Ribosomal protein S3 mediates drug resistance of proteasome inhibitor: potential therapeutic application in multiple myeloma.

Multiple myeloma (MM) remains incurable due to drug resistance. Ribosomal protein S3 (RPS3) has been identified as a non-Rel subunit of NF-κB. However, the detailed biological roles of RPS3 remain unclear. Here, we report for the first time that RPS3 is necessary for MM survival and drug resistance. RPS3 was highly expressed in MM, and knockout of RPS3 in MM inhibited cell growth and induced cell apoptosis both in vitro and in vivo. Overexpression of RPS3 mediated the proteasome inhibitor resistance of MM and shortened the survival of MM tumor-bearing animals. Moreover, our present study found an interaction between RPS3 and the thyroid hormone receptor interactor 13 (TRIP13), an oncogene related to MM tumorigenesis and drug resistance. We demonstrated that the phosphorylation of RPS3 was mediated by TRIP13 via PKCδ, which played an important role in activating the canonical NF-κB signaling and inducing cell survival and drug resistance in MM. Notably, the inhibition of NF-κB signaling by the small-molecule inhibitor targeting TRIP13, DCZ0415, was capable of triggering synergistic cytotoxicity when combined with bortezomib in drug-resistant MM. This study identifies RPS3 as a novel biomarker and therapeutic target in MM.

Outcomes of laparoscopic and open ventriculoperitoneal shunt placement.

OBJECTIVE: Ventriculoperitoneal (VP) shunt placement requires a concurrent abdominal procedure. For peritoneal access laparoscopic or open approach may be utilized. Our aim was to compare patient/procedure characteristics and outcomes by peritoneal approach for VP shunts in children. METHODS: NSQIP-Pediatric procedure targeted cerebral spinal fluid shunt Participant Use Data Files from 2016 to 2020 were queried. Patients were grouped into laparoscopic vs open abdominal approach. Patient demographics, procedure characteristics and 30-day outcomes were compared. RESULTS: 7742 NSQIP-Pediatric patients underwent VP shunt placement. Patients undergoing laparoscopic approach were older and required less preoperative support. Mean operative time was longer with laparoscopy (mean(SD): 74.2(48.1) vs. 64.6(39) minutes, p â€‹< â€‹0.0001) but had shorter hospital LOS. There was no difference in SSI, readmissions, or reoperation rates. CONCLUSION: Patients undergoing laparoscopy for distal VP shunts are older with less support needs preoperatively. While laparoscopic approach had a shorter hospital LOS, there was no demonstratable difference in SSI, readmissions or reoperations between approaches. Further studies are needed to assess long-term outcomes.

Surgical microwave ablation for the treatment of hepatocellular carcinoma in 791 operations.

INTRODUCTION: Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality and often arises in the setting of cirrhosis. The present series reviews outcomes following 791 operations. METHODS: Retrospective review surgical MWA for HCC from March 2007 through December 2022 at a high-volume institution was performed using a prospective database. Primary outcome was overall survival. RESULTS: A total of 791 operations in 623 patients and 1156 HCC tumors were treated with surgical MWA. Median tumor size was 2 cm (range 0.25-10 cm) with an average of 1 tumor ablated per operation (range 1-7 tumors). Nearly 90 % of patients had cirrhosis with a median MELD score of 8 (IQR = 6-11). Mortality within 30 days occurred in 13 patients (1.6 %). Per tumor, the rate of incomplete ablation was 2.25 % and local recurrence was 2.95 %. Previous ablation and tumor size were risk factors for recurrence. One-year overall survival was 82.0 % with a median overall survival of 36.5 months (95 % CI 15.7-93.7) and median disease-free survival of 15.9 months (range 5.7-37.3 months). CONCLUSION: Surgical MWA offers a low-morbidity approach for treatment of HCC, affording low rates of incomplete ablation and local recurrence.

Expanding the utility of robotics for pancreaticoduodenectomy: a 10-year review and comparison to international benchmarks in pancreatic surgery.

BACKGROUND: Robotic pancreaticoduodenectomy (RPD) is an emerging alternative to open pancreaticoduodenectomy (OPD). Although RPD offers various theoretical advantages, it is used in less than 10% of all pancreaticoduodenectomies. The aim of this study was to report our 10-year experience and compare RPD outcomes with international benchmarks for OPD. METHODS: A retrospective review of a prospectively maintained institutional database was performed of consecutive patients who underwent RPD between January 2011 and December 2021. Patients were categorized into low-risk and high-risk groups according to the selection criteria set by the benchmark study. Their outcomes were compared to the international benchmark cut off values. Outcomes were then evaluated over time to identify improvements in practice and establish a learning curve. RESULTS: Of 201 RPDs, 36 were low-risk and 165 high-risk patients. Compared to the OPD benchmarks, outcomes of low-risk patients were within the cutoff values. High-risk patients were outside the cutoff for blood transfusions (26% vs. ≤ 23%), overall complications (78% vs. ≤ 73%), grade I-II complications (68% vs. ≤ 62%), and readmissions (22% vs ≤ 21%). Oncologic outcomes for high-risk patients were within benchmark cutoffs. Cases at the end of the learning curve included more pancreatic cancer (42% from 17%) and fewer low-risk patients (10% from 24%) than those at the beginning. After 41 RPD there was a decline in conversion rates and operative time. Between 95 and 143 cases operative time, transfusion rates, and LOS declined significantly. Complications did not differ over time. CONCLUSION: RPD yields results comparable to the established benchmarks in OPD in both low- and high-risk patients. Along the learning curve, RPD evolved with the inclusion of more high-risk cases while outcomes remained within benchmarks. Addition of a robotic HPB surgery fellowship did not compromise outcomes. These results suggest that RPD may be an option for high-risk patients at specialized centers.

Major hepatectomy in elderly patients: possible benefit from robotic platform utilization.

INTRODUCTION: Robotic surgery has been increasingly utilized, yet its application for hepato-pancreato-biliary (HPB) procedures remains low due to technical complexity, perceived financial burden, and unproven clinical benefits. We hypothesized that the robotic approach would be associated with improved clinical outcomes following major hepatectomy compared with the laparoscopic approach among elderly patients who would benefit from the advantages of minimally invasive surgery. METHODS: A retrospective review of consecutive patients who underwent major hepatectomy between January 2010 and December 2021 at Carolinas Medical Center was performed. Inclusion criteria were age ≥ 65 years and major hepatectomy of three segments or more. Patients who underwent multiple liver resections, vascular/biliary reconstruction, or concomitant extrahepatic procedures (except cholecystectomy) were excluded. Categorical variables were compared using Chi-square or Fisher's exact test when more than 20% of cells had expected frequencies less than five, and Wilcoxon two-sample or Kruskal-Wallis tests were used for continuous or ordinal variables. Results are described as median and interquartile range (IQR). Multivariate analyses were used on postoperative admission days. RESULTS: There were 399 major hepatectomies performed during this time period, of which 125 met the criteria and were included. There were no differences in perioperative demographics among patients who underwent robotic hepatectomy (RH, n = 39) and laparoscopic hepatectomy (LH, n = 32). There was no difference in operative time, blood loss, or major complication rates. However, RH had lower rates of conversion to an open procedure (2.6% versus 31.3%, p = 0.002), shorter length of hospital stay [LOS, 4 (3-7) versus 6 (4-8.5) days, p ≤ 0.0001], cumulative LOS [4 (3-7) versus 6 (4.5-9) days, p ≤ 0.0001], and lower rates of intensive care unit (ICU) admission (7.7% versus 75%, p ≤ 0.001), with a trend toward fewer rehabilitation requirements. CONCLUSIONS: Robot major hepatectomy shows clinical advantages in elderly patients, including shorter hospital and ICU stays. These advantages, as well as reduced rehabilitation requirements associated with minimally invasive surgery, could overcome the current perceived financial disadvantages of robotic hepatectomy.

Impact of COVID-19 on common non-elective general surgery diagnoses.

BACKGROUND: During the COVID-19 pandemic, public health and hospital policies were enacted to decrease virus transmission and increase hospital capacity. Our aim was to understand the association between COVID-19 positivity rates and patient presentation with EGS diagnoses during the COVID pandemic compared to historical controls. METHODS: In this cohort study, we identified patients ≥ 18 years who presented to an urgent care, freestanding ED, or acute care hospital in a regional health system with selected EGS diagnoses during the pandemic (March 17, 2020 to February 17, 2021) and compared them to a pre-pandemic cohort (March 17, 2019 to February 17, 2020). Outcomes of interest were number of EGS-related visits per month, length of stay (LOS), 30-day mortality and 30-day readmission. RESULTS: There were 7908 patients in the pre-pandemic and 6771 in the pandemic cohort. The most common diagnoses in both were diverticulitis (29.6%), small bowel obstruction (28.8%), and appendicitis (20.8%). The lowest relative volume of EGS patients was seen in the first two months of the pandemic period (29% and 40% decrease). A higher percentage of patients were managed at a freestanding ED (9.6% vs. 8.1%) and patients who were admitted were more likely to be managed at a smaller hospital during the pandemic. Rates of surgical intervention were not different. There was no difference in use of ICU, ventilator requirement, or LOS. Higher 30-day readmission and lower 30-day mortality were seen in the pandemic cohort. CONCLUSIONS: In the setting of the COVID pandemic, there was a decrease in visits with EGS diagnoses. The increase in visits managed at freestanding ED may reflect resources dedicated to supporting outpatient non-operative management and lack of bed availability during COVID surges. There was no evidence of a rebound in EGS case volume or substantial increase in severity of disease after a surge declined.

Timing of venous thromboembolism chemoprophylaxis using objective hemoglobin criteria in blunt solid organ injury.

BACKGROUND: The purpose of this study was to evaluate the safety and efficacy of early venous thromboembolism (VTE) chemoprophylaxis following blunt solid organ injury. METHODS: A retrospective review of patients was performed for patients with blunt solid organ injury between 2009-2019. Enoxaparin was initiated when patients had <1g/dl Hemoglobin decline over a 24 h period. These patients were then categorized by initiation: ≤48 h and >48 h. RESULTS: There were 653 patients: 328 (50.2%) <48 h and 325 (49.8%) ≥48 h. Twenty-nine (4.4%) developed VTE. Patients in ≥48 h group suffered more frequent VTE events (6.5% vs 2.4%, p = 0.021). Non-operative failure occurred in 6 patients (1.9%) in ≥48 h group, and 5 patients (1.5%) < 48 h group. Blood transfusion following chemophrophylaxis initiation was required in 69 (21.3%) in ≥48 h group, and 46 (14.0%) in < 48 h group, occurring similarly between groups (p=0.021). CONCLUSION: Stable hemoglobin in the first 24 h is an efficacious, objective measure that allows early initiation of VTE chemoprophylaxis in solid organ injury. This practice is associated with earlier initiation of and fewer VTE events.

Effects of Guideline-Based Correction of Platelet Inhibition on Outcomes in Moderate to Severe Isolated Blunt Traumatic Brain Injury.

Platelet dysfunction has been demonstrated after traumatic brain injury (TBI) regardless of the use of platelet inhibitors. The purpose of this study was to determine the efficacy of a platelet-mapping thromboelastography (PM-TEG) in predicting TBI patients who would benefit from platelet transfusion. We hypothesized that adenosine diphosphate (ADP) and arachadonic acid (AA) inhibition in patients with TBI is associated with increased mortality and can be corrected with platelet transfusion. This is a retrospective review of patients admitted to a level 1 trauma center from January 2016 through September 2017 with moderate to severe blunt TBI (msTBI), defined by an initial Glasgow Coma Scale (GCS) ≤12 with intracranial hemorrhage. Patients received PM-TEG. Those with platelet dysfunction (ADP or AA inhibition ≥60%) received one unit of platelets followed by repeat PM-TEG, until inhibition <60% or three units of platelets. Cohorts were defined as patients initially without (NPI) and with (PI) inhibition and subdivided into those whose inhibition corrected (PI-C) versus those whose did not correct (PI-NC). From 69 patients with isolated blunt TBI, 40 (58%) presented with NPI, 29 (42%) with PI. Of those with PI, 16 (55%) were with PI-C and 13 (45%) with PI-NC. Platelet inhibition in msTBI patients undergoing guideline-based transfusion is associated with age and GCS and an increase in mortality. Platelet inhibition seems to have a more adverse effect on patients >55 years of age or with GCS <8. Correction of platelet inhibition normalized mortality to that of NPI.

Dynamic Response of CFRP Reinforced Steel Beams Subjected to Impact Action Based on FBG Sensing Technology.

The in-situ health condition of carbon fiber reinforced polymer (CFRP) reinforced structures has become an important topic, which can reflect the structural performance of the retrofitted structures and judge the design theory. An optical fiber-based structural health monitoring technique is thus suggested. To check the effectiveness of the proposed method, experimental testing on smart CFRP reinforced steel beams under impact action has been performed, and the dynamic response of the structure has been measured by the packaged FBG sensors attached to the surface of the beam and the FBG sensors inserted in the CFRP plates. Time and frequency domain analysis has been conducted to check the structural feature of the structures and the performance of the installed sensors. Results indicate that the packaged Fiber Bragg Grating (FBG) sensors show better sensing performance than the bare FBG sensors in perceiving the impact response of the beam. The sensors embedded in the CFRP plate show good measurement accuracy in sensing the external excitation and can replace the surface-attached FBG sensors. The dynamic performance of the reinforced structures subjected to the impact action can be straightforwardly read from the signals of FBG sensors. The larger impact energies bring about stronger impact signals.

Wiping conditions and fabric properties influenced the microfiber shedding from non-woven products.

Disposable wipes and masks have come to be considered as underestimated sources of microfiber generation since the emergence of COVID-19. However, research into the creation of microfibers due to wiping with these non-woven products is scarce, and the potential effects of fabric properties on shedding behavior are unclear. This study investigated microfiber release from 7 wet wipes, 5 dry wipes, and 4 masks in response to the use of simulated daily wiping conditions on artificial skin. The dry wipes (77-568 p per sheet) shed more microfibers than the wet ones (21-190 p per sheet) after 2, 10, or 50 wiping cycles under a 9.8 N wiping force. In addition, an average of 56 microfibers could be released from per gram of wipe, and each square centimeter of wipe could release about 1.18 microfibers during wiping. Masks shed fewer microfibers than wipes due to the excellent shedding resistance of spunbond nonwoven fabrics and the strengthened mechanical properties granted by bonding points. Cellulose, polyethylene terephthalate (PET), and polypropylene (PP) were the major polymers in the microfibers shed by wipes, and the microfibers from masks were all PP. With regard to the influencing factors, the number of microfibers shed from wipes was positively associated with the number of wiping cycles (r = 0.983 and 0.960, p < 0.01) and wiping force (r = 0.980, p < 0.05), while it was negatively correlated with the moisture content (r = -0.992, p < 0.01). Interestingly, a stronger fiber entanglement degree in the wipes significantly improved the resistance to microfiber generation (r = -0.664, p < 0.05). The results highlighted for the first time that the bending coefficient (ß = -5.05; 95% CI: -7.71, -2.40; p = 0.002) and fiber extraction force (ß = -0.077; 95% CI: -0.123, -0.030; p = 0.005) significantly reduced the tendency for microfiber shedding. Although the number of microfibers shed from wiping was lower than those from domestic washing, there is still an urgent need to control the microfiber shedding tendencies of non-woven products through improving the manufacturing processes.

The physiology of failure: Identifying risk factors for mortality in emergency general surgery patients using a regional health system integrated electronic medical record.

BACKGROUND: Emergency general surgery (EGS) patients have increased mortality risk compared with elective counterparts. Recent studies on risk factors have largely used national data sets limited to administrative data. Our aim was to examine risk factors in an integrated regional health system EGS database, including clinical and administrative data, hypothesizing that this novel process would identify clinical variables as important risk factors for mortality. METHODS: Our nine-hospital health system's billing data were queried for EGS International Classification of Disease codes between 2013 and 2018. Codes were grouped by diagnosis, and urgent or emergent encounters were included and merged with electronic medical record clinical data. Outcomes assessed were inpatient and 1-year mortality. Standard and multivariable statistics evaluated factors associated with mortality. RESULTS: There were 253,331 EGS admissions with 3.6% inpatient mortality rate. Patients who suffered inpatient and 1-year mortality were older, more likely to be underweight, and have neutropenia or elevated lactate. On multivariable analysis for inpatient mortality: age (odds ratio [OR], 1.7-6.7), underweight body mass index (OR, 1.6), transfer admission (OR, 1.8), leukopenia (OR, 2.0), elevated lactate (OR, 1.8), and ventilator requirement (OR, 7.1) remained associated with increased risk. Adjusted analysis for 1-year mortality demonstrated similar findings, with highest risk associated with older age (OR, 2.8-14.6), underweight body mass index (OR, 2.3), neutropenia (OR, 2.0), and tachycardia (OR, 1.7). CONCLUSION: After controlling for patient and disease characteristics available in administrative databases, clinical variables remained significantly associated with mortality. This novel yet simple process allows for easy identification of clinical data points imperative to the study of EGS diagnoses that are critical in understanding factors that impact mortality. LEVEL OF EVIDENCE: Prognostic and Epidemiologic; Level III.

Safety of Primary Versus Revisional Biliopancreatic Diversion with Duodenal Switch in Patients with Super Obesity Using the MBSAQIP database.

INTRODUCTION: For patients with super obesity (BMI > 50 kg/m2), biliopancreatic diversion/duodenal switch (BPD/DS) can be an effective bariatric operation. Technical challenges and patient safety concerns, however, have limited its use as a primary procedure. This study sought to assess the safety of primary versus revisional BPD/DS. MATERIALS AND METHODS: The MBSAQIP database was queried for primary and revisional BPD/DS (2015-2018). Inclusion criteria were patients ≥ 18 years of age, BMI > 50 kg/m2, and with no concurrent procedures. Preoperative variables were compared using a chi-square test or Wilcoxon two-sample tests. Multivariate logistic or robust linear regression models were used to compare outcomes. RESULTS: There were 3,378 primary BPD/DS and 487 revisional BPD/DS patients. Primary BPD/DS patients had higher BMI (56.5 [IQR4.4] versus 54.8 [IQR4] kg/m2, p < 0.0001) and had more diabetes mellitus type II (29.1% versus 17.2%, p < 0.0001). Intraoperatively, revisional BPD/DS had longer operative time (165 [IQR47] min versus 139 [IQR100] min, p < 0.0001). After adjusting for preoperative characteristics, there was no difference in 30-day readmission or ED visits (primary 12.9% versus revisional 14.6%), reoperation or reintervention (primary 5.7% versus revisional 7.8%), or mortality (primary 0.4% versus revisional 0.6%). In contrast, the revisional BPD/DS patients had higher odds of major morbidity (primary 3.4% versus revisional 5.3%, OR 1.9, CI 1.1-3.2, p = 0.019). CONCLUSIONS: Revisional BPD/DS is associated with higher morbidity than primary BPD/DS in patients with super obesity. These patients should thus be counselled appropriately when choosing a primary or revisional bariatric procedure.

DCZ0014, a novel compound in the therapy of diffuse large B-cell lymphoma via the B cell receptor signaling pathway.

Diffuse large B cell lymphoma (DLBCL) is a clinical and genetically heterogeneous lymphoid malignancy. Although R-CHOP (rituximab plus cyclophosphamide, vincristine, doxorubicin, and prednisone) treatment can improve the survival rate of patients with DLBCL, more than 30% of patients exhibit treatment failure, relapse, or refractory disease. Therefore, novel drugs or targeted therapies are needed to improve the survival of patients with DLBCL. The compound DCZ0014 is a novel chemical similar to berberine. In this study, we found that DCZ0014 significantly inhibited the proliferation and activity of DLBCL cells, and induced cell apoptosis. Following treatment with DCZ0014, DLBCL cells accumulated in G0/G1-phase of the cell cycle and showed decreased mitochondrial membrane potential. Additionally, DCZ0014 inhibited DNA synthesis, enhanced DNA damage in DLBCL cells, as well as inhibited Lyn/Syk in B cell receptor signaling pathway. Further experiments demonstrated that DCZ0014 did not significantly affect peripheral blood mononuclear cells. Tumor xenograft model showed that DCZ0014 not only inhibited tumor growth but also extended the survival time of mice. Thus, DCZ0014 showed potential for clinical application in the treatment of patients with DLBCL.

Quercetin inhibits the proliferation of multiple myeloma cells by upregulating PTPRR expression.

Multiple myeloma (MM) is an incurable disease characterized by malignant plasma cell clonal expansion in the bone marrow; therefore, inhibiting the proliferation of plasma cells is an important approach to overcome the progression of MM. Quercetin (Que) is a promising flavonoid with broad-spectrum anti-tumor activity against various cancers, including MM; however, the underlying mechanism is not yet understood. The present study aimed to reveal the gene expression profile of Que-treated MM cells and clarify its potential mechanism. The 30% inhibitory concentration (IC30) of Que against MM cells was calculated, and the proliferation rate was significantly reduced after Que treatment. Next, 495 dysregulated genes were identified via RNA sequencing in Que-treated MM cells. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes analyses indicated that the dysregulated genes were enriched in various apoptosis-related GO terms and amino acid metabolism-related pathways. qPCR validation showed that protein tyrosine phosphatase receptor-type R (PTPRR) had the highest verified log2 FC (abs) among the top 15 dysregulated genes. Overexpression of PTPRR increased the sensitivity of MM cells against Que, significantly inhibiting their proliferation and colony formation ability; silencing of PTPRR showed the opposite results. Furthermore, bioinformatics analyses and PPI network construction of PTPRR indicated that dephosphorylation of ERK might be the potential pathway for the PTPRR-induced inhibition of MM cell proliferation. In summary, our study identified the gene expression profile in Que-treated MM cells and demonstrated that the upregulation of PTPRR was one of the important mechanisms for the Que-induced inhibition of MM cell proliferation.

Critical care ultrasound in geriatric trauma resuscitation leads to decreased fluid administration and ventilator days.

BACKGROUND: Geriatric trauma populations respond differently than younger trauma populations. Critical care ultrasound (CCUS) can guide resuscitation, and it has been shown to decrease intravenous fluid (IVF), lower time until operation, and lower mortality in trauma. Critical care ultrasound-guided resuscitation has not yet been studied in geriatric trauma. We hypothesized that incorporation of CCUS would decrease amount of IVF administered, decrease time to initiation of vasopressors, and decrease end organ dysfunction. METHODS: A PRE-CCUS geriatric trauma group between January 2015 and October 2016 was resuscitated per standard practice. A POST-CCUS group between January 2017 and December 2018 was resuscitated based on CCUS performed by trained intensivist upon admission to the intensive care unit and 6 hours after initial ultrasound. The PRE-CCUS and POST-CCUS groups underwent propensity score matching, yielding 60 enrollees in each arm. Retrospective review was conducted for demographics, clinical outcomes, and primary endpoints, including amount of IVF in the first 48 hours, duration to initiation of vasopressor use, and end organ dysfunction. Wilcoxon two-sample, χ2 tests, and κ statistics were performed to check associations between groups. RESULTS: There was no statistical difference between PRE-CCUS and POST-CCUS demographics and Injury Severity Scores. Intravenous fluid within 48 hours decreased from median [interquartile range] of 4941 mL [4019 mL] in the PRE-CCUS to 2633 mL [3671 mL] in the POST-CCUS (p = 0.0003). There was no significant difference between the two groups in time to initiation of vasopressors, vasopressor duration, lactate clearance, intensive care unit length of stay, or hospital length of stay. There was a significant decrease in ventilator days, with 26.7% PRE-CCUS with ventilation longer than 2 days, and only 6.7% POST-CCUS requiring ventilation longer than 2 days (p = 0.0033). CONCLUSION: Critical care ultrasound can be a useful addition to geriatric resuscitation. The POST-CCUS received less IV fluid and had decreased ventilator days. While mortality, lactate clearance, complications, and hospital stay were not statistically different, there was a perception that CCUS was a useful adjunct for assessing volume status and cardiac function. LEVEL OF EVIDENCE: Therapeutic, level II.

Gas sensing materials roadmap.

Gas sensor technology is widely utilized in various areas ranging from home security, environment and air pollution, to industrial production. It also hold great promise in non-invasive exhaled breath detection and an essential device in future internet of things. The past decade has witnessed giant advance in both fundamental research and industrial development of gas sensors, yet current efforts are being explored to achieve better selectivity, higher sensitivity and lower power consumption. The sensing layer in gas sensors have attracted dominant attention in the past research. In addition to the conventional metal oxide semiconductors, emerging nanocomposites and graphene-like two-dimensional materials also have drawn considerable research interest. This inspires us to organize this comprehensive 2020 gas sensing materials roadmap to discuss the current status, state-of-the-art progress, and present and future challenges in various materials that is potentially useful for gas sensors.

Using Platelet-Rich Plasma Hydrogel to Deliver Mesenchymal Stem Cells into Three-Dimensional PLGA Scaffold for Cartilage Tissue Engineering.

The synthetic biodegradable polyester-based rigid porous scaffolds and cell-laden hydrogels have been separately employed as therapeutic modality for cartilage repair. However, the synthetic rigid scaffolds alone may be limited due to the inherent lack of bioactivity for cartilage regeneration, while the hydrogels have insufficient mechanical properties that are not ideal for load-bearing cartilage applications. In the present study, a hybrid construct was designed to merge the advantage of 3D-printed rigid poly(lactic-co-glycolic acid) (PLGA) scaffolds with cell-laden platelet-rich plasma (PRP) hydrogels that can release growth factors to regulate the tissue healing process. PRP hydrogels potentially achieved the effective delivery of mesenchymal stem cells (MSCs) into PLGA scaffolds. This hybrid construct could obtain adequate mechanical properties and independently provide MSCs with appropriate clues for proliferation and differentiation. Real-time gene expression analysis showed that PRP stimulated both chondrogenic and osteogenic differentiation of MSC seeding into PLGA scaffolds. Finally, the hybrid constructs were implanted into rabbits to simultaneously regenerate both articular cartilage and subchondral bone within osteochondral defects. Our findings suggest that this unique hybrid system could be practically applied for osteochondral regeneration due to its capacity for cell transportation, growth factors release, and excellent mechanical strength, which would greatly contribute to the progress of cartilage tissue engineering.