=====Sustained-Release Hydrogel-Based Rhynchophylline Delivery System Improved Injured Tendon Repair===== ====Abstract==== ====Commentary==== What is Rhy? * Uncaria (A TCM drug)'s active ingredient is Rhynchophylline (Rhy) * Rhy inhibits intra-abdominal adhesion formation. * But Rhy has short half-life (? duration) --> need sustained release mechanism --> biodegradable hydrogel * Rhy also crosses BBB What is the carrier used? * Thiol-modified HA * Rhy solution embedded in hydrogel using cross=linking with HA-SH and PEG-DA * material/structural strength * release characteristics in vitro with PBS/ ddH20 - different; slower in PBS -- 60 in 21 days Product testing? * not stated where Rhy is from? * cytotoxicity: MTT * release In vitro model? * chicken flexor tenocytes * cell cycle analysis * cell apoptosis * transcriptome sequencing * Western blot * analysis for expression of genes What tendon model is used? * Adult Sanhuang chickens 1.5 kg * bilateral long toes * modified Kessler repair * randomized to control, 200 uL HG, 200 HG/ 200 ng Rhy, 200/400, 200/800 * outcomes * gliding excursion * adhesion score * ultimate strength * Histo: HE, MMP2 IHC --> ImageJ (particles) How was it assessed? All toes were harvested at weeks 6. Before scoring adhesions, gliding excursion testing was detected with a tensile testing machine (Model 4411; Instron Corp., Canton, MA, USA). Briefly, operated toes were transfixed with K-wires on measurement board. FDP tendon was exposed by an incision from the knee joint to the ankle joint level and connected to the upper clamp, while the measurement board was connected to the lower clamp. The proximal end of the FDP tendon was pulled at a constant speed of 25 mm/min until the force reach 15 N. Testing software (Series IX software; Instron Corp.) measured the load and gliding displacement of the FDP tendons simultaneously. The load-displacement curve was generated automatically by computer. Adhesion formed around the injured site of tendons was evaluated and scored by an established grading method. The repaired tendons were split out slightly along the entire length of the toes. Then the morphology and appearance of the adhesion, such as the severity and extent, could be observed. Three people blinded to the experiment evaluated the adhesion scores and the mean values were finally recorded. The healing FDP tendons were then separated slightly from surrounding tissues and removed completely through their entire length to test the healing strength by an Instron testing machine (model 4411; Instron Inc., Norwood, MA, USA). Two ends of the FDP tendon were nipped in the lower clamp and upper clamp respectively, while the repair site was maintained in the middle of two clamps. Be sure the clamps were reset without any load. Then the upper clamp carried one end of the FDP tendon pulled up with the constant speed of 25 mm/min, and stopped when the FDP tendon ruptured. The load-displacement curve recorded by a testing software program (Series IX; Instron) indicating a sharp decline represented the rupture of the repair. Strengths & Weakness * quite comprehensive, from in-vitro to in-vivo * tendon assessment not so clear: * adhesion scoring system not stated * UTS for rupture ====See also==== * [[md:flexor_tendon|Flexor Tendon Healing]] * [[md:flexor_tendon_adhesions|Flexor Tendon Adhesions]] ====Source===== Yang, Qian Qian, Luzhong Zhang, Fei Ju, and You Lang Zhou. “Sustained-Release Hydrogel-Based Rhynchophylline Delivery System Improved Injured Tendon Repair.” Colloids and Surfaces B: Biointerfaces, May 2021, 111876. https://doi.org/10.1016/j.colsurfb.2021.111876. ====History==== * created 2021-06-01