Biomaterials research最新文献

The aim of this study was to determine the effect of membrane fixation and combinations of bone substitute materials and barrier membranes on horizontal bone regeneration in peri-implant defects. Eight mongrel dogs underwent chronic buccal peri-implant dehiscence defects creation and were randomized into 4 groups: (a) deproteinized bovine bone mineral 1 (DBBM1) with a native collagen membrane (CM) (BB group, positive control group), (b) DBBM1 with native CM and 2 fixation pins (BBP group), (c) DBBM2 with a cross-linked CM (XC group), and (d) DBBM2 with cross-linked CM and 2 fixation pins (XCP group). Following 16 weeks of healing, tissues were radiographically and histomorphometrically analyzed. The total augmented area was significantly larger in the BBP, XC, and XCP groups compared to the BB group (4.27 ± 3.21, 7.17 ± 7.23, and 6.91 ± 5.45 mm² versus 1.35 ± 1.28 mm², respectively; P = 0.022). No significant difference for the augmented tissue thickness was observed among the 4 groups. The augmented tissue thickness measured at 3 mm below the implant shoulder was higher in BBP, XC, and XCP than that in BB (2.43 ± 1.53, 2.62 ± 1.80, and 3.18 ± 1.96 mm versus 0.80 ± 0.90 mm, respectively), trending toward significance (P = 0.052). DBBM2 and a cross-linked CM were significantly more favorable for horizontal bone regeneration compared to DBBM1 and a native CM. However, when DBBM1 and a native CM were secured with fixation pins, outcomes were similar. The addition of pins did not lead to more favorable outcomes when a cross-linked CM was used.

Marine-sponge-derived spicule microparticles (SPMs) possess unique structural and compositional features suitable for bone tissue engineering. However, significant challenges remain in establishing their osteogenic mechanism and practical application in animal models. This study explores the biomimetic potential of SPM in orchestrating biomineralization behavior and modulating the Yes-associated protein 1/transcriptional coactivator with PDZ-binding motif (YAP/TAZ) pathway both in vitro and in vivo. Characterization of SPM revealed a structure comprising amorphous silica oxide mixed with collagen and trace amounts of calcium and phosphate ions, which have the potential to facilitate biomineralization. Structural analysis indicated dynamic biomineralization from SPM to hydroxyapatite, contributing to both in vitro and in vivo osteoconductions. In vitro assessment demonstrated dose-dependent increases in osteogenic gene expression and bone morphogenetic protein-2 protein in response to SPM. In addition, focal adhesion mediated by silica diatoms induced cell spreading on the surface of SPM, leading to cell alignment in the direction of SPM. Mechanical signals from SPM subsequently increased the expression of YAP/TAZ, thereby inducing osteogenic mechanotransduction. The osteogenic activity of SPM-reinforced injectable hydrogel was evaluated in a mouse calvaria defect model, demonstrating rapid vascularized bone regeneration. These findings suggest that biomimetic SPM holds significant promise for regenerating bone tissue.

The challenge of delivering therapeutics to the central nervous system due to the restrictive nature of the blood-brain barrier (BBB) is a substantial hurdle in neuropharmacology. Our research introduces a breakthrough approach using microtubule-dependent transcytosis facilitated by novel aqueous compounds. We synthesized a series of red-emitting pyran nitrile derivatives. The molecular structure of compounds, photophysical properties, and water solubility were characterized. BBB permeability of BN1 was assessed in an in vitro BBB model. The transmembrane transport mechanism was next analyzed. The derivative was injected in the wild-type mouse for evaluation of brain penetration and biodistribution in the brain. We further investigated the potential of BN1-functionalized BBB-nonpenetrated silica nanoparticles for brain targeting. This compound demonstrated an ability to form endosomes within the phospholipid layer, thus enabling efficient penetration of the BBB via microtubule-mediated transcytosis, as evidenced in vitro model. This was further confirmed by in vivo experiments that BN1 displays the excellent BBB penetration and retained in brain parenchyma. Furthermore, BBB-impermeable mesoporous silica nanoparticle codelivery system markedly enhanced the transport efficiency to the brain in vivo by BN1-functionalized. These findings indicate that our designed aqueous molecules not only are capable of traversing the BBB but also serve as a viable new strategy for central-nervous-system-targeted drug delivery.

Epigallocatechin gallate (EGCG), a naturally occurring compound known for its multiple health benefits including antioxidant, anti-inflammatory, cancer preventive, and weight management effects, faces challenges due to its inherent instability and limited bioavailability. To address these limitations, our study pioneers an investigation into the unique behavior of EGCG, revealing its degradation into epicatechin (EGC) and gallic acid (GA) during the drug delivery process. In this research, we use fluorescent mesoporous silica nanoparticles (FMSNs) as a sophisticated delivery system for EGCG. This innovative approach aims to not only enhance the stability of EGCG but also regulate its sustained release dynamics to enable prolonged cellular activity. To comprehensively evaluate our novel delivery strategy, we performed assays to assess both the antioxidant potential and its impact on lipid inhibition using Oil Red O. The results not only underscore the potential of FMSN-based nanocarriers for efficient EGCG delivery but also reveal groundbreaking insights into its enzymatic degradation, a previously unexplored facet. This research substantially advances our understanding of EGCG's behavior during delivery and offers a promising avenue for improving its therapeutic efficacy and expanding its applications in health management.

Acute liver failure (ALF) is a complex syndrome that impairs the liver's function to detoxify bilirubin, ammonia, and other toxic metabolites. Bioartificial liver (BAL) aims to help ALF patients to pass through the urgent period by temporarily undertaking the liver's detoxification functions and promoting the recovery of the injured liver. We genetically modified the hepatocellular cell line HepG2 by stably overexpressing genes encoding UGT1A1, OATP1B1, OTC, ARG1, and CPS1. The resulting SynHeps-II cell line, encapsulated by Cytopore microcarriers, dramatically reduced the serum levels of bilirubin and ammonia, as demonstrated both in vitro using patient plasma and in vivo using ALF animal models. More importantly, we have also completed the 3-dimensional (3D) culturing of cells to meet the demands for industrialized rapid and mass production, and subsequently assembled the plasma-cell contacting BAL (PCC-BAL) system to fulfill the requirements of preclinical experiments. Extracorporeal blood purification of ALF rabbits with SynHeps-II-embedded PCC-BAL saved more than 80% of the animals from rapid death. Mechanistically, SynHeps-II therapy ameliorated liver and brain inflammation caused by high levels of bilirubin and ammonia and promoted liver regeneration by modulating the nuclear factor κB (NF-κB) and signal transducer and activator of transcription 3 (STAT3) pathways. Also, SynHeps-II treatment reduced cerebral infiltration of neutrophils, reduced reactive oxygen species (ROS) levels, and mitigated hepatic encephalopathy. Taken together, SynHeps-II cell-based BAL was promising for the treatment of ALF patients and warrants clinical trials.

[This corrects the article DOI: 10.34133/bmr.0002.].

Cancer has become one of the most important factors threatening human health, and the global cancer burden has been increasing rapidly. Immunotherapy has become another clinical research hotspot after surgery, chemotherapy, and radiotherapy because of its high efficiency and tumor metastasis prevention. However, problems such as lower immune response rate and immune-related adverse reaction in the clinical application of immunotherapy need to be urgently solved. With the development of nanodrug delivery systems, various nanocarrier materials have been used in the research of antitumor immunotherapy with encouraging therapeutic results. In this review, we mainly summarized the combination of nanodrug delivery systems and immunotherapy from the following 4 aspects: (a) nanodrug delivery systems combined with cytokine therapy to improve cytokines delivery in vivo; (b) nanodrug delivery systems provided a suitable platform for the combination of immune checkpoint blockade therapy with other tumor treatments; (c) nanodrug delivery systems helped deliver antigens and adjuvants for tumor vaccines to enhance immune effects; and (d) nanodrug delivery systems improved tumor treatment efficiency and reduced toxicity for adoptive cell therapy. Nanomaterials chosen by researchers to construct nanodrug delivery systems and their function were also introduced in detail. Finally, we discussed the current challenges and future prospects in combining nanodrug delivery systems with immunotherapy.

Non-biodegradable implants have undergone extensive investigation as drug delivery devices to enable advanced healthcare toward personalized medicine. However, fibroblast encapsulation is one of the major challenges in all non-biodegradable implants, besides other challenges such as high initial burst, risk of membrane rupture, high onset time, non-conformal contact with tissues, and tissue damage. To tackle such challenges, we propose a novel ultrasoft and flexible balloon-type drug delivery device for unidirectional and long-term controlled release. The ultrasoft balloon-type device (USBD) was fabricated by using selective bonding between 2 polydimethylsiloxane (PDMS) membranes and injecting a fluid into the non-bonded area between them. The balloon acted as a reservoir containing a liquid drug, and at the same time, the membrane of the balloon itself acted as the pathway for release based on diffusion. The release was modulated by tuning the thickness and composition of the PDMS membrane. Regardless of the thickness and composition, all devices exhibited zero-order release behavior. The longest zero-order release and nearly zero-order release were achieved for 30 days and 58 days at a release rate of 1.16 μg/day and 1.68 μg/day, respectively. In vivo evaluation was performed for 35 days in living rats, where the USBD maintained zero-order and nearly zero-order release for 28 days and 35 days, respectively. Thanks to the employment of ultrasoft and flexible membranes and device design, the USBD could achieve minimal tissue damage and foreign body responses. It is expected that the proposed device may provide a novel approach for long-term drug delivery with new therapeutic modalities.

It is urgent to develop an alternative dynamic therapy-based method to overcome the limited efficacy of traditional therapy methods for bladder cancer and the damage caused to patients. Sonodynamic therapy (SDT) has the advantages of high tissue penetration, high spatiotemporal selectivity, and being non-invasive, representing an emerging method for eradicating deep solid tumors. However, the effectiveness of SDT is often hindered by the inefficient production of reactive oxygen species and the nondegradability of the sonosensitizer. To improve the anti-tumor effect of SDT on bladder cancer, herein, a BP-based heterojunction sonosensitizer (BFeSe₂) was synthesized by anchoring FeSe₂ onto BP via P-Se bonding to enhance the stability and the effect of SDT. As a result, BFeSe₂ showed great cytotoxicity to bladder cancer cells under ultrasound (US) irradiation. BFeSe₂ led to a notable inhibition effect on tumor growth in subcutaneous tumor models and orthotopic tumor models under US irradiation. In addition, BFeSe₂ could also enhance T2-weighted magnetic resonance imaging (MRI) to achieve monitoring and guide treatment of bladder cancer. In general, BFeSe₂ sonosensitizer integrates MRI functions for precise treatment, promising great clinical potential for the theranostics of bladder cancer.

Background: Cancer recurrence and metastasis are major contributors to treatment failure following tumor resection surgery. We developed a novel implantable drug delivery system utilizing glycol chitosan to address these issues. Glycol chitosan is a natural adjuvant, inducing dendritic cell activation to promote T helper 1 cell immune responses, macrophage activation, and cytokine production. Effective antigen production by dendritic cells initiates T-cell-mediated immune responses, aiding tumor growth control. Methods: In this study, we fabricated multifunctional methacrylated glycol chitosan (MGC) hydrogels with extended release of DNA/doxorubicin (DOX) complex for cancer immunotherapy. We constructed the resection model of breast cancer to verify the anticancer effects of MGC hydrogel with DNA/DOX complex. Results: This study demonstrated the potential of MGC hydrogel with extended release of DNA/DOX complex for local and efficient cancer therapy. The MGC hydrogel was implanted directly into the surgical site after tumor resection, activating tumor-related immune cells both locally and over a prolonged period of time through immune-reactive molecules. Conclusions: The MGC hydrogel effectively suppressed tumor recurrence and metastasis while enhancing immunotherapeutic efficacy and minimizing side effects. This biomaterial-based drug delivery system, combined with cancer immunotherapy, can substantial improve treatment outcomes and patient prognosis.