Shape memory injectable cryogel based on carboxymethyl chitosan/gelatin for minimally invasive tissue engineering: In vitro and in vivo assays.

Shape-memory cryogels have drawn attention as an injectable system to minimize the risks associated with surgical implantation in tissue engineering. To achieve shape memory behavior with hydration as an external stimulus, it is necessary to have a porous elastic network. To achieve this, it is crucial to control the crosslinking process at the time of pore formation, especially for natural-based polymers. In this study, a versatile method using a cryogelation method in the presence of chemical and physical crosslinkers is investigated to obtain an injectable super macroporous elastic structure based on a poly(ampholyte) (carboxymethyl chitosan) and a protein (gelatin). Mechanical, swelling, shape memorizing behavior, injectability, and in vitro and in vivo behavior of cryogels were studied. Cryogelation in a subzero temperature led to the formation of scaffolds with interconnected pores of the size of 350 µm which swelled completely after 3 min. Cryogels had crosslink density up to 22% and elastic modulus in the hydrated state up to 0.054 and 1.733 MPa at low and high strains, respectively, and low hysteresis (<30 kPa). Injectability studies confirmed the ability of the cryogels to be injected through a 16G needle. In vitro studies demonstrated good cellular penetration, cell adhesion, and high cell viability (>100%). In vivo studies using mice showed that the body's response was befitting without inflammation and any side effect for the liver and kidneys.

Injectable hydrogels for bone and cartilage tissue engineering: a review.

Tissue engineering, using a combination of living cells, bioactive molecules, and three-dimensional porous scaffolds, is a promising alternative to traditional treatments such as the use of autografts and allografts for bone and cartilage tissue regeneration. Scaffolds, in this combination, can be applied either through surgery by implantation of cell-seeded pre-fabricated scaffolds, or through injection of a solidifying precursor and cell mixture, or as an injectable cell-seeded pre-fabricated scaffold. In situ forming and pre-fabricated injectable scaffolds can be injected directly into the defect site with complex shape and critical size in a minimally invasive manner. Proper and homogeneous distribution of cells, biological factors, and molecular signals in these injectable scaffolds is another advantage over pre-fabricated scaffolds. Due to the importance of injectable scaffolds in tissue engineering, here different types of injectable scaffolds, their design challenges, and applications in bone and cartilage tissue regeneration are reviewed.

Fe3O4 nanoparticles coated with carboxymethyl chitosan containing curcumin in combination with hyperthermia induced apoptosis in breast cancer cells.

Many studies have demonstrated that curcumin has potential anticancer properties. This research aims to study the effect of iron (II, III) oxide (Fe3O4) nanoparticles coated with carboxymethyl chitosan containing curcumin combination with hyperthermia on breast cancer cells. Magnetic nanoparticles coated with carboxymethyl chitosan containing curcumin (MNP-CMC-CUR) were prepared and specified. MCF-7, MDA-MB-231, and human fibroblast cells were treated with free curcumin and MNP-CMC-CUR at concentrations of 0-60 µM and at different time points. A combined therapy of MNP-CMC-CUR and hyperthermia was performed on MCF-7 cells. The cytotoxicity of curcumin and MNP-CMC-CUR combined with hyperthermia was assessed by MTT. The changes in TP53 and CASPASE3 gene expression were evaluated using real-time PCR. Both cell apoptosis and cell cycle were studied by Annexin/PI staining. The results of MTT showed that the IC50 amount of MNP-CMC-CUR has significantly decreased compared to free curcumin (p < 0.05) and MNP-CMC-CUR in combination with the hyperthermia, and significantly reducing the metabolic activity of the cells (p < 0.05). Real-time PCR results revealed the up-regulation of TP53 and CASPASE3 (p < 0.05). The combinational therapy-induced cell apoptosis (64.51%) and sub-G1 cell cycle were arrested in MCF-7 cells. Based on these observations, a combination of MNP-CMC-CUR with hyperthermia could inhibit the proliferation of MCF-7 cells.

Fabrication of nanocomposite/nanofibrous functionally graded biomimetic scaffolds for osteochondral tissue regeneration.

One of the main challenges in treating osteochondral lesions via tissue engineering approach is providing scaffolds with unique characteristics to mimic the complexity. It has led to application of heterogeneous scaffolds as a potential candidate for engineering of osteochondral tissues, in which graded multilayered-structure should promote bone and cartilage growth. By designing three-dimensional (3D)-nanofibrous scaffolds mimicking the native extracellular matrix's nanoscale structure, cells can grow in controlled conditions and regenerate the damaged tissue. In this study, novel 3D-functionality graded nanofibrous scaffolds composed of five layers based on different compositions containing polycaprolactone(PCL)/gelatin(Gel)/nanohydroxyapatite (nHA) for osteoregeneration and chitosan(Cs)/polyvinylalcohol(PVA) for chondral regeneration are introduced. This scaffold is fabricated by electrospinning technique using spring as collector to create 3D-nanofibrous scaffolds. Fourier-transform infrared spectroscopy, X-ray diffraction, energy dispersive X-ray spectroscopy, scanning electron microscopy, mechanical compression test, porosimetry, and water uptake studies were applied to study each layer's physicochemical properties and whole functionally graded scaffold. Besides, biodegradation and biological studies were done to investigate biological performance of scaffold. Results showed that each layer has a fibrous structure with continuous nanofibers with improved pore size and porosity of novel 3D scaffold (6-13 µm and 90%) compared with two-dimensional (2D) mat (2.2 µm and 19.3%) with higher water uptake capacity (about 100 times of 2D mat). Compression modulus of electrospun scaffold was increased to 78 MPa by adding nHA. The biological studies revealed that the layer designed for osteoregeneration could improve cell proliferation rate in comparison to the layer designed for chondral regeneration. These results showed such structure possesses a promising potential for the treatment of osteochondral defects.