One of major challenges in the drug delivery lies in the development of nanoparticles that are effectively delivered to targeted cells and release their payload over an extended period to achieve a clinical response. In this paper, we report a new family of biocompatible and biodegradable polymer, termed polyoxalate that degrades hydrolytically into nontoxic byproducts. Polyoxalate was synthesized from a simple one-step polymerization reaction of 1,4-cyclohexanedimethanol and oxalyl chloride and had a MW of approximately 11000 Da. This polymer was designed to degrade by water hydrolysis into 1,4-cyclohexanedimethanol and oxalic acid, which can be easily removed from a body. Polyoxalate had a hydrophobic backbone and was formulated into nanoparticles with a mean diameter of 600 nm, which is suitable for drug delivery involving phagocytosis by macrophages. Polyoxalate nanoparticles were readily taken up by RAW 264.7 macrophage cells and HEK (human embryonic kidney) 293 cells and exhibited a minimal cytotoxicity in a time- and dose-dependent manner. In comparison with PLGA nanoparticles, polyoxalate nanoparticles had a significantly higher cell viability. We anticipated that the ease of synthesis and excellent biocompatibility make polyoxalate highly potent for numerous applications in drug delivery.
The present study was conducted to evaluate the force distribution in knee joint during daily activities after open-wedge high tibial osteotomy (OWHTO). A three-dimensional proximal tibial finite element model (FEM) was created using Mimics software to evaluate computed tomography (CT) scans of the tibia after OWHTO. The anterior and posterior gaps were 7.0 and 12.1 mm, respectively, and the target opening angle was 12 degrees. The loading ratio of the medial and lateral tibial plateaus was 6:4. To evaluate force distribution in the knee joint during activities of daily living (ADLs) after OWHTO, peak von Mises stresses (PVMSs) were analyzed at the plate and posterolateral edge region of osteotomized tibia. ADLs associated with greater knee flexion (sitting 90 degrees, standing 90 degrees, bending 90 degrees, stepping up stairs 60 degrees, and stepping downstairs 30 and 60 degrees) yielded PVMSs ranging from 195.2 to 221.5 MPa at the posterolateral edge region. In particular, stepping downstairs with knee flexion to 60 degrees produced the highest PVMS (221.5 MPa), greater than the yield strength (100–200 MPa). The highest plate PVMS was greater than 300 MPa during ADLs associated with flexion angles of approximately 90 degrees. However, these values did not exceed the yield stress (760.0 MPa). Conclusively, higher force was generated during higher flexion associated with weight-bearing and stepping downstairs produced a high force (even at lower flexion) on the posterolateral area of the tibial plateau. Therefore, a caution should be exercised when engaging in knee flexion of approximately 90 degrees and stepping downstairs in the early postoperative period when patients follow a weight-bearing rehabilitation protocol. However, this study is based on modeling; further translational studies are needed prior to clinical application.
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