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Recently, interest in polyphenol-containing composite adhesives for various biomedical applications has been growing. Tannic acid (TA) is a polyphenolic compound with advantageous properties, including antioxidant and antimicrobial properties. Additionally, TA contains multiple hydroxyl groups that exhibit biological activity by forming hydrogen bonds with proteins and biomacromolecules. Furthermore, TA-containing polymer composites exhibit excellent tissue adhesion properties. In this study, the gelation behavior and adhesion forces of TA/Pluronic F127 (TA/PluF) composite hydrogels were investigated by varying the TA and PluF concentrations. PluF (above 16 wt%) alone showed temperature-responsive gelation behavior because of the closely packed micelle aggregates. After the addition of a small amount of TA, the TA/PluF hydrogels showed thermosensitive behavior similar to that of PluF hydrogels. However, the TA/PluF hydrogels containing more than 10 wt% TA completely suppressed the thermo-responsive gelation kinetics of PluF, which may have been due to the hydrogen bonds between TA and PluF. In addition, TA/PluF hydrogels with 40 wt% TA showed excellent tissue adhesion properties and bursting pressure in porcine intestinal tissues. These results are expected to aid in understanding the use of mixtures of TA and thermosensitive block copolymers to fabricate adhesive hydrogels for versatile biomedical applications.
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BACKGROUND: Although high tibial osteotomy (HTO) is an established treatment option for medial compartment osteoarthritis, predictive factors for HTO treatment success remain unclear. This study aimed to identify informative variables associated with HTO treatment success and to develop and internally validate machine learning algorithms to predict which patients will achieve HTO treatment success for medial compartmental osteoarthritis. METHODS: This study retrospectively reviewed patients who underwent medial opening-wedge HTO (MOWHTO) at our center between March 2010 and December 2015. The primary outcomes were a lack of conversion to total knee arthroplasty (TKA) and achievement of a minimal clinically important difference of improvement in the Knee Injury and Osteoarthritis Outcome Score (KOOS) at a minimum of five years postoperatively. Recursive feature selection was used to identify the combination of variables from an initial pool of 25 features that optimized model performance. Five machine learning algorithms (XGBoost, multilayer perception, support vector machine, elastic-net penalized logistic regression, and random forest) were trained using five-fold cross-validation three times and applied to an independent test set of patients. The performance of the model was evaluated by the area under the receiver operating characteristic curve (AUC). RESULTS: A total of 231 patients were included, and 200 patients (86.6%) achieved treatment success at the mean of 9 years of follow-up. A combination of seven variables optimized algorithm performance, and the following specific cutoffs increased the likelihood of MOWHTO treatment success: body mass index (BMI) ≤ 26.8 kg/m2, preoperative KOOS for pain ≤ 46.0, preoperative KOOS for quality of life ≤ 33.0, preoperative International Knee Documentation Committee score ≤ 42.0, preoperative Short-Form 36 questionnaire (SF-36) score > 42.25, three-month postoperative hip-knee-ankle angle > 1.0°, and three-month postoperative medial proximal tibial angle (MPTA) > 91.5° and ≤ 94.7°. The random forest model demonstrated the best performance (F1 score: 0.93; AUC: 0.81) and was transformed into an online application as an educational tool to demonstrate the capabilities of machine learning. CONCLUSIONS: The random forest machine learning algorithm best predicted MOWHTO treatment success. Patients with a lower BMI, poor clinical status, slight valgus overcorrection, and postoperative MPTA < 94.7 more frequently achieved a greater likelihood of treatment success. LEVEL OF EVIDENCE: Level III, retrospective cohort study.
Assuntos
Aprendizado de Máquina , Osteoartrite do Joelho , Osteotomia , Tíbia , Humanos , Masculino , Feminino , Osteotomia/métodos , Estudos Retrospectivos , Pessoa de Meia-Idade , Osteoartrite do Joelho/cirurgia , Tíbia/cirurgia , Idoso , Resultado do Tratamento , Articulação do Joelho/cirurgia , Artroplastia do Joelho/métodosRESUMO
Introduction: Cartilage regeneration is a challenging issue due to poor regenerative properties of tissues. Electrospun nanofibers hold enormous potentials for treatments of cartilage defects. However, nanofibrous materials used for the treatment of cartilage defects often require physical and/or chemical modifications to promote the adhesion, proliferation, and differentiation of cells. Thus, it is highly desirable to improve their surface properties with functionality. We aim to design hydrophilic, adhesive, and compound K-loaded nanofibers for treatments of cartilage defects. Methods: Hydrophilic and adhesive compound K-containing polycaprolactone nanofibers (CK/PCL NFs) were prepared by coatings of gallic acid-conjugated chitosan (CHI-GA). Therapeutic effects of CHI-GA/CK/PCL NFs were assessed by the expression level of genes involved in the cartilage matrix degradation, inflammatory response, and lipid accumulations in the chondrocytes. In addition, Cartilage damage was evaluated by safranin O staining and immunohistochemistry of interleukin-1ß (IL-1ß) using OA animal models. To explore the pathway associated with therapeutic effects of CHI-GA/CK/PCL NFs, cell adhesion, phalloidin staining, and the expression level of integrins and peroxisome proliferator-activated receptor (PPARs) were evaluated. Results: CHI-GA-coated side of the PCL NFs showed hydrophilic and adhesive properties, whereas the unmodified opposite side remained hydrophobic. The expression levels of genes involved in the degradation of the cartilage matrix, inflammation, and lipogenesis were decreased in CHI-GA/CK/PCL NFs owing to the release of CK. In vivo implantation of CHI-GA/CK/PCL NFs into the cartilage reduced cartilage degradation induced by destabilization of the medial meniscus (DMM) surgery. Furthermore, the accumulation of lipid deposition and expression levels of IL-1ß was reduced through the upregulation of PPAR. Conclusion: CHI-GA/CK/PCL NFs were effective in the treatments of cartilage defects by inhibiting the expression levels of genes involved in cartilage degradation, inflammation, and lipogenesis as well as reducing lipid accumulation and the expression level of IL-1ß via increasing PPAR.