ABSTRACT
Due to good mechanical properties and biocompatibility, tissue engineering scaffolds have become the vital method for repairing and regenerating articular cartilage defects. With the continuous development of tissue engineering technology, many scaffolds preparation and formation methods have been developed and tested in the past decade, however, the preparation of ideal regenerative scaffolds remain controversial. As load-bearing tissue inside the body joints, the matrix structure and cell composition of articular cartilage are hierarchical, and there are several smooth natural gradients from the cartilage surface to the subchondral bone layer, including cell phenotype and number, specific growth factors, matrix composition, fiber arrangement, mechanical properties, nutrient and oxygen consumption. Therefore, in the design of regenerative scaffolds, it is necessary to achieve these gradients to regenerate articular cartilage in situ. In recent studies, many new biomimetic gradient scaffolds have been used to simulate the natural gradient of articular cartilage. These scaffolds show different mechanical, physicochemical or biological gradients in the structure, and have achieved good repair effects. The related articles on tissue engineering for the treatment of articular cartilage defects were retrieved by searching databases with key wordsarticular cartilage injury, cartilage repair and gradient scaffolds. In this work,the structural, biochemical, biomechanical and nutrient metabolism gradients of natural articular cartilage were studied and summarized firstly. Then, the latest design and construction of articular cartilage gradient scaffolds were classified. Besides that, the material composition (such as hydrogels, nanomaterials, etc.) and the preparation process (such as electrospinning, 3D printing, etc.) of grandient scaffolds were further enhanced. Finally, the prospect and challenge of biomimetic gradient scaffolds in cartilage engineering are discussed, which provides a theoretical basis for the successful application of gradient scaffolds in clinical transformation.
ABSTRACT
The treatment of articular cartilage (AC) injury caused by various reasons is still a major clinical problem. The emergence of cartilage tissue engineering brings new hope for the treatment of AC injury. In general, AC tissue engineering can be divided into two categories, including cell-based tissue engineering and cell-free tissue engineering. Although cell-based tissue engineering can repair cartilage damage to a certain extent, existing therapeutic strategies still suffer from limited cell sources, high costs, risk of disease transmission, and complex procedures. However, the cell-free tissue engineering avoids these shortcomings and brings hope for in-situ AC regeneration. Non-cellular tissue engineering is mainly used to recruit endogenous stem cells/progenitor cells (SCPCs) to reach the site of cartilage injury, and provide a suitable regenerative microenvironment to promote cell proliferation and chondrogenic differentiation, then the maturation of new cartilage tissue was promoted. Therefore, it is also called as cell-homing in situ tissue engineering. Successful recruitment of endogenous SCPCs is the first step in in-situ cartilage tissue engineering. This review aims to introduce chemokine response of cartilage injury, systematically summarize traditional chemoattractant (chemokines and growth factors etc.) and emerging chemoattractant (functional peptides, exosomes and nucleic acid adapters etc.), evaluate the combination mode between chemoattractant and delivery devices, discuss the prospects and challenges of chemoattractant-mediated in situ tissue engineering and provide theoretical basis for the design of endogenous SCPCs homing-based in situ tissue engineering.
ABSTRACT
Phospho-histone H2AX(γH2AX) has been widely used in vitro genotoxicity evaluation of ionizing radiation, carcinogenic substances and cigarette smoke as an important biomarker of DNA double stranded breaks ( DSBs) . The study developed an enzyme-linked immunesorbent assay for detection of the content ofγH2AX in cells to evaluate the genotoxicity of cigarette smoke. The study exposed CHO cells with cigarette smoke total particulate matter ( TPM) and cigarette smoke condensate ( CSC) of different dose, dose-effect relationship between smoke exposure and DNA damage and the poisonous difference of cigarette smoke components has been investigated by detecting the content change ofγH2 AX in cells under different exposure time and dose. In addition, reactive oxygen species ( ROS) in cells were also detected to study the mechanism of cigarette smoke exposure induced DSBs. The experiment result showed that the required time for the level ofγH2AX in cells grew to the peak prolonged with increased exposure dose. Once the level of γH2AX in cells grew to the peak value, then it decreased slowly; the level of γH2AX in cells rised with increasing dose of cigarette smoke;The effect of TPM on the content change of γH2AX was more than CSC; Moreover, smoke exposure could induce concentration increase of ROS in cells, and a good correlation of content change of ROS and γH2AX in cells were found, free radicals in cigarette smoke may be one major cause of DSBs.