Efficacy and Safety of Enhanced Recovery After Surgery (ERAS) Protocols for Patients Undergoing Minimally Invasive Transforaminal Lumbar Interbody Fusion Surgery: A Systematic Review and Meta-Analysis.

OBJECTIVE: To evaluate the efficacy and safety of enhanced recovery after surgery (ERAS) in minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF) for lumbar degenerative disease (LDD). METHODS: Electronic databases including PubMed, Embase, the Cochrane Library, Web of Science, Clinical Trials.gov, etc. were searched from inception to October 2023. Randomized controlled trials (RCTs) and cohort studies (CSs) comparing ERAS program with traditional protocol of MIS-TLIF for LDD were included. RESULTS: A total of 11 studies were included for final analysis. The pooled results of RCTs showed that compared with MIS-TLIF, the ERAS program used in MIS-TLIF could reduce the length of hospital stay, operation time, intraoperative blood loss and incidence of postoperative complications, decrease visual analog scale and Oswestry Disability Index (ODI) score, and improve patient satisfaction (P < 0.05). However, the pooled results of CSs revealed no statistical difference in the ODI score, fusion rate, operation time, and incidence of complications between the two groups (P > 0.05). CONCLUSIONS: Compared with MIS-TLIF, the ERAS program used in MIS-TLIF could effectively shorten the length of hospital stay, operation time, decrease intraoperative blood loss, and incidence of postoperative complications, promote postoperative pain relief, functional recovery, and patient satisfaction. This study confirmed the value of ERAS in MIS-TLIF surgery and provided evidence for the standardization of ERAS in the future. Considering that the pooled results of RCTs and CSs are not completely consistent, more high-quality studies are needed to confirm these conclusions.

Efficacy and Safety of Bilateral Ultrasound-Guided Erector Spinae Plane Block for Postoperative Analgesia in Spine Surgery: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

OBJECTIVE: A meta-analysis of randomized controlled trials was conducted to assess efficacy and safety of bilateral ultrasound-guided erector spinae plane block (ESPB) for postoperative analgesia in patients receiving spine surgery. METHODS: PubMed, Embase, and CENTRAL databases were searched by 2 reviewers independently to identify randomized controlled trials evaluating the efficacy of ultrasound-guided ESPB for pain management in patients undergoing spine surgery. For meta-analysis, mean difference (MD) and 95% confidence interval (CI) were selected for continuous data, and risk ratio (RR) and 95% CI were selected for dichotomous variables. RESULTS: A total of 25 randomized controlled trials including 1917 patients (873 in ESPB group and 874 in control group) were eligible for inclusion. At rest, ESPB was associated with significantly lower pain intensity at 0, 2, 4, 6, 8, 12, 24, and 48 hours compared with the control group. During movement, ESPB was associated with significantly lower pain intensity at 0, 4, 6, 8, 12, 24, and 48 hours compared with the control group. Significantly reduced opioid consumption (MD = -6.29, 95% CI [-8.16, 4.41], P < 0.001), prolonged time for first rescue analgesia (MD = 7.51, 95% CI [3.47, 11.54], P < 0.001), fewer patients needing rescue analgesia (RR = 0.34, 95% CI [0.28, 0.43], P < 0.0001), improved patient satisfaction (MD = 1.34, 95% CI [0.88, 1.80], P < 0.001), and shorter length of hospital stay (MD = -0.38, [95% CI -0.50, -0.26], P < 0.001) were demonstrated after use of ESPB. Additionally, ESPB was associated with decreased risks of any adverse event (RR = 0.51, 95% CI [0.43, 0.60], P < 0.001) and postoperative nausea and vomiting events (RR = 0.39, 95% CI [0.31, 0.49], P < 0.001). CONCLUSIONS: Ultrasound-guided ESPB is an effective adjunctive technique with good tolerability for multimodal analgesia in management of pain in patients undergoing spine surgery.

Functional analysis of polyphenol oxidase 1 gene in common wheat.

Polyphenol oxidase (PPO) activity is a major cause of the undesirable brown color of wheat-based products. Ppo1, a major gene for PPO activity, was cloned based on sequence homology in previous studies; however, its function and regulation mechanism remain unclear. In this study, the function and genetic regulation of Ppo1 were analyzed using RNA interference (RNAi) and Targeting Induced Local Lesions IN Genomes (TILLING) technology, and superior mutants were identified. Compared with the control, the level of Ppo1 transcript in RNAi transgenic lines was drastically decreased by 15.5%-60.9% during grain development, and PPO activity was significantly reduced by 12.9%-20.4%, confirming the role of Ppo1 in PPO activity. Thirty-two Ppo1 mutants were identified in the ethyl methanesulfonate (EMS)-mutagenized population, including eight missense mutations, 16 synonymous mutations, and eight intron mutations. The expression of Ppo1 was reduced significantly by 6.7%-37.1% and 10.1%-54.4% in mutants M092141 (G311S) and M091098 (G299R), respectively, in which PPO activity was decreased by 29.7% and 28.8%, respectively, indicating that mutation sites of two mutants have important effects on PPO1 function. Sequence and structure analysis revealed that the two sites were highly conserved among 74 plant species, where the frequency of glycine was 94.6% and 100%, respectively, and adjacent to the entrance of the hydrophobic pocket of the active site. The M092141 and M091098 mutants can be used as important germplasms to develop wheat cultivars with low grain PPO activity. This study provided important insights into the molecular mechanism of Ppo1 and the genetic improvement of wheat PPO activity.

Identification of lower brominated bisphenol A analogs as the photooxidation products of tetrabromobisphenol A bis(2,3-dibromopropyl) ether (TBBPA-BDBPE).

The transformation products and mechanism of tetrabromobisphenol A (TBBPA) derivatives are still largely unknown compared with TBBPA. In this paper, sediment, soil and water samples (15 sites, 45 samples) collected in a river flowing through brominated flame retardant manufacturing zone were analyzed to determine TBBPA derivatives, byproducts, and transformation products. TBBPA derivatives and byproducts were detected with concentrations ranging from none detection to 1.1 × 104 ng/g dw and with detection frequencies of 0-100 % in all samples. The concentrations of TBBPA derivatives such as TBBPA bis(2,3-dibromopropyl) ether (TBBPA-BDBPE) and TBBPA bis(allyl ether) in sediment and soil samples were higher than that of TBBPA. In addition, the occurrence of various unknown bromobisphenol A allyl ether analogs in the samples was further confirmed by using 11 synthesized analogs, which might be produced during the waste treatment process of the factories. The possible transformation pathways of TBBPA-BDBPE were revealed for the first time by using UV/base/persulfate (PS) as designed photooxidation waste treatment system in the laboratory. Ether bond cleavage, debromination, and ß-scission contributed to the transformation of TBBPA-BDBPE and the occurrence of transformation products in the environment. The concentrations of the transformation products of TBBPA-BDBPE ranged from none detection to 3.4 × 102 ng/g dw. These data provide new insights into the fate of TBBPA derivatives in environmental compartments.

Icariin-conditioned serum combined with chitosan attenuates cartilage injury in rabbit knees with osteochondral defect.

BACKGROUND: Knee osteoarthritis (KOA) is one of the most common degenerative diseases. Its development is closely related to cartilage injury and subchondral bone remodeling homeostasis. In the present study, we combined icariin-conditioned serum (ICS) with thiolated chitosan (CSSH), a material widely used in tissue engineering for cartilage repair, to demonstrate its effect on the repair of cartilage damage and abnormal subchondral remodeling. METHODS: New Zealand rabbits were undergoing surgery for cartilage defect, and joint cavity injection was performed in each group with 0.5 mL normal saline (NS), ICS, CSSH and ICS-CSSH in the right joint every week for five times. Positioning performance was observed using VICON motion capture system. Glycosaminoglycans (GAG) secretion of articular fluid was assessed. Osteoarthritis Research Society International (OARSI) score and immunohistochemical (IHC) analysis including H&E, Safranin O and collagen II staining were employed to evaluate the morphologic repair of cartilage and subchondral bone. mRNA expression of COL2A1, MMP13 and ADAMTS5 was detected in chondrocytes from injury area. RESULTS: ICS combined with CSSH attenuated cartilage injury and abnormal subchondral remodeling in rabbits with KOA. ICS and CSSH groups showed slight improvement in positioning performance, while ICS-CSSH group exhibited better positioning performance. ICS-CSSH group showed increased GAG secretion of articular fluid and expression of COL2A1 in articular chondrocytes. Furthermore, both macroscopic observation and IHC analysis showed femoral condyle in ICS-CSSH rabbits were repaired with more native cartilage and subchondral bone regeneration. CONCLUSIONS: ICS combined with CSSH could promote the repair of osteochondral defect and stabilize subchondral bone remodeling in rabbit knees.

Efficacy and safety of tension band wire versus plate for Mayo II olecranon fractures: a systematic review and meta-analysis.

PURPOSE: For olecranon fractures, the choice of tension band wire (TBW) or plate fixation has long been controversial. Therefore, this study aimed to evaluate the efficacy and safety of TBW and plate in the treatment of patients with Mayo II olecranon fractures by Meta-analysis. METHODS: PubMed, Embase, Cochrane, the Web of Science, China National Knowledge Infrastructure, Wanfang, and China Biomedical Database were searched for randomized controlled trials (RCTs) and cohort studies (CSs) where TBW was compared with plate for Mayo II olecranon fractures (OF). Subsequently, the data were extracted by two reviewers independently and were analysed via RevMan5.4.1. Besides, mean difference (MD), risk ratio (RR), and 95% confidence intervals (CIs) were calculated. Furthermore, Cochrane Risk of Bias Tool 2.0 and Newcastle-Ottawa Scale were adopted for assessing the risk of bias. RESULTS: A total of 1RCT and 10 CSs were included, when 449 cases were treated with TBW and 378 with plate. The plate has favourable postoperative long-term (≥ 1 year) functional score in MEPS (MD: - 3.06; 95% CI - 5.50 to 0.62; P = 0.01; I2 = 41%) and Dash score (MD: 2.32; 95% CI 1.91, 2.73; P < 0.00001; I2 = 0%), also carrying fewer complications (RR: 2.13; 95% CI 1.48, 3.08; P < 0.0001; I2 = 58%). Besides, there exists no significant difference in postoperative long-term (≥ 1 year) elbow flexion (MD: - 1.82°; 95% CI - 8.54, 4.90; P = 0.60; I2 = 71%) and extension deficits (MD: 1.52°; 95% CI - 0.38, 3.42; P = 0.12; I2 = 92%). Moreover, TBW is featured with a shorter operation time (MD = - 5.87 min; 95% CI - 7.93, - 3.82; P < 0.00001; I2 = 0) and less intraoperative bleeding (MD: - 5.33 ml; 95% CI - 8.15, - 2.52; P = 0.0002; I2 = 0). In terms of fracture healing time, it is still controversial. Furthermore, the subgroup analysis has revealed that for Mayo IIA OF, the plate has a better outcome in the long-term (≥ 1 year) postoperative MEPS, the Dash score, and the incidence of postoperative complications than TBW, while there is no significant difference in the long-term (≥ 1 year) postoperative elbow motion between two groups. CONCLUSIONS: Plate has better efficacy and safety for Mayo II OF. Considering that few studies are included in the meta-analysis, more high-quality RCTs are still required to confirm these findings. PROSPERO registration number: CRD42022313855.

Study of the scavenger and vector roles of microplastics for polyhalocarbazoles under simulated gastric fluid conditions.

Microplastics entering the digestive system of living organisms can serve as a carrier of hydrophobic organic pollutants (HOPs), increasing their exposure levels and the health risks they pose to both humans and animals. The desorption kinetics of six polyhalocarbazoles (PHCZs) from 5 mm and 0.15 mm polypropylene (PP) and polyvinyl chloride (PVC) microplastic particles were assessed using a combined microplastics and food system, representing the gastric system of vertebrates and invertebrates. Results showed that the chemical transfer of PHCZs is biphasic and reversible, with rapid exchange occurring within 2-48 h, followed by a period of slow transfer, which continues for weeks to months. The desorption capacity of PHCZs loaded on 0.15 mm microplastic particles was greater than that of 5 mm particles. The bioavailability percentage of PHCZ congeners for PP (24.2%-65.3%) and PVC (43.5%-57.2%) in the vertebrate fluid system were all lower than those in the invertebrate system (34.2%-70.7% for PP and 56.3%-72.7% for PVC, respectively). These findings indicate that physiological conditions, such as polarity, ingestion fluid, and microplastic affect the desorption of PHCZs from microplastics. In addition, desorption from PP was inhibited by the presence of foodstuff loaded with PHCZs due to competition, while desorption from PVC was not significantly affected by the presence of PHCZs contaminant food. Microplastics could provide a cleaning function in gastric fluid systems containing contaminated foodstuff, especially PP, which was capable of competitive adsorption of PHCZs from food. Few investigations have focused on the adverse effects of microplastic ingestion on human health, particularly in their role as vectors for HOPs, compared to other routes of exposure and transport. Therefore, these findings provide valuable insight into the health risks associated with dietary intake of microplastics and HOPs.

Fate and ecological risks of current-use pesticides in seawater and sediment of the Yellow Sea and East China Sea.

With the frequent use of chemical pesticides, the current-use pesticides (CUPs) emerge and concentrate in the sea. The partition between the sediment and seawater is essential for understanding the environmental fate of CUPs. However, there is little research on this topic. In the present study, seventeen CUPs were screened in seawater and sediment samples collected from the Yellow Sea and East China Sea. Total concentration of 17 CUPs in surface seawater samples ranged from 9.5 to 267.3 ng/L, with 6 CUPs presenting 100% detection frequency. Carbendazim, tricyclazole, tebuconazole, atrazine and imidacloprid accounted for >80% of all CUPs, which was due to their large application in the local agriculture and fishing activities. Higher concentration sites were located near the shore and Yangtze river estuary, indicating intense human activities and riverine input that elevated the level of CUPs in marginal sea. The pesticides in seawater were mainly found in the surface followed by the bottom layer, which indicated that atmospheric deposition and re-suspension played key roles for their vertical distribution characteristics. The high fugacity fraction ratios (ff > 0.5) indicated the non-equilibrium state of pesticides that might have been transferred from sediment to seawater at most sites. These 17 detectable pesticides in seawater were at low levels, presenting ignorable or low toxic effects to aquatic organisms.

Tourniquet application in primary total knee arthroplasty for osteoarthritis: A systematic review and meta-analysis of randomized controlled trials.

Objective: The aim of this study was to identify the influence of a tourniquet on the blood loss, transfusion requirement, swelling, pain, knee function, range of motion (ROM), operation time, bone cement mantle thickness, and complications in patients operated with total knee arthroplasty (TKA). Methods: Two authors independently retrieved PubMed, Embase, and CENTRAL to identify eligible randomized controlled trials (RCTs) evaluating the effectiveness of a tourniquet in TKA. Fixed- (I 2 < 50%) or random-effects (I 2 > 50%) models were selected to perform meta-analysis according to the value of I 2. Mean difference (MD) and risk ratio were selected as the effect sizes for continuous and dichotomous variables, respectively. Results: A total of 29 RCTs, involving 2,512 operations (1,258 procedures with a tourniquet and 1,254 procedures without a tourniquet), were included, and 18 outcomes were compared. Tourniquet application could significantly decrease intraoperative blood loss (MD = -138.72 ml, p < 0.001), shorten operation duration (MD = -1.77 min, p < 0.001), and increase cement mantle thickness (MD = 0.17 mm, p < 0.001). However, it was significantly associated with increased postoperative pain intensity, decreased full ROM/flexion ROM/extension ROM, poorer knee function, increased knee swelling, and increased length of hospital stay (LOS) at several follow-up points (p < 0.050). No significant difference was found for postoperative draining volume, total blood loss, transfusion rate, change of Hb level, and risks of deep venous thrombosis and all complications. Conclusions: Tourniquet application could only decrease the intraoperative blood loss but has no effectiveness on the total blood loss and transfusion requirement. On the contrary, it has a reverse effect on the pain score, knee function, ROM, swelling, and LOS.

Efficacy and Safety of Oblique Lumbar Interbody Fusion Versus Transforaminal Lumbar Interbody Fusion for Degenerative Lumbar Spondylolisthesis: A Systematic Review and Meta-Analysis.

OBJECTIVE: We critically evaluated the efficacy and safety of oblique lumbar interbody fusion (OLIF) versus transforaminal lumbar interbody fusion (TLIF) for degenerative lumbar spondylolisthesis (DLS). METHODS: PubMed, Embase, Cochrane Library, the Web of Science Core Collection, Chinese Biomedical Literature, China National Knowledge Infrastructure, Wanfang Digital Periodicals, and Chinese Science and Technology Periodicals were searched from their inception to February 2021. Randomized controlled trials and retrospective or prospective cohort studies (CSs) comparing OLIF and TLIF for DLS were included. A meta-analysis was conducted, if possible. RESULTS: Ten studies were included in the statistical analysis. The pooled results of the CSs showed no statistically significant differences (P > 0.05) in pain relief at 3 or 6 months of follow-up and functional improvement at 1 or 3 months of follow-up in DLS patients between those who had undergone OLIF versus TLIF. The pooled results of the CSs showed that OLIF could significantly improve the degree of lumbar lordosis, foraminal height, and disc height and decrease the intraoperative blood loss, postoperative drainage volume, operative duration, bed rest time, and hospital length of stay (P < 0.05) compared with TLIF. The incidence of adverse events was not significantly different statistically between OLIF and TLIF. CONCLUSIONS: The results from the present study suggest that pain relief and functional improvement were not significantly different between OLIF and TLIF. Nevertheless, the use of OLIF might improve radiological outcomes and reduce intraoperative blood loss, postoperative drainage volume, operative duration, bed rest duration, and hospital length of stay compared with TLIF. Additional high-quality randomized controlled trials are still required to confirm these findings.

Synthesis of Icariin-Zinc and its Protective Effect on Exercise Fatigue and Reproductive System Related Glands in Male Rats.

Background: Icariin, a traditional Chinese medicine, plays a protective role in the treatment of exercise fatigue. Zinc, a trace element, plays an important role in the reproductive system. Therefore, we aimed to synthesize an Icariin-Zinc complex (by chemical means) and verify its protective effect on exercise fatigue and the reproductive system using animal experiments. Methods: The icariin-zinc complex was prepared by the reaction of icariin carbonyl and zinc ions (molar ratio 1:3). The molecular formula and structural formula of the complex were identified and tested. Fifty-six rats selected by swimming training were randomly divided into six groups: static control, exercise control, icariin, gluconate zinc (G-Zn group), icariin glucose zinc and icariin-zinc exercise ( low, high dose/L-E group, H-E group) groups. These groups respectively received the following doses: 1 ml/100 g, daily gavage with NS (for the first two groups), 45 mg/kg icariin, 110 mg/kg Gluconate Zinc, Icariin glucose zinc (45 mg/kg Icariin and 110 mg/kg Gluconate Zinc), 60 mg/kg icariin zinc and 180 mg/kg icariin zinc. After 3 weeks of gavage, we conducted 6 weeks of exhaustive swimming training. Test indices such as exhaustive swimming time of rats and body weight were evaluated after the last training exercise. The seminal vesicles, testes, and prostate gland were weighed, and their indices were calculated. The levels of testosterone (in the plasma) and glycogen (in the liver and muscle homogenates) were also evaluated using ELISA. Results: Compared with the static control group, the exhaustive swimming time of the rats in each group was prolonged. Compared with the other groups, the exhaustive swimming time of the L-E and H-E groups was significantly longer (p < 0.01); the Icariin-Zinc complex significantly increased the exhaustive swimming time of the rats. Compared with the static control group, the plasma testosterone content of the L-E and H-E groups increased significantly (p < 0.05). Compared with the exercise control group and G-Zn group, the plasma testosterone content of the H-E group also increased significantly (p < 0.01). The Icariin-Zinc complex significantly increased the serum levels of testosterone in rats. Compared with the control group, the muscle glycogen reserves of each group decreased, indicating that the muscle glycogen reserves of the rats decreased after swimming. Compared with other groups, the Icariin-Zinc complex can reduce the level of glycogen in the muscles, indicating that it can increase the utilization efficiency of glycogen in muscles. Compared with the static control and exercise control groups, the testicular weight of rats in the administration groups increased slightly. The Icariin-Zinc complex increased the testicular weight, indicating that the function of the reproductive system was improved to some extent. Conclusion: Icariin-Zinc can significantly prolong the exhaustive swimming time, improve exercise ability, and increase the plasma testosterone level (which is beneficial for improving the reproductive ability of male rats). Moreover, the beneficial effect of Icariin-Zinc on the glycogen content, testis index, and other reproductive system glands is dose-dependent.

Exosomal miR-186 derived from BMSCs promote osteogenesis through hippo signaling pathway in postmenopausal osteoporosis.

BACKGROUND: Postmenopausal osteoporosis (PMO) that results from estrogen withdrawal is the most common primary osteoporosis among older women. However, little is known about the mechanism of PMO, and effective treatment of PMO is limited. METHODS: We used real-time polymerase chain reaction (qPCR), Western blotting, and RNA pull down to investigate the relationship between miR-186 and MOB Kinase Activator 1A (Mob1). Also, we investigated the effect of exosome in osteogenesis using alkaline phosphatase (ALP) staining. And hematoxylin eosin (HE) staining was used to verify the osteogenesis in PMO model. RESULTS: Exosomal miR-186 plays an important role in bone formation. The results of miRNA-seq and q-PCR showed that miR-186 was upregulated in a PMO + Exo treatment group. Results of RNA-pull down and luciferase reporter assays verified interactions between miR-186 and Mob1. We also verified the Hippo signaling pathway plays an important role in osteogenesis. CONCLUSIONS: We concluded that exosomes derived from human bone marrow mesenchymal stem cells (hBMSCs) can transfer miR-186 to promote osteogenesis in ovariectomy (OVX) rats through the Hippo signaling pathway.

Intra-Articular Injection of Umbilical Cord Mesenchymal Stem Cells Loaded With Graphene Oxide Granular Lubrication Ameliorates Inflammatory Responses and Osteoporosis of the Subchondral Bone in Rabbits of Modified Papain-Induced Osteoarthritis.

Aim: This study is to investigate the effects of umbilical cord mesenchymal stem cells (UCMSCs) loaded with the graphene oxide (GO) granular lubrication on ameliorating inflammatory responses and osteoporosis of the subchondral bone in knee osteoarthritis (KOA) animal models. Methods: The KOA animal models were established using modified papain joint injection. 24 male New Zealand rabbits were classified into the blank control group, GO group, UCMSCs group, and GO + UCMSCs group, respectively. The concentration in serum and articular fluid nitric oxide (NO), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), type II collagen (COL-II), and glycosaminoglycan (GAG) was detected using ELISA, followed by the dissection of femoral condyles and staining of HE and Micro-CT for observation via the microscope. Results: GO granular lubrication and UCMSCs repaired the KOA animal models. NO, IL-6, TNF-α, GAG, and COL-II showed optimal improvement performance in the GO + UCMSCs group, with statistical significance in contrast to the blank group (P <0.01). Whereas, there was a great difference in levels of inflammatory factors in serum and joint fluid. Micro-CT scan results revealed the greatest efficacy of the GO + UCMSCs group in improving joint surface damage and subchondral bone osteoporosis. HE staining pathology for femoral condyles revealed that the cartilage repair effect in GO + UCMSCs, UCMSCs, GO, and blank groups were graded down. Conclusion: UCMSCs loaded with graphene oxide granular lubrication can promote the secretion of chondrocytes, reduce the level of joint inflammation, ameliorate osteoporosis of the subchondral bone, and facilitate cartilage repair.

Effects of umbilical cord mesenchymal stem cells loaded with graphene oxide granular lubrication on cytokine levels in animal models of knee osteoarthritis.

BACKGROUND: The aim of this study was to use umbilical cord mesenchymal stem cells (UCMSCs) loaded with graphene oxide (GO) granular lubricant to treat knee osteoarthritis (KOA) animal models and to analyze their effect on cytokine levels in the articular cavity. METHODS: Twenty-four New Zealand rabbit models of KOA were established by the modified Hulth and cartilage injury method, and they were assigned to the blank group, the GO group, the UCMSC group, and the GO + UCMSC group, each group containing six animal models. The GO and UCMSC groups were treated by a single intra-articular injection. The treatment was started one month after surgical modeling, and the observation period was eight weeks. The expression levels of nitric oxide (NO), interleukin-6 (IL-6), tumour necrosis factor-α (TNF-α), glycosaminoglycan (GAG), and collagen-II (COL-II) in serum and articular fluid after treatment were compared to analyze the efficacy. RESULTS: The GO granular lubricant caused no significant improvement in the intra-articular environment of the knee joint, and UCMSCs caused a certain degree of improvement in the inflammatory environment. The improvement results of NO, IL-6, TNF-α, GAG, and COL-II were the best in the GO + UCMSC group, but the improvement results of inflammatory cytokine levels in serum and articular fluid were not consistent, especially the differences in NO, IL-6, and TNF-α were greater. CONCLUSION: UCMSCs loaded with the GO granular lubricant can reduce the inflammatory level and improve the level of biochemical environment in the articular cavity, and thus promote cartilage repair.

Engineering 3D functional tissue constructs using self-assembling cell-laden microniches.

Tissue engineering using traditional size fixed scaffolds and injectable biomaterials are faced with many limitations due to the difficulties of producing macroscopic functional tissues. In this study, 3D functional tissue constructs were developed by inducing self-assembly of microniches, which were cell-laden gelatin microcryogels. During self-assembly, the accumulation of extracellular matrix (ECM) components was found to strengthen cell-cell and cell-ECM interactions, leading to the construction of a 'native' microenvironment that better preserved cell viability and functions. MSCs grown in self-assembled constructs showed increased maintenance of stemness, reduced senescence and improved paracrine activity compared with cells grown in individual microniches without self-assembly. As an example of applying the self-assembled constructs in tissue regeneration, the constructs were used to induce in vivo articular cartilage repair and successfully regenerated hyaline-like cartilage tissue in the absence of other extrinsic factors. This unique approach of developing self-assembled 3D functional constructs holds great promise for the generation of tissue engineered organoids and repair of challenging tissue defects. STATEMENT OF SIGNIFICANCE: We developed 3D functional tissue constructs using a unique gelatin-based microscopic hydrogel (microcryogels). Mesenchymal stem cells (MSCs) were loaded into gelatin microcryogels to form microscopic cell-laden units (microniches), which were induced to undergo self-assembly using a specially designed 3D printed frame. Extracellular matrix accumulation among the microniches resulted in self-assembled macroscopic constructs with superior ability to maintain the phenotypic characteristics and stemness of MSCs, together with the suppression of senescence and enhanced paracrine function. As an example of application in tissue regeneration, the self-assembled constructs were shown to successfully repair articular cartilage defects without any other supplements. This unique strategy for developing 3D functional tissue constructs allows the optimisation of stem cell functions and construction of biomimetic tissue organoids.

Intra-articular Injection of Cell-laden 3D Microcryogels Empower Low-dose Cell Therapy for Osteoarthritis in a Rat Model.

Intra-articular injection of mesenchymal stem cells (MSCs) in an osteoarthritic joint can help slow down cartilage destruction. However, cell survival and the efficiency of repair are generally low due to mechanical damage during injection and a high rate of cell loss. We, thus, investigated an improved strategy for cell delivery to an osteoarthritic joint through the use of three-dimensional (3D) microcryogels. MSCs were seeded into 3D microcryogels. The viability and proliferation of MSCs in microcryogels were determined over 5 d, and the phenotype of MSCs was confirmed through trilineage differentiation tests and flow cytometry. In Sprague Dawley rats with induced osteoarthritis (OA) of the knee joint, a single injection was made with the following groups: saline control, low-dose free MSCs (1 × 105 cells), high-dose free MSCs (1 × 106 cells), and microcryogels + MSCs (1 × 105 cells). Cartilage degeneration was evaluated by macroscopic examination, micro-computed tomographic analysis, and histology. MSCs grown in microcryogels exhibited optimal viability and proliferation at 3 d with stable maintenance of phenotype in vitro. Microcryogels seeded with MSCs were, therefore, primed for 3 d before being used for in vivo experiments. At 4 and 8 wk, the microcryogels + MSCs and high-dose free MSC groups had significantly higher International Cartilage Repair Society macroscopic scores, histological evidence of more proteoglycan deposition and less cartilage loss accompanied by a lower Mankin score, and minimal radiographic evidence of osteoarthritic changes in the joint compared to the other two groups. In conclusion, intra-articular injection of cell-laden 3D microcryogels containing a low dose of MSCs can achieve similar effects as a high dose of free MSCs for OA in a rat model. Primed MSCs in 3D microcryogels can be considered as an improved delivery strategy for cell therapy in treating OA that minimizes cell dose while retaining therapeutic efficacy.

Repair of osteochondral defect using icariin-conditioned serum combined with chitosan in rabbit knees.

BACKGROUND: Osteochondral defects caused by an acute traumatic injury or articular degeneration remains difficult to be manipulated. Repair of articular defects is still a great challenge for both tissue engineers and orthopedic surgeons. Therefore, combination of biomaterials with cartilage promotive drugs is well worth being developed to support the regeneration of both cartilage and subchondral bone. METHODS: Rabbits undergoing osteochondral defect surgery were intrarticularly injected with icariin-conditioned serum (ICS), chitosan (CSSH) and combination of ICS with CSSH, respectively. Gait analysis was performed using VICON motion capture system. ICRS score and immunohistochemical (IHC) analysis including H&E, Safranin O, toluidine blue and collagen II staining was employed to evaluate macroscopic cartilage regeneration and determine the morphologic repair of cartilage. RESULTS: Rabbits with the treatment of ICS or CSSH alone showed mild improvement in hopping time and range of joint angles while ICS-CSSH group exhibited longer jumping time and larger range of joint angles. In addition, femoral condyle in ICS-CSSH rabbits could be seen with more native cartilage and subchondral bone regeneration in both macroscopic observation and IHC analysis. CONCLUSION: ICS combined with CSSH could promote the repair of osteochondral defect in rabbit knees. Combination of biomaterials with cartilage promotive drugs may ultimately have profound implications in the management of cartilage defect.

Medical exercise therapy alone versus arthroscopic partial meniscectomy followed by medical exercise therapy for degenerative meniscal tear: a systematic review and meta-analysis of randomized controlled trials.

OBJECTIVE: To explore if medical exercise therapy (MET) alone is comparable to arthroscopic partial meniscectomy (APM) followed by MET for knee pain, activity level, and physical function in middle-aged patients with degenerative meniscal tear (DMT) by a systematic review and meta-analysis of randomized controlled trials (RCTs). METHOD: A systematic search of electronic databases (PubMed, the Cochrane Library, Embase, and Web of Science) was conducted to retrieve RCTs comparing MET+APM with MET alone for DMT. Risk of bias of the studies was evaluated. Outcomes assessed were pain relief, physical function, and activity level. RESULTS: A total of 6 RCTs containing 879 patients were included. After pooling the data of 5 researches, we found small significant differences support the APM + MET group for pain control assessed by Knee injury and Osteoarthritis Outcome Score (KOOS) at 2 to 3 months (p = 0.004) and at 6 months (p = 0.04). And there were statistically improvements in APM + MET at 6 months compared with MET alone when changing measurement to visual analog scale (VAS) (p = 0.0003). Our analysis also found small significant differences favor the APM followed by MET group for physical function both at 2 to 3 months (p = 0.01, KOOS and Western Ontario and McMaster Universities Osteoarthritis Index, WOMAC; and P = 0.40, Lysholm Knee Scoring Scale) and at 6 months (p = 0.01, KOOS and WOMAC). CONCLUSION: We found favorable results of APM + MET up to 6 months for pain control and physical function. However, there were no differences at longer follow-up. The clinical applicability of APM + MET compared with MET should be interpreted carefully, and the potential of MET to treat DMT should be valued.

Intra-articular delivery of umbilical cord-derived mesenchymal stem cells temporarily retard the progression of osteoarthritis in a rat model.

AIM: Mesenchymal stem cell (MSC)-based therapy is being explored in treating osteoarthritis (OA). Human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) are least reported. In this study, we investigated the effects of single intra-articular injections of hUC-MSCs on a rat OA model. METHOD: hUC-MSCs were isolated from the Wharton's jelly of the human umbilical cord and identified. Eighteen Sprague-Dawley rats were used for the OA model. All rats were divided into 3 groups: hyaluronic acid (HA)+MSCs (n = 6), HA (n = 6), and control group (n = 6). One by 106 hUC-MSCs in 100 µL HA, 100 µL HA or 100 µL saline were injected into the knee joint 4 weeks post-surgery as a single dose. Cartilage degeneration was evaluated at 6 and 12 weeks after treatment with macroscopic examination, micro-computed tomography analysis, behavioral analysis, and histology. RESULTS: At 6 weeks, the HA + MSCs group had a significantly better International Cartilage Repair Society score in the femoral condyle compared to the HA and control groups. Histological analysis also showed more proteoglycan and less cartilage loss, with lower modified Mankin score in the HA + MSCs group. However, at 12 weeks there were no significant differences between groups from macroscopic examination and histological analysis. Subchondral bone sclerosis of the medial femoral condyle and behavioral tests showed no significant differences between groups at 6 and 12 weeks. CONCLUSION: These findings indicate that single injection of hUC-MSCs can have temporary effects on decelerating the progression of cartilage degeneration in OA rats, but may not inhibit OA progression in the long-term.