Current advances in solid free-form techniques for osteochondral tissue engineering

Osteochondral （OC） lesions are characterized by defects in two different zones, the cartilage region and subchondral bone region. These lesions are frequently associated with mechanical instability, as well as osteoarthritic degenerative changes in the knee. The lack of spontaneous healing and the drawbacks of the current treatments have increased the attention from the scientific community to this issue. Different tissue engineering approaches have been attempted using different polymers and different scaffolds＇ processing. However, the current conventional techniques do not allow the full control over scaffold fabrication, and in this type of approaches, the tuning ability is the key to success in tissue regeneration. In this sense, the researchers have placed their efforts in the development of solid free-form （SFF） techniques. These techniques allow tuning different properties at the micro-macro scale, creating scaffolds with appropriate features for OC tissue engineering. In this review, it is discussed the current SFF techniques used in OC tissue engineering and presented their promising results and current challenges.

ALK5 transfection of bone marrow mesenchymal stem cells to repair osteoarthritis of knee joint

Previous studies have suggested that the transforming growth factor-β receptor ALK5 is crucial for articular chondrogenesis by bone marrow mesenchymal stem cells. Here, the wild-type ALK5 plasmids were mutated by overlapping extended PCR and transfected into bone marrow mesenchymal stem cells. The knee joint osteoarthritis mouse model was constructed by cutting oft＂ the anterior cruciate ligament and divided into three groups： saline group, bone marrow mesenchymal stem cells and ALK5-transfected bone marrow mesenchymal stem cells group. HE staining showed that the articular cartilage lesions were more serious of saline group compared with that of mesenchymal stem cell group, and this trend was more pronounced as time goes on. Immunohistochemical staining showed that although the expression level of type II collagen in all three groups down-regulated gradually upon time, its expression in ALK5-transfected bone marrow mesenchymal stem cells group was significantly enhanced compared with the other two groups. Micro-CT also suggested that ALK5 transfection of mouse bone marrow mesenchymal stem cells would promote repairing the knee cartilage lesions with arthritis of the mice. Although the osteoarthritis mechanism underlying a variety of factors work together, and the appropriate proportion of ALKS/ALK1 was also emphasized for the treatment of osteoarthritis. This work therefore demonstrated that ALK5 transfection of bone marrow mesenchymal stem cells could be a promising stem cell therapy for repair of cartilage lesions.

Sanitary Regulation of Pharmaceutical Products in Mexico （Sanitary Registration-Board Arrangement-Patent）-Monoclonal Antibody Case Study

The Federal Commission for Protection against Health Risks in Mexico （COFEPRIS） is responsible for the regulation and health promotion of the production, commercialization, import, export, publicity or involuntary exposure of medicines and technologies for health. For its part, the Mexican Institute of Industrial Property （IMPI） is a decentralized public body with legal personality, own property and legal authority to administer the industrial property system in our country. In the year 2000, on September 19, the official journal published the linking of patents related to allopathic medicines and the sanitary registry. Objectives： To publicize the process of linking the Sanitary-Patent Registry as a case study to delimit the scope of the new pharmaceutical products. Methodology： Request the information to COFEPRIS for the registration of a new pharmaceutical product; Establish flow diagrams for the registration of： innovative products, generic products, biotech products and bio similar products; Integrate the documents in the dossier of the pharmaceutical product for sanitary registration; Elaborate sworn letter of non-invasion of patents and study of patents; Submit the Health Registry; Intergovernmental consultation. Sanitary Registry Results： Search of patents in databases to elaborate state of the art, to write letter under protest to say truth that is not invading any patent, when developing a composition of cetuximab, as generic product since the patent molecule expired in 2016 and 11 patents related to compositions, preparations and finished product preparation processes. Conclusions： COFEPRIS will determine through intergovernmental consultation with the IMPI whether or not a patent is invaded, according to the case it will grant the registration or send the corresponding prevention for cetuximab, in case that invading can also be a refusal of grant.