Osteochondral Interface: Regenerative Engineering and Challenges.

Osteochondral (OC) defects are debilitating for patients and represent a significant clinical problem for orthopedic surgeons as well as regenerative engineers due to their potential complications, which are likely to lead to osteoarthritis and related diseases. If they remain untreated or are treated suboptimally, OC lesions are known to impact the articular cartilage and the transition from cartilage to bone, that is, the cartilage-bone interface. An important component of the OC interface, that is, a selectively permeable membrane, the tidemark, still remains unaddressed in more than 90% of the published research in the past decade. This review focuses on the structure, composition, and function of the OC interface, regenerative engineering attempts with different scaffolding strategies and challenges ahead of us in recapitulating the native OC interface. There are different schools of thought regarding the structure of the native OC interface: stratified and graded. The former assumes the cartilage-to-bone interface to be hierarchically divided into distinct yet continuous zones of uncalcified cartilage-calcified cartilage-subchondral bone. The latter assumes the interface is continuously graded, that is, formed by an infinite number of layers. The cellular composition of the interface, either in respective layers or continuously changing in a graded manner, is chondrocytes, hypertrophic chondrocytes, and osteoblasts as moved from cartilage to bone. Functionally, the interface is assumed to play a role in enabling a smooth transition of loads exerted on the cartilage surface to the bone underneath. Regenerative engineering involves, first, a characterization of the native OC interface in terms of the composition, structure, and function, and, then, proposes the appropriate biomaterials, cells, and biomolecules either alone or in combination to eventually form a structure that mimics and functionally behaves similar to the native interface. The major challenge regarding regeneration of the OC interface appears to lie, in addition to others, in the formation of tidemark, which is a thin membrane separating the OC interface into two distinct zones: the avascular OC interface and the vascular OC interface. There is a significant amount of literature on regenerative approaches to the OC interface; however, only a small portion of them consider the importance of tidemark. Therefore, this review aims at highlighting the significance of the structural organization of the components of the OC interface and increasing the awareness of the orthopedics community regarding the importance of tidemark formation after clinical interventions or regenerative engineering attempts.

A high scale SARS-CoV-2 profiling by its whole-genome sequencing using Oxford Nanopore Technology in Kazakhstan.

Severe acute respiratory syndrome (SARS-CoV-2) is responsible for the worldwide pandemic, COVID-19. The original viral whole-genome was sequenced by a high-throughput sequencing approach from the samples obtained from Wuhan, China. Real-time gene sequencing is the main parameter to manage viral outbreaks because it expands our understanding of virus proliferation, spread, and evolution. Whole-genome sequencing is critical for SARS-CoV-2 variant surveillance, the development of new vaccines and boosters, and the representation of epidemiological situations in the country. A significant increase in the number of COVID-19 cases confirmed in August 2021 in Kazakhstan facilitated a need to establish an effective and proficient system for further study of SARS-CoV-2 genetic variants and the development of future Kazakhstan's genomic surveillance program. The SARS-CoV-2 whole-genome was sequenced according to SARS-CoV-2 ARTIC protocol (EXP-MRT001) by Oxford Nanopore Technologies at the National Laboratory Astana, Kazakhstan to track viral variants circulating in the country. The 500 samples kindly provided by the Republican Diagnostic Center (UMC-NU) and private laboratory KDL "Olymp" were collected from individuals in Nur-Sultan city diagnosed with COVID-19 from August 2021 to May 2022 using real-time reverse transcription-quantitative polymerase chain reaction (RT-qPCR). All samples had a cycle threshold (Ct) value below 20 with an average Ct value of 17.03. The overall average value of sequencing depth coverage for samples is 244X. 341 whole-genome sequences that passed quality control were deposited in the Global initiative on sharing all influenza data (GISAID). The BA.1.1 (n = 189), BA.1 (n = 15), BA.2 (n = 3), BA.1.15 (n = 1), BA.1.17.2 (n = 1) omicron lineages, AY.122 (n = 119), B.1.617.2 (n = 8), AY.111 (n = 2), AY.126 (n = 1), AY.4 (n = 1) delta lineages, one sample B.1.1.7 (n = 1) belongs to alpha lineage, and one sample B.1.637 (n = 1) belongs to small sublineage were detected in this study. This is the first study of SARS-CoV-2 whole-genome sequencing by the ONT approach in Kazakhstan, which can be expanded for the investigation of other emerging viral or bacterial infections on the country level.