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.
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.
The anti-cancer mechanisms of curcumin have been reported to include suppressions of angiogenesis and tumor proliferation. The main goal of this research is to increase the solubility of curcumin by cold atmospheric plasma (CAP) and assess the effects of modified curcumin by charging with tri-polyphosphate chitosan nanoparticles for MCF-7, MDA-MB-231 breast cancer cells, and human fibroblast cells. Curcumin modification was done by CAP and its solubility was evaluated by spectrophotometry. After loading modified curcumin into nano-chitosan-TPP, nanocurcumin was characterized by scanning electron microscopy. Cellular viability and apoptosis of treated cells were assessed by MTT and Annexin V. The changes of messenger RNA expression of TP5353 and VEGF genes were analyzed by real-time PCR. CAP was able to transform the curcumin to possess hydrophilic characteristics after 90 seconds. The mean diameter of Curcumin loaded chitosannanoparticles (NPs) were determined as 48 nm. MTT results showed that the IC 50 of nano Cur-chitosan-TPP was effectively decreased compared to free curcumin in MCF-7 (15 μg/mL at 72 hours vs 20 μg/mL at 48 hours). Additionally, nano Cur-chitosan-TPP had no significant effect on normal cells (Human dermal fibroblas: HDF), whereas it also decreased the viability of triple negative breast cancer cell line (MDA-MB-231). Realtime PCR results showed that expression level of TP53 gene was upregulated (P = .000), whereas VEGF gene downregulated (P = .000) in treated MCF-7 cells. Curcumin loaded chitosan nanoparticles have led to an induction of apoptosis (79.93%) and cell cycle arrest (at S and G2M). Modified-curcumin-tri-polyphosphate chitosan nanoparticles using CAP can be considered as a proper candidate for breast cancer treatment.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.