly reduced intraocular pressure (IOP), with effects comparable to those of marketed eye drops.

Study objectives: We aimed to develop a drug-loaded hydrogel-encapsulated chest drain to improve postoperative comfort and recovery in thoracic surgery patients. Methods: The hydrogel was modified with different ratios of glycerol and alginate, then mixed with varying concentrations of ropivacaine and fixed on a simulated chest drain tube using a mould and calcium chloride solution. The morphology, degradation, and slow-release properties of the hydrogel were assessed to identify the most suitable formulation. A bacteriostatic test was conducted using bacterial smear plates. The new chest drain was then implanted in rats using the seldinger method. Pathological changes were observed with imaging techniques such as chest ultrasound and radiographs, while lung function was assessed to evaluate the analgesic effect. After the animal experiments, hematoxylin and eosin (H&E) and Masson staining were performed on relevant tissues to analyze inflammation, and SOD activity was measured to assess oxidative stress levels. Results: The optimal drug-loaded hydrogel for chest drains contained 2% sodium alginate, 10% glycerol, and ropivacaine concentrations between 0.25% and 0.75%. This formulation showed superior morphological characteristics, degradation, and sustained-release properties. It also exhibited excellent bacteriostatic effects. The low-concentration (0.25%) drug-loaded hydrogel demonstrated better analgesic, anti-inflammatory, and oxidative stress-inhibitory effects in animal studies. Conclusions: The modified ropivacaine-alginate hydrogel-encapsulated chest drain offers a promising local slow-release strategy and may contribute to rapid rehabilitation in thoracic surgery.

Mechanotransduction plays a pivotal role in shaping cellular behavior including migration, differentiation, and proliferation. To investigate this mechanism more accurately further, this study came up with a novel elastomeric substrate with a stiffness gradient using a sugar-based replica molding technique combined with a two-layer PDMS system. The efficient water solubility of candy allows easy release, creating a smooth substrate. By adjusting the substrate's thickness, the optimal effective gradient length for the study is achievable. Additionally, adjusting substrate thickness precisely controls stiffness, from very soft to hard-tissue-like rigidity. Atomic force microscopy characterization confirmed a continuous stiffness gradient on three commonly used PDMS mixtures, 1:30, 1:50, and 1:75, demonstrating the versatility of this method for fabricating and tuning substrates to mimic various tissue environments. In cellular experiments, 3T3 fibroblast cells exhibited a significant migratory response toward the 1:50/1:75 two-layer stiffness gradient, with cells migrating preferably in stiffer directions. Its cost-effectiveness, smooth surface, and ability to regulate gradient substrates with varied stiffness via different PDMS combinations are key advantages. By precisely replicating physiologically relevant mechanical microenvironments, this method advances mechanobiology research and facilitates modeling of stiffness-guided cellular behaviors, paving the way for reliable tissue engineering and regenerative medicine studies.

The eye is an essential sense organ and drug delivery to the eye is a challenging task due to protective barriers that hinder drug penetration. Over 90 percent of treatments for eye diseases are topical, but frequent administration over extended periods can lead to toxicity and compliance issues. Over the years, extensive research has been aimed at developing drug delivery systems that enhance drug bioavailability at the target site while minimizing side effects. Innovative drug carrier systems have been researched and developed to extend retention time, decrease administration frequency, improve therapeutic efficacy, and ensure biocompatibility. In this article, we delve into the various ocular barriers affecting drug delivery and provide an overview of the utilization of biomaterials and nanotechnology in ocular drug delivery. We explore its applications in the treatment and management of various diseases affecting the anterior segment of the eye.