Materials science & engineering. C, Materials for biological applications最新文献

Conventional applications of transplant technology, applied to severe traumatic injuries of the nervous system, have met limited success in the clinics due to the complexity of restoring function to the damaged tissue. Neural tissue engineering aims to deploy scaffolds mimicking the physiological properties of the extracellular matrix to facilitate the elongation of axons and the repair of damaged nerves. However, the fabrication of ideal scaffolds with precisely controlled thickness, texture, porosity, alignment, and with the required mechanical strength, features needed for effective clinical applications, remains technically challenging. We took advantage of state-of-the-art 2-photon photolithography to fabricate highly ordered and biocompatible 3D nanogrid structures to enhance neuronal directional growth. First, we characterized the physical and chemical properties and proved the biocompatibility of said scaffolds by successfully culturing primary sensory and motor neurons on their surface. Interestingly, axons extended along the fibers with a high degree of alignment to the pattern of the nanogrid, as opposed to the lack of directionality observed on flat glass or polymeric surfaces, and could grow in 3D between different layers of the scaffold. The axonal growth pattern observed is highly desirable for the treatment of traumatic nerve damage occurring during peripheral and spinal cord injuries. Thus, our findings provide a proof of concept and explore the possibility of deploying aligned fibrous 3D scaffold/implants for the directed growth of axons, and could be used in the design of scaffolds targeted towards the restoration and repair of lost neuronal connections.

The reason for low- or non-immunogenicity of fish collagens is still in doubt, which, to some extent, bottlenecks their production and clinical application as biomaterials. Employing bovine or porcine type I collagens (BCI or PCI) as controls in this paper, we intensively investigate the influence of tilapia type I collagens (TCI) on the function of dendritic cells (DCs) and T cells. From bio-informatic analyses, as well as data obtained in vitro and in vivo, we find the variations in amino acid sequences lead to only one calcium binding motif in the secondary structure of TCI, compared with three in BCI or PCI. So when TCI (together with the minor amount of Ca²⁺ they take) are uptaken, intracellular [Ca²⁺] remains stable and DCs maintain immature. On the contrary, those that have uptaken PCI or BCI experience not only increased [Ca²⁺] in the plasma but also phosphorylation of p65, resulting in activation of STIM1-Orai1/NF-кB signaling pathway and DC maturation. We fully prove our results on mice models, with no obvious cellular and humoral immune reactions. Our study primarily reveal the underlying mechanisms why TCI, different from BCI or PCI, show almost non-immunogenicity. Our findings are of great importance for the promotion and wide application of TCI in biomedicine.

Photodynamic therapy (PDT) uses a photosensitizer, molecular oxygen, and visible light as an alternative clinical protocol against located malignant tumors and other diseases. More recently, PDT has been combined to immunotherapy as a promising option to treat metastatic cancer. However, previous generations of photosensitizers (PSs) revealed clinical difficulties such as long-term skin photosensitivity (first generation), the need for drug delivery vehicles (second generation), and intracellular self-aggregation (third generation), which have generated a somewhat confusing scenario in PDT approaches and evolution. Recently, metal-organic frameworks (MOFs) with exceptionally high PS loading as a building unit of MOF framework have emerged as fourth-generation PS and presented outstanding outcomes under pre-clinical studies. For PS-based MOFs, the inorganic building unit (metal ions/clusters) plays an important role as a coadjuvant in PDT to alleviate hypoxia, to decrease antioxidant species, to yield ROS, or to act as a contrast agent for imaging-guided therapy. In this review, we intend to carry out a broad update on the recent history and the characteristics of PS-based MOFs from basic chemistry to the structure relationship with biological application in PDT. The details and variables that result in different photophysics, size, and morphology, are discussed. Also, we present an overview of the achievements on the pre-clinical assays in combination with other strategies, including alleviating hypoxia in solid tumors, chemotherapy, and the most recent immunotherapy for cancer.

Surfaces with desirable cytocompatibility and bactericidal ability are favoured for orthopaedic implants to stimulate osteogenic activity and to prevent implant-associated infection. In this work, we creatively introduce ultrasonic vibration (UV) to micro-arc oxidation (MAO) process and explore its influence on the microstructure, corrosion property and biological responses of Zn-modified TiO₂ coating. With the introduction of UV, a uniform surface layer with homogeneously-distributed clusters could be produced as the outer layer, which possesses a fusion band with the underlying TiO₂. The microstructural modification associated with UV results in the enhanced corrosion resistance, increased adhesive strength and improved biological performances of the resultant coating relative to that with the absence of UV. Hence, the ultrasonic auxiliary micro-arc oxidation (UMAO) is regarded as a promising surface modification method to produce Ti-based orthopaedic implants of high quality.

The skin possesses an epithelial barrier. Delivering growth factors to deeper wounds is usually rather challenging, and these typically restrict the therapeutic efficacy for chronic wound healing. Efficient healing of chronic wounds also requires abundant blood flow. Therefore, addressing these concerns is crucial. Among presently accessible biomedical materials, tailored hydrogels are favorable for translational medicine. However, these hydrogels display insufficient mechanical properties, hampering their biomedical uses. Cold-atmospheric plasma (CAP) has potent cross-linking/polymerizing abilities. The CAP was characterized spectroscopically to identify excited radiation and species (hydroxyl and UV). CAP was used to polymerize pyrrole (creating Ppy) and crosslink hybrid polymers (Ppy, hyaluronic acid (HA), and gelatin (GEL)) as a multimodal dressing for chronic wounds (CAP-Ppy/GEL/HA), which were used to incorporate therapeutic platelet proteins (PPs). Herein, the physicochemical and biological features of the developed CAP-Ppy/GEL/HA/PP complex were assessed. CAP-Ppy/GEL/HA/PPs had positive impacts on wound healing in vitro. In addition, the CAP-Ppy/GEL/HA complex has improved mechanical aspects, therapeutics sustained-release/retention effect, and near-infrared (NIR)-driven photothermal-hyperthermic effects on lesions that drive the expression of heat-shock protein (HSP) with anti-inflammatory properties for boosted restoration of diabetic wounds in vivo. These in vitro and in vivo outcomes support the use of CAP-Ppy/GEL/HA/PPs for diabetic wound regeneration.

Efficient and selective targeting of inflamed tissues/organs is critical for diagnosis and therapy. Although nanomaterials themselves have an intrinsic advantage due to their size for targeting inflammation sites, additional functionalization of the nanomaterials with proper targeting moieties is desired to enhance the targeting efficiency. In this study, we aimed to improve the inflammation targeting characteristics of a pluronic-based nanocarrier, which has advantages as a nanosized delivery cargo for diverse molecules, by conjugating with chitosan and ZnBPMP (two Zn(II) ions chelated 2,6-bis[(bis(2-pyridylmethyl)amino)-methyl]-4-methylphenol) moiety. Specific and significant cellular uptake and interaction between the nanocarrier functionalized with ZnBPMP ligand and chitosan to an apoptosis-induced immune cell line were observed in vitro. An inflammation model in the mouse ear caused by skin hypersensitivity was used to evaluate the effect of functionalization with chitosan and ZnBPMP moiety by comparing with various control groups. Functionalization of the nanocarrier with chitosan greatly enhanced the in vivo circulation time of the nanocarrier, so prolonged targeting ability of the nanocarrier to the inflamed ear was achieved. Additional ZnBPMP functionalization to chitosan-functionalized nanocarrier also resulted in significantly improved initial targeting and further enhancement in the targeting until 5 days to the inflamed ear and the decreased non-specific accumulation of the nanocarrier to the remaining body. Thus, developed nanocarrier has a high potential as a drug delivery carrier as well as a diagnostic agent to the inflammation sites.

Cell microenvironment is a collection of dynamic biochemical and biophysical cues which functions as the key factor in determining cell behavior. Encapsulating single cell into micrometer-scale hydrogels which mimics the cell microenvironment can be used for single cell analysis, cell therapies, and tissue engineering. Here, we developed a microfluidics-based platform to engineer the niche environment at single cell level using alginate microgels crosslinked by different metal ions to regulate stem cell behavior for bone regeneration. Specifically, we revealed that Ca²⁺ in the engineered microenvironment promoted osteogenic differentiation of encapsulated stem cells and substantially accelerated the matrix mineralization compared to Sr²⁺ in vitro. However, the superior osteoinductive capacity of Ca²⁺ compared with Sr²⁺ led to comparable bone healing in a rat bone defect model. This attributed to Sr²⁺ in microgels to inhibit the osteoclast activity and bone resorption after implantation. In summary, the present study demonstrates metal ions as a critical factor in the environmental cues to affect cell behavior and influence the efficacy of stem cell-based therapy in tissue regeneration, and provides new insights to engineer an expecting microenvironment for regenerative medicine.

3D-printing technology allows the automated and reproducible manufacturing of functional structures for tissue engineering with customized geometries and compositions by depositing materials layer-by-layer with high precision. For these purposes, the production of bioactive gel-based 3D-scaffolds made of biocompatible materials with well-defined internal structure comprising a dual (mesoporous and macroporous) and highly interconnected porosity is essential. In this work, aerogel scaffolds for bone regeneration purposes were obtained by an innovative strategy that combines the 3D-printing of alginate-hydroxyapatite (HA) hydrogels and the supercritical CO₂ drying of the gels. BET and SEM analyses were performed to assess the textural parameters of the obtained aerogel scaffolds and the dimensional accuracy to the original computer-aided design (CAD) design was also evaluated. The biological characterization of the aerogel scaffolds was also carried out regarding cell viability, adhesion and migration capacity. The obtained alginate-HA aerogel scaffolds were highly porous, biocompatible, with high fidelity to the CAD-pattern and also allowed the attachment and proliferation of mesenchymal stem cells (MSCs). An enhancement of the fibroblast migration toward the damaged area was observed in the presence of the aerogel formulations tested, which is positive in terms of bone regeneration.

This study aimed to synthesize a star-shaped micelle using 3-azido-2,2-bis(azidomethyl)propan-1-ol (pentaerythritol triazide) core, as an initiator for the synthesis of three-arm polylactic acid (PLA) block. Then, the ends of the PLA arms were converted to PLA triazide followed by conjugation to the three alkyne-PEG-maleamide through click reaction. The maleamide ends were available for coupling with sulfhydryl-modified DNA aptamer against epithelial cell adhesion molecule in order to offer targeted delivery of encapsulated drug, camptothecin to the site of action. The successful synthesis of the star-shaped polymers was confirmed via ¹HNMR. Hydrophobic anti-cancer drug, camptothecin was encapsulated into the micelles core implementing solvent switching method providing loading content (LC%) and encapsulation efficiency (EE%) of 3.7 ± 0.4 and 73.7 ± 8.2, respectively. The size of both non-targeted and aptamer-targeted micelles was determined to be 154 and 192 nm, respectively with polydispersity index below 0.3. In vitro drug release evaluation at 37 °C, pH 7.4 showed a controlled release pattern for camptothecin during 72 h. In vitro cytotoxicity of the prepared non-targeted and targeted micelles was carried out on human colorectal adenocarcinoma (HT29) and mouse colon carcinoma (C26) as EpCAM positive cell lines and Chinese hamster ovary (CHO) as EpCAM negative cell line. The results verified significantly higher cytotoxicity of the targeted micelles on HT29 and C26 cell lines, while no obvious difference was observed between targeted and non-targeted formulation on CHO cell line. The in vivo therapeutic efficiency investigation on BALB/c C26 tumor-bearing mice showed superior capability of the targeted formulation on tumor suppression and survival rate of the treated mice. The developed platform exhibited excellent characteristics to diminish camptothecin drawbacks and its adverse effects while considerably increasing its therapeutic index.