Search

Cartilage defects are one of the most common symptoms of osteoarthritis (OA), a degenerative disease that affects millions of people world-wide and places a significant socio-economic burden on society. Hydrogels, which are a class of biomaterials that are elastic, and display smooth surfaces while exhibiting high water content, are promising candidates for cartilage regeneration. In recent years, various kinds of hydrogels have been developed and applied for the repair of cartilage defects in vitro or in vivo, some of which are hopeful to enter clinical trials. In this review, recent research findings and developments of hydrogels for cartilage defects repair are summarized. We discuss the principle of cartilage regeneration, and outline the requirements that have to be fulfilled for the deployment of hydrogels for medical applications. We also highlight the development of advanced hydrogels with tailored properties for different kinds of cartilage defects to meet the requirements of cartilage tissue engineering and precision medicine., Graphical abstract Hydrogels applied in joints for the repair of cartilage defects and cartilage regeneration. Hydrogels are three-dimensional hydrophilic polymer networks that can be fabricated from synthetic polymers, polysaccharides, protein, and peptides, and can be designed as injectable or in situ forming for practical clinical application.Image 1, Highlights • The biotechnology of developing hydrogels for cartilage defects repair is promising. • The principle for cartilage regeneration using hydrogels and requirements for clinical transformation are summarized. • Advanced hydrogels with tailored properties for different kinds of cartilage defects are discussed.

Cartilage adheres to subchondral bone via a specific osteochondral interface tissue where forces are transferred from soft cartilage to hard bone without conferring fatigue damage over a lifetime of load cycles. However, the fine structure and mechanical properties of the osteochondral interface tissue remain unclear. Here, we identified an ultrathin ∼20-30 μm graded calcified region with two-layered micronano structures of osteochondral interface tissue in the human knee joint, which exhibited characteristic biomolecular compositions and complex nanocrystals assembly. Results from finite element simulations revealed that within this region, an exponential increase of modulus (3 orders of magnitude) was conducive to force transmission. Nanoscale heterogeneity in the hydroxyapatite, coupled with enrichment of elastic-responsive protein-titin, which is usually present in muscle, endowed the osteochondral tissue with excellent mechanical properties. Collectively, these results provide novel insights into the potential design for high-performance interface materials for osteochondral interface regeneration.

Stem cell therapies are unsatisfactory due to poor cell survival and engraftment. Stem cell used for therapy must be properly “tuned” for a harsh in vivo environment. Herein, we report that transfer of exogenous mitochondria (mito) to adipose‐derived mesenchymal stem cells (ADSCs) can effectively boost their energy levels, enabling efficient cell engraftment. Importantly, the entire process of exogeneous mitochondrial endocytosis is captured by high‐content live‐cell imaging. Mitochondrial transfer leads to acutely enhanced bioenergetics, with nearly 17% of higher adenosine 5′‐triphosphate (ATP) levels in ADSCs treated with high mitochondrial dosage and further results in altered secretome profiles of ADSCs. Mitochondrial transfer also induced the expression of 334 mRNAs in ADSCs, which are mainly linked to signaling pathways associated with DNA replication and cell division. We hypothesize that increase in ATP and cyclin‐dependent kinase 1 and 2 expression might be responsible for promoting enhanced proliferation, migration, and differentiation of ADSCs in vitro. More importantly, mito‐transferred ADSCs display prolonged cell survival, engraftment and horizontal transfer of exogenous mitochondria to surrounding cells in a full‐thickness skin defect rat model with improved skin repair compared with nontreated ADSCs. These results demonstrate that intracellular mitochondrial transplantation is a promising strategy to engineer stem cells for tissue regeneration.

A high number of sport injuries result in damage to articular cartilage, a tissue type with poor self-healing capacity. Articular cartilage tissue is a sophisticated hydrogel, which contains 80% wa...

The interface performance of steel fiber-reinforced concrete (SFRC) is a critical factor in determining mechanical properties and durability. The degradation of the concrete matrix and micro-structure interface is caused by environmental erosion, which shortens the service life of the structure design. Considering different volume contents of steel fiber (0%, 1%, 2%), the failure mechanism of SFRC under different environmental erosion conditions was studied through a laboratory test scheme. A total of six environmental factors are selected, including water, sodium chloride solution, sodium sulfate solution, dilute sulfuric acid solution, sodium hydroxide solution, and a freeze-thaw cycle. When subjected to different erosion concentrations and periods, micro-structure and axial bearing capacity deterioration laws are compared and analyzed. A durability equation related to fiber mixture ratio and strength is presented based on the experimental data and the numerical simulation method. The influence of different environments on steel fiber-reinforced concrete is analyzed, and the grey correlation degree of axial compressive strength is analyzed. The experimental results show that steel fiber can effectively improve the concrete axial bearing capacity, but different responses are observed under the various erosion conditions. A freeze-thaw cycle environment has the most significant impact on the axial compressive strength of concrete, followed by the sulfuric acid environment, and other environments have a weaker impact. The research results will provide a theoretical basis for predicting the performance deterioration of SFRC concerning other erosion conditions and periods.

Supplemental material, DS_10.1177_0363546519848678 for Single-Cell Profiles and Clinically Useful Properties of Human Mesenchymal Stem Cells of Adipose and Bone Marrow Origin by Wenyan Zhou, Junxin Lin, Kun Zhao, Kaixiu Jin, Qiulin He, Yejun Hu, Hongwei Ouyang, Gang Feng, Youzhi Cai, Chen Xia, Hua Liu, Weiliang Shen and Xueqing Hu in The American Journal of Sports Medicine

Large area skull defects accompanied by craniocerebral injury are life-threating diseases that are difficult to treat due to the large area of damage and intracranial hypertension. An autologous bone is an ideal source for the regeneration of bone, including skull defects. However, two-step treatment, including craniectomy and cranioplasty, is the main strategy in clinical practice to stabilize intracranial pressure, but still remains a huge obstacle in both the preservation of auto-bone fragments and protection of exposed brain tissue. In this study, an elastic auto-bone patch was developed to provide a new and one-step method for repairing large skull defects which are currently repaired with two stages of surgery. The elastic auto-bone patch is formed by bonding auto-bone fragments together using hydrogels, which is then re-implanted to bone defects to repair large skull defects. The auto-bone patch could adapt to changes in intracranial pressure to protect brain tissue for damage, integrate well with surrounding bone tissues, and promote bone regeneration. After 8 weeks implantation, the large-size skull defect is filled with new formed bone tissues in the group of treating with auto-bone patch. This study introduced a new procedure on the application of elastic auto-bone patch to repair large area skull defects.

Microsphere (MS)-based systems provides great advantages for cell expansion and transplantation due to their high surface-to-volume ratio and biomimetic environment. However, a MS-based system that includes cell attachment, proliferation, passage, harvest, cryopreservation, and tissue engineering together has not been realized yet. An "all-in-one" gel MS-based system is established for human adipose-derived mesenchymal stem cells (hADSCs), realizing real 3D culture with enhanced expansion efficiency and simplified serial cell culture operations, and construction of macrotissues with uniform cell distribution and specific function. A 3D digital light-processing technology is developed to fabricate gel MSs in an effective way. The printed MSs present a suitable environment with rough surface architecture and the mechanical properties of soft tissues, leading to high cell viability, attachment, proliferation, activity, and differentiation potential. Further, convenient standard operation procedures, including cell passage, detachment, and cryopreservation, are established for cell culture on the gel MSs. Finally, hADSCs-loaded gel MSs form macrotissues through a "bottom-up" approach, which demonstrates the potential applications for tissue engineering. These findings exhibit the feasibility and beauty of "all-in-one" stem cell culture and tissue engineering system.

In many prokaryotes but limited eukaryotic species, the combination of transposon mutagenesis and high-throughput sequencing has greatly accelerated the identification of essential genes. Here we successfully applied this technique to the methylotrophic yeast Pichia pastoris and classified its conditionally essential/non-essential gene sets. Firstly, we showed that two DNA transposons, TcBuster and Sleeping beauty, had high transposition activities in P. pastoris. By merging their insertion libraries and performing Tn-seq, we identified a total of 202,858 unique insertions under glucose supported growth condition. We then developed a machine learning method to classify the 5,040 annotated genes into putatively essential, putatively non-essential, ambig1 and ambig2 groups, and validated the accuracy of this classification model. Besides, Tn-seq was also performed under methanol supported growth condition and methanol specific essential genes were identified. The comparison of conditionally essential genes between glucose and methanol supported growth conditions helped to reveal potential novel targets involved in methanol metabolism and signaling. Our findings suggest that transposon mutagenesis and Tn-seq could be applied in the methylotrophic yeast Pichia pastoris to classify conditionally essential/non-essential gene sets. Our work also shows that determining gene essentiality under different culture conditions could help to screen for novel functional components specifically involved in methanol metabolism.