Biomedical materials (Bristol, England)最新文献

Diabetes mellitus (DM) has been associated with complications that affect the skeletal system, such as alterations in bone repair, osteoporosis, and an increased risk of fractures. In this context, the use of biomaterials able to promote osteogenic differentiation and, at the same time, limit the oxidative stress induced by DM offers a novel perspective to ensure the repair of diabetic bone tissue. Since lithium (Li) has been recently identified as a biologically active ion with osteogenic and antioxidant properties, the localized and controlled release of Li ions from bioactive glass-ceramic materials represents a promising therapeutic alternative for the treatment of bone lesions in DM. Thus, the aim of this study was to evaluate the potential osteogenic and antioxidant effects of glass-ceramic microparticles derived from a 45S5-type bioactive glass (Bioglass) containing (% by weight) 45% SiO₂, 24.5% Na₂O, 24.5% CaO, and 6% P₂O₅, in which Na₂O was partially substituted by 5% of Li₂O (45S5.5Li), in an experimental model of type 1 DM (DM1). The results obtained demonstrate, for the first time, that both 45S5 and 45S5.5Li glass-ceramic microparticles possess antioxidant activity and stimulate bone formationin vivoboth under physiological conditions and under experimental DM1 in rats. In this sense, they would have potential application as inorganic osteogenic agents in different strategies of bone tissue regenerative medicine.

Wound healing is a complex and dynamic process supported by several cellular events. Around 13 million individuals globally suffer from chronic wounds yearly, for which dressings with excellent antimicrobial activity and cell viability (>70%, as per ISO 10993) are needed. Excessive use of silver can cause cytotoxicity and has been linked to increasing antimicrobial resistance. In this study, HDI Ag foam was synthesized using a safer hexamethylene diisocyanate-based prepolymer (HDI prepolymer) instead of commonly used diisocyanates like TDI and MDI and substantially lower Ag content than that incorporated in other Ag foams. In vitro characteristics of the HDI Ag foam were evaluated in comparison with leading clinically used foam-based dressings. All dressings underwent a detailed characterization in accordance with industrially accepted BS EN 13726 standards. The HDI Ag foam exhibited highest antimicrobial efficiency againstS. aureusandP. aeruginosa(static condition), with the lowest amount of Ag (0.2 wt%) on the wound contact surface. The extracts from HDI Ag foam showed superior cell viability (>70%), when tested on the L929 mouse fibroblast cell line. Measurements of moisture vapor transmission, fluid handling, physico-chemical and mechanical properties ensured that the HDI foam was clinically acceptable for chronic wound patients.

This work reports a new nano platform made from natural materials for phototherapy (PT) applications. For this purpose, calcium carbonate nanoparticles (NPs) derived from Persian Gulf squid bones as a drug carrier, Syzygium cumini (dye extracted from the fruit of the Persian Gulf trees) as a photosensitizer, and Doxorubicin as a chemotherapy (CHT) drug have been used. In addition, copper NPs were added to the above nanocomposition to increase the efficiency of photothermal (PTT) treatment. For PT, samples were irradiated by an 808 nm laser (1 W cm^-2). The results show that nanocomposites play an influential role in the reactive oxygen species process, and an increase of 21 degrees in temperature during 15 min of laser radiation is effective in photodynamic (PDT)/PTT therapy. The drug loading capacity of the nanocomposite was calculated as 49%. This new nanocomposite for simultaneous PDT/PTT/CHT holds great promise for future cancer treatment due to its excellent potential in treatment and reduced systemic toxicity.

As the incidence of chronic wounds increases, the requirements for wound dressings are rising. The specific aim of this study is to propose a novel gallic acid (GA) functionalized silk fibroin (SF) and gelatin (Gel) composite wound dressing in which GA is used as an antibacterial and wound healing substance. Via electrospinning, SF, Gel, and GA mixed solutions could be conveniently fabricated into a composite nanofiber mat (SF-Gel-GA), consisting of uniform fibers with an average diameter around 134.57 ± 84 nm. The internal mesh structure of SF-Gel-GA provides sufficient drug loading capacity, proper moisture permeability, and proper degradation rate. SF-Gel-GA presents excellent biocompatibility. NIH-3T3 fibroblast cells could adhere and spread stably on the SF-Gel-GA surface with slightly promoted proliferation. In the presence of SF-Gel-GA, the growth of both Gram-positive and Gram-negative bacteria, includingStaphylococcus aureusandPseudomonas aeruginosa, is significantly inhibited in both plate and suspension cultures. A cutaneous excisional mouse wound model proves the efficient ability of SF-Gel-GA to promote wound healing. Compared with pure SF dressing and commercial Tegaderm Hydrocolloid^3Mdressing, the wound closure rate with SF-Gel-GA treatment is significantly improved. The histological assessments further demonstrate SF-Gel-GA could facilitate collagen deposition, neovascularization, and epithelialization at wound sites to promote wound healing. In conclusion, a novel SF-Gel-GA composite wound dressing with efficient wound healing activities have been developed for chronic wound treatment with broad healing potential.

Introduction.Ecological concerns and the depletion of petroleum resources have driven the exploration of biodegradable 3D-printing materials derived from bio-renewable sources, such as polylactic acid (PLA) and polyhydroxyalkanoates (PHA). This study aimed to compare the potential cytotoxic effects of a biodegradable PLA/PHA blend filament, a conventional photopolymer (MED610), and a combination of MED610 with a support material (SUP705) before and after steam sterilization in vitro, with a focus on their application in the production of surgical guides.Materials and Methods.PLA/PHA, MED610, and SUP705 (both in their pure and steam-sterilized forms;n= 6 per group) were assessed for their cytotoxic effects on human fibroblasts using the neutral red uptake assay. Positive controls included zinc diethyldithiocarbamate and zinc dibutyldithiocarbamate, while high-density polyethylene served as a negative control. A stock solution of the extraction medium was used as the vehicle control (VC).Results.Significant differences in cell viability were observed between pure PLA/PHA (1.2 ± 0.24) and MED610 (0.94 ± 0.08) (p= 0.005). However, both materials exhibited non-cytotoxicity, with cell viability exceeding 70% compared to VCs. SUP705 (0.58 ± 0.42) demonstrated significantly reduced cell viability compared to PLA/PHA (p= 0.001) and MED610 (p= 0.007). After steam sterilization, no significant difference in cell viability was noted between MED610 (1.0 ± 0.08) and PLA/PHA (1.2 ± 0.25) (p= 0.111). While both materials remained non-cytotoxic after sterilization, SUP705 (0.60 ± 0.45) exhibited cytotoxic effects compared to MED610 (p= 0.006) and PLA/PHA (p< 0.001). Steam sterilization did not induce significant cytotoxic effects in the investigated materials (p= 0.123).Conclusion.Pure and steam-sterilized PLA/PHA and MED610 were not cytotoxic, supporting their potential use in the production of surgical guides. However, the observed cytotoxicity of SUP705 suggests caution in scenarios requiring sterile conditions, as the removal of support material from complex printed parts may be challenging. The consideration of PLA/PHA is recommended in such settings to ensure biocompatibility.

Zirconia is the most promising implant abutment material due to its excellent aesthetic effect, good biocompatibility and corrosion resistance. To obtain ideal soft tissue sealing, the implant abutment surface should facilitate cell adhesion and inhibit bacterial colonization. In this study, pre-sintered zirconia was placed in a suspension of titania (TiO₂) and zirconium oxychloride (ZrOCl₂) and heated in a water bath for dense sintering. A titania coating was prepared on the zirconia surface and subjected to UV irradiation. The surface morphology, elemental composition and chemical state of each group of samples were analyzed by scanning electron microscope, x-ray energy spectrometer, x-ray photoelectron spectroscopy and x-ray diffraction. The responses of human gingival fibroblasts (HGFs) and common oral pathogensStreptococcus mutans(S. mutans) andPorphyromonas gingivalis(P. gingivalis) to modified zirconia were systematically assessed. Our findings demonstrated that the surface of titania-coated zirconia after UV irradiation produced a large number of hydroxyl groups, and its hydrophilicity was significantly improved. Meanwhile, the UV irradiation also greatly removed the hydrocarbon contaminants on the surface of the titania-coated zirconia. The UV-treated titania coating significantly promoted the proliferation, spreading, and up-regulation of adhesion-related genes and proteins of HGFs. Furthermore, the titania coating irradiated with UV could reduce the adhesion, colonization and metabolic activity ofS. mutansandP. gingivalis. Therefore, UV irradiation of titania-coated zirconia can promote the biological behavior of HGFs and exert a significant antibacterial effect, which has broad clinical application prospects for improving soft tissue integration around zirconia abutments.

The mechanical competence and suturing ability of collagen-based membranes are paramount in guided bone regeneration (GBR) therapy, to ensure damage-free implantation, fixation and space maintenancein vivo. However, contact with the biological medium can induce swelling of collagen molecules, yielding risks of membrane sinking into the bone defect, early loss of barrier function, and irreversibly compromised clinical outcomes. To address these challenges, this study investigates the effect of the crosslinked network architecture on both mechanical and suture-holding properties of a new atelocollagen (AC) membrane. UV-cured networks were obtained via either single functionalisation of AC with 4-vinylbenzyl chloride (4VBC) or sequential functionalisation of AC with both 4VBC and methacrylic anhydride. The wet-state compression modulus (E_c) and swelling ratio (SR) were significantly affected by the UV-cured network architecture, leading up to a three-fold reduction in SR and about two-fold increase inE_cin the sequentially functionalised, compared to the single-functionalised, samples. Electron microscopy, dimensional analysis and compression testing revealed the direct impact of the ethanol series dehydration process on membrane microstructure, yielding densification of the freshly synthesised porous samples and a pore-free microstructure with increasedE_c. Nanoindentation tests via spherical bead-probe atomic force microscopy (AFM) confirmed an approximately two-fold increase in median (interquartile range (IQR)) elastic modulus in the sequentially functionalised (E_AFM= 40 (13) kPa), with respect to single-functionalised (E_AFM= 15 (9) kPa), variants. Noteworthy, the single-functionalised, but not the sequentially functionalised, samples displayed higher suture retention strength (SRS = 28 ± 2-35 ± 10 N∙mm^-1) in both the dry state and following 1 h in phosphate buffered saline (PBS), compared to Bio-Gide® (SRS: 6 ± 1-14 ± 2 N∙mm^-1), while a significant decrease was measured after 24 h in PBS (SRS= 1 ± 1 N∙mm^-1). These structure-property relationships confirm the key role played by the molecular architecture of covalently crosslinked collagen, aimed towards long-lasting resorbable membranes for predictable GBR therapy.

Due to the absence of nerves and blood vessels in articular cartilage, its regeneration and repair present a significant and complex challenge in osteoarthritis treatment. Developing a specialized physical and chemical microenvironment supporting cell growth has been difficult in cartilage grafting, especially when aiming for comprehensive biomimetic solutions. Based on previous research, we have designed a tissue-engineered decellularized living hyaline cartilage graft (dLhCG). The study developed a method to improve the hydrophilicity and stiffness of scaffolds by employing chemical grafting techniques and designed a decellularized hyaline cartilage phenotype matrix scaffold for tissue engineering. Here, we reported a method using 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride /N-hydroxysuccinimide (EDC/NHS) to achieve the grafting of chondroitin sulfate (CS) onto dLhCG, ultimately producing a tissue-engineered hyaline cartilage graft with the CS (dLhCG/CS). Young's modulus measurements revealed that the cross-linked scaffolds exhibited enhanced mechanical properties. We implanted the cross-linked dLhCG/CS scaffolds into the trochlear region of rat joints and evaluated their functionality through histological analysis and biomechanical tests. After 12 weeks, the dLhCG/CS scaffolds demonstrated excellent bioinductive activity comparable to dLhCG. The regenerated tissue effectively maintained a hyaline cartilage phenotype and exhibited similar mechanical properties, playing a crucial role in cartilage regeneration.

Injectable calcium phosphate cement (CPC) offers significant benefits for the minimally invasive repair of irregular bone defects. However, the main limitations of CPC, including its deficiency in osteogenic properties and insufficient large porosity, require further investigation and resolution. In this study, alginate-chitosan-alginate (ACA) microcapsules were used to encapsulate and deliver rat bone mesenchymal stem cells (rBMSCs) into CPC paste, while a porous CPC scaffold was established to support cell growth. Our results demonstrated that the ACA cell microcapsules effectively protect the cells and facilitate their transport into the CPC paste, thereby enhancing cell viability post-implantation. Additionally, the ACA + CPC extracts were found to stimulate osteogenic differentiation of rBMSCs. Furthermore, results from a rat cranial parietal bone defect model showed that ACA microcapsules containing exogenous rBMSCs initially improved thein situosteogenic potential of CPC within bone defects, providing multiple sites for bone growth. Over time, the osteogenic potential of the exogenous cells diminishes, yet the pores created by the microcapsules persist in supporting ongoing bone formation by recruiting endogenous cells to the osteogenic sites. In conclusion, the utilization of ACA loaded stem cell microcapsules satisfactorily facilitate osteogenesis and degradation of CPC, making it a promising scaffold for bone defect transplantation.

The high heterogeneity of neuroblastoma (NB) is currently the main challenge in clinical treatment, impeding the complete eradication of the tumor through monotherapy alone. In this study, we propose a combination strategy using a targeted nano co-delivery system (ADRF@Ag₂Se) comprising phototheranostic agents, differentiation inducers and chemotherapy drugs for sequential therapy of NB. Upon intravenous injection, ADRF@Ag₂Se demonstrates effective tumor targeting by the specific binding of AF7P to MMP14, which is overexpressed on the surface of NB cells. Subsequent implementation of local photothermal therapy (PTT) leverages the robust photothermal conversion capabilities of the amphiphilic photothermal reagent PF. This is followed by the temperature-triggered release of differentiation-inducing agent 13-cis-retinoic acid and chemo-drug doxorubicin to synergistically eliminate the residual lesions. This nanotherapeutic strategy facilitatesin vivotargeted delivery and PTT under the supervision of NIR-II fluorescence, and it also enhances the chemotherapeutic response through differentiation induction of poorly differentiated cancer cells. In the NB tumor model, this co-delivery strategy effectively inhibited tumor growth and significantly prolonged the survival of the mice.