Rapamycin microparticles induce autophagy, prevent senescence and are effective in treatment of Osteoarthritis

Trauma to the knee joint is associated with significant cartilage degeneration and erosion of subchondral bone, which eventually leads to osteoarthritis (OA), resulting in substantial morbidity and healthcare burden. With no disease-modifying drugs in clinics, the current standard of care focuses on symptomatic relief and viscosupplementation. Modulation of autophagy and targeting senescence pathways are emerging as potential treatment strategies. Rapamycin has shown promise in OA disease amelioration by autophagy upregulation, yet its clinical use is hindered by difficulties in achieving therapeutic concentrations, necessitating multiple weekly injections. Here, we have synthesized rapamycin - loaded poly (lactic-co-glycolic acid) microparticles (RMPs) that induced autophagy, prevented senescence and sustained sulphated glycosaminoglycans(sGAG) production in primary human articular chondrocytes from OA patients. RMPs were potent, nontoxic, and exhibited high retention time (up to 35 days) in mice joints. Intra-articular delivery of RMPs effectively mitigated cartilage damage and inflammation in surgery-induced OA when administered as a prophylactic or therapeutic regimen. Together, our studies demonstrate the feasibility of using RMPs as a potential clinically translatable therapy to prevent and treat post-traumatic osteoarthritis.

Optimization of Decellularization Procedure in Rat Esophagus for Possible Development of a Tissue Engineered Construct

Background: Current esophageal treatment is associated with significant morbidity. The gold standard therapeutic strategies are stomach interposition or autografts derived from the jejunum and colon. However, severe adverse reactions, such as esophageal leakage, stenosis and infection, accompany the above treatments, which, most times, are life threating. The aim of this study was the optimization of a decellularization protocol in order to develop a proper esophageal tissue engineered construct. Methods: Rat esophagi were obtained from animals and were decellularized. The decellularization process involved the use of 3-[(3-cholamidopropyl) dimethylammonio]-1-propanesulfonate (CHAPS) and sodium dodecyl sulfate (SDS) buffers for 6 h each, followed by incubation in a serum medium. The whole process involved two decellularization cycles. Then, a histological analysis was performed. In addition, the amounts of collagen, sulphated glycosaminoglycans and DNA content were quantified. Results: The histological analysis revealed that only the first decellularization cycle was enough to produce a cellular and nuclei free esophageal scaffold with a proper extracellular matrix orientation. These results were further confirmed by biochemical quantification. Conclusions: Based on the above results, the current decellularization protocol can be applied successfully in order to produce an esophageal tissue engineered construct.

New bioreactor vessel for tissue engineering of human nasal septal chondrocytes

Cultivation of human nasal septal chondrocytes in a self-established automated bioreactor system with a new designed reactor glass vessel and the results of a computational fluid dynamics model are presented. The first results show the effect of a homogeneous fluidic condition of the continuous medium flow and the resulting stresses on the scaffolds’ surface and their influence on the migration of the cells into the scaffold matrix under these conditions. For this purpose computational models, generated with the computational fluid dynamics software STAR-CCM+, and the results of alcian blue staining for newly synthesized sulphated glycosaminoglycans have been compared during cultivation in the new and a first version of the glass reactor vessel with inhomogeneous fluidic conditions, with the same automated bioreactor system and under similar cultivation conditions.

Socket Preservation Procedure after Tooth Extraction

Jaw deformities from tooth removal can be prevented and repaired by a procedure called socket preservation. Socket preservation can greatly improve the smile’s appearance and increase the chances for successful dental implants for years to come. The procedure begins with atraumatic tooth extraction. Every attempt is made to preserve the surrounding bone and soft tissue, with an emphasis on being careful not to fracture the delicate buccal plate. There are a number of techniques and instruments that aid in this process. In general, one never wants to elevate so that force is directed toward the buccal plate. Once the tooth is extracted, all the granulation tissue is removed from the socket. It is important that good bleeding is established in the socket. Next, a bone graft material is placed into the socket.Various materials are used in modern dental and maxillofacial surgery for bone tissue substitution and reconstruction. All osteoplastic materials can be divided into four groups by origin: autogenic, allogenic, xenogenic and synthetic. The development of new medical technologies enables use of achievements in material science, biochemistry, molecular biology and genetic engineering while creating new combined synthetic materials for bone grafting. Mineralized cancellous bone is appropriate for most socket preservation cases.Synthetic resorbable materials were intended as an inexpensive substitute for natural hydroxyapatite. Synthetic graft materials include various types of calcium phosphate ceramics: tribasic calcium phosphate; bioglass; hydroxyapatite and its compositions with collagen, sulphated glycosaminoglycans such as keratan and chrondroitin sulphate as well as with sulphate and calcium phosphate.After the graft material is placed in the socket, it is then covered with a resorbable or non-resorbable membrane and sutured. Primary flap closure is not ideal. Most importantly, socket preservation helps to maintain the alveolar architecture. Socket preservation significantly reduces the loss of ridge width and height following tooth removal.