The Application Of Composite Scaffolds Based On Environmental Responsive Materials In Orthopaedic Basic Research

The damages of the musculoskeletal are very complicated, and followed by repairing and regeneration processed. The cartilage tissue is hard to regeneration dues to the inherent properties its prossessed compared to the bone tissues. And the lesion of articular cartilage may cause the entire joint regresses, which appeals for operation intervenes finally. Same as the cartilage tissue, another complicated problem the orthopedist faced is the unsatified healing of soft tisssues around the injures. Adhesion happens usually especially in the joint involved injures, and the joint function can be seriously interapted. To reach a satisfied prognosis, reoperation of construction releasing is needed.To solve these twe sticky problems, decades of researches have been applied, and the progresses have been made. But the optimal stratages are still being seeking before them are applied in human beings. Specificly, how to efficiently regenerate the cartilage tissues and prevent the adhesion before it happens have attracts the researchers’ attentions. The occurs of tissue engineering provides an option for these complicated problems. The tissue engineering technices are untilizing scaffolds encapsuled cells or drugs for the regeneration of tissues or other purpose. And accompined with the progress of material technology, how to efficiently solve the damages and complications in musculoskeletal is the main research direction of this paper. The environmentally responsive materials can react according to the surrounding micro-environments, which can further promote the efficiencies of tissue engineering application in the tissues regenenration and other functions.This study was focuses on these two sticky problems and tried to solve them more precisely and efficiently. This research included two parts as follows:First, the thermogel was untilzed as scaffold encapsuled kertogenin and BMSCs to regenerate damaged cartilage tissues.In this part, poly(L-lactide-co-glycolide)-poly(ethylene glycol)- poly(L-lactide-coglycolide)(PLGA-PEG-PLGA) thermogel was fabricated, it possess good compatibility and biodegradability. Besides, it can conveniently encapsule kertigenin and BMSCs in the solution status under the critical gelling temperature. KGN as a no-protein small moleculer was demonstrated can efficiently induces the BMSCs differentiated into chondrocytes as the transforming growth factor(TGF-β) does. And it accompanied with BMSCs as the cell source loaded into thermogel can reach a better cartilage tissue regeneration. The results of this study fund that the KGN and BMSCs both loaded thermogel implanted group showed better gross appearance, histological property, more abundant extracellular cartilage matrix and stronger mechanical property. The more COL II and GAGs expression of the KGN and BMSCs both loaded thermogel group was showed compared to other groups. All this results indicated that the composite scaffolds based on thermogel loaded KGN and BMSCs can serve as an option for cartilage regeneration.Second, we fabricated an intelligent oxidation sensitive degradation electrospinning membranes(EMs), and utilized it as physical barrier and drugs delivery vehicle loading of curcumin and celecoxib to prevent peritendinous adhesion.Peritendinous adhesion, secondary to the repair surgery of tendon rupture or injury is one of the most common causes of reoperation. The inflammentions in Achilles rupture can cause the excess production of reactive oxygen species(ROS), which inducing oxidation stress formation. Thioethers are inherently hydrophobic but can be easily oxidized to electron-withdrawing sulfone or sulfoxide and become strongly hydrophilic. The enhanced hydrophily allows stranger solvent swelling effect to increase the degradation behavior of the thioether based biomaterials, like hydroxyl rich polyesters. In this study The poly(hexanediol-diacrylate-co-ethanedithiol) EMs(PEM) were expected can release drugs according to the oxidation degree of the local microenvironment induced by local site inflammation. 1HMRI and Fourier-transform infrared spectrum(FT-IR) showed the characteristic peak of sulfone or sulfoxide. And the GPC showed the rupture of highly polymerized molecular chain of PEM. The drugs in composite EMs of oxidation sensitive materials with curcumin and celecoxib were well controlled, about 80% drugs were relaeased in about 20 days. The animal study showed that even the single curcumin or celecoxib loaded EMs exhibited adhesion preventing ability compared to control group and unloaded EMs treatment group. And the two drugs loaded EM possess the best anti-adhesion capacity, which demonstrated the curcumin and celecoxib can synergistically prevent the peritendinous adhesion, and the composite EMs could react according to the local oxidation degree. To block peritendinous adhesion these intelligent composite EMs can be utilized as novel barriers.