A Simple and Efficient Method to Improve Mechanical Properties of Collagen Scaffolds by UV Irradiation

Collagen is the major protein component of cartilage, bone, skin and connective tissue and constitutes the major part of the extracellular matrix. Collagen type I has complex structural hierarchy, which consists of treepolypeptide α-chains wound together in a rod-like helical structure. Collagen is an important biomaterial, finding many applications in the field of tissue engineering. It has been processed into various shapes, such as, gel, film, sponge and fiber. It is commonly used as the scaffolding material for tissue engineering due to its many superior properties including low antigenicity and high growth promotion. Unfortunately, poor mechanical properties and rapid degradation rates of collagen scaffolds can cause instability and difficulty in handling. By crosslinking, the structural stability of the collagen and its rate of resorption can be adapted with respect to its demanding requirements. The strength, resorption rate, and biocompatibility of collagenous biomaterials are profoundly influenced by the method and extent of crosslinking. In thisstudy, the effect of UV irradiation on collagen scaffolds has been carried out.Collagen scaffolds were fabricated using freeze drying method with freezing temperature of -80oC, then exposed to UV irradiation. Mean pore size of the scaffolds was obtained as 98.52±14.51 μm using scanning electron microscopy. Collagen scaffolds exposed to UV Irradiation (254 nm) for 15 min showed the highest tensile strain (17.37±0.98 %), modulus (1.67±0.15 MPa) and maximum load (24.47±2.38 cN) values. As partial loss of the native collagen structure may influence attachment, migration, and proliferation of cells on collagen scaffolds, we detected no intact α-chains after SDS-Page chromatography. We demonstrate that UV irradiation is a rapid and easily controlled means of increasing the mechanical strength of collagen scaffolds without any molecular fracture

Behaviour of Human Induced Pluripotent Stem Cell-Derived Neural Progenitors on Collagen Scaffolds Varied in Freezing Temperature and Laminin Concentration Citation: Seeding hiPSC-NPs on Collagen Scaffolds

Abstract Objective: Biomaterial technology, when combined with emerging human induced pluripotent stem cell (hiPSC) technology, provides a promising strategy for patient-specific tissue engineering. In this study, we have evaluated the physical effects of collagen scaffolds fabricated at various freezing temperatures on the behavior of hiPSC-derived neural progenitors (hiPSC-NPs). In addition, the coating of scaffolds using different concentrations of laminin was examined on the cells. Materials and Methods: Initially, in this experimental study, the collagen scaffolds fabricated from different collagen concentrations and freezing temperatures were characterized by determining the pore size, porosity, swelling ratio, and mechanical properties. Effects of cross-linking on free amine groups, volume shrinkage and mass retention was also assessed. Then, hiPSC-NPs were seeded onto the most stable three-dimensional collagen scaffolds and we evaluated the effect of pore structure. Additionally, the different concentrations of laminin coating of the scaffolds on hiPSC-NPs behavior were assessed. Results: Scanning electron micrographs of the scaffolds showed a pore diameter in the range of 23-232 μm for the scaffolds prepared with different fabrication parameters. Also porosity of all scaffolds was >98% with more than 94% swelling ratio. hiPSC-NPs were subsequently seeded onto the scaffolds that were made by different freezing temperatures in order to assess for physical effects of the scaffolds. We observed similar proliferation, but more cell infiltration in scaffolds prepared at lower freezing temperatures. The laminin coating of the scaffolds improved NPs proliferation and infiltration in a dose-dependent manner. Immunofluorescence staining and scanning electron microscopy confirmed the compatibility of undifferentiated and differentiated hiPSC-NPs on these scaffolds. Conclusion: The results have suggested that the pore structure and laminin coating of collagen scaffolds significantly impact cell behavior. These biocompatible three-dimensional laminin-coated collagen scaffolds are good candidates for future hiPSC-NPs biomedical nerve tissue engineering applications

Exosome-inspired targeting of cancer cells with enhanced affinity

One of the major challenges in the area of novel drug delivery systems (NDDSs) is finding distinguished ligands for specific receptors represented by many cancer cells in order to enhance their cancer homing efficacy. Exosomes, the so-called natural nanocarriers or "Trojan horses,'' are secreted by the majority of cancer cells. These carriers exchange biomolecular information (e.g. proteins, siRNA, enzymes) between cancer cells and their stromal compartments in order to adjust a variety of cellular behaviours, including metastasis, apoptosis in T cells and angiogenesis. By exhibiting exosomal smart functions and biomimetic traits, exosome-mimicking nanocarriers will be one step ahead of the conventional targeted DDSs for the efficient delivery of antitumor drugs. In the present study, we tried to describe an engineering route to make some surface-functionalized nanoparticles that can mimic the targeting mechanism recruited by tumor-derived exosomes. The ligand-receptor interactions were investigated by molecular dynamics (MD) simulations. In addition, the selected ligand was experimentally studied to verify its improved targeting efficacy. The present study describes a novel targeting method that forces the mucin-domain-containing molecule-4 (TIM4)-embellished nanoparticles (NPs) to swarm towards the cancerous cells. These NPs can interact with the phosphatidylserine (PS) receptor on the surface of several kinds of cancer cells, such as U-87 MG (glioblastoma cell line). The molecular affinity between TIM4 as a homing device and PS, the target receptor, was investigated using MD simulations and surface plasmon resonance (SPR). According to the calculated free energies and the cellular uptake of TIM4-functionalized NPs, it seems that the TIM4/PS complex releases enough free energy to induce endocytosis. Our results emphasize on the potential of the proposed ligand as a good candidate for many targeted drug delivery applications. In this report, we present our proof-of-concept results in order to spotlight the importance of using computer-based simulating methods at the molecular level for the next-generation nanomedicine