Stem cell-based therapeutic strategies for rotator cuff tendinopathy.

Rotator cuff tendinopathy is a common musculoskeletal disorder that imposes significant health and economic burden. Stem cell therapy has brought hope for tendon healing in patients with final stage rotator cuff tendinopathy. Some clinical trials have confirmed the effectiveness of stem cell therapy for rotator cuff tendinopathy, but its application has not been promoted and approved. There are still many issues that should be solved prior to using stem cell therapy in clinical applications. The optimal source and dose of stem cells for rotator cuff tendinopathy should be determined. We also proposed novel prospective approaches that can overcome cell population heterogeneity and standardize patient types for stem cell applications. The translational potential of this article: This review explores the optimal sources of stem cells for rotator cuff tendinopathy and the principles for selecting stem cell dosages. Key strategies are provided for stem cell population standardization and recipient selection.

Arthroscopic Superior Capsular Reconstruction for Massive Irreparable Rotator Cuff Tears Results in Significant Improvements in Patient Reported Outcomes and Range of Motion: A Systematic Review.

Purpose: The purposes of this study were to evaluate the clinical outcomes (with the minimum mean follow-up period of 2 years) of arthroscopic superior capsular reconstruction (ASCR) using different grafts for massive irreparable rotator cuff tears (MIRCTs) and to explore whether margin convergence in ASCR affects range of motion (ROM) outcomes. Methods: This systematic review was registered in PROSPERO and was then conducted following PRISMA guidelines by searching the databases: MEDLINE, EMBASE, Web of Science, and Cochrane Library database before April 2021. These literature searches investigating the clinical outcomes of ASCR were included. The methodological quality of included studies was assessed using the MINORS criteria. The data, including margin convergence, patient-reported outcome scores, range of motion, and complications, were extracted and analyzed. The minimal clinically important differences (MCID) criteria was used to define clinical significance. Results: 15 studies met the inclusion criteria. All studies reported statistically significant improvements in visual analog scale scores (range: 2.07 to 7.1) and American Shoulder and Elbow Surgeons scores (range: 18.1 to 58). Significant improvements of Constant scores were noted in 4 of 5 reporting studies (mean improvement ranged from 14.64 to 50.79). Active forward flexion/elevation (11 studies), active abduction (4 studies), and active external rotation (8 studies) displayed improvements in all reporting studies, with mean changes ranging from 12 to 73.68, 19 to 89.21, and 1 to 24.74, respectively. The mean change of postoperative acromiohumeral distance ranged from -0.86 mm to 3.2 mm in 9 studies. The postoperative complication rate of ASCR ranged from 4.5% to 47.6%. The anterior margin convergence in SCR was associated with a relatively poor improvement in active external rotation. Conclusions: ASCR contributes to significant improvements in patient-reported clinical outcomes and ROM at follow-up after a mean of more than two years, emerging as a viable option for patients with MIRCTs. The anterior margin convergence should be prudently chosen, especially in ASCR using fascia lata autograft, on account of the probable restriction on postoperative active external rotation. Level of Evidence: Level IV, systematic review of Level III and IV studies.

Optimizing magnetic functionalization conditions for efficient preparation of magnetic biochar and adsorption of Pb(II) from aqueous solution.

Recoverable magnetic biochar has great potential for treating wastewater contaminants such as Pb(II). However, whether magnetic modification could enhance metal adsorption efficiency is currently contradictory in the literature mainly due to the differences in selecting various magnetic functionalization conditions. Considering this gap in knowledge, the effects of magnetic functionalization method (impregnation and precipitation), concentration of precursor iron solution (0.01-1 M), and pyrolysis temperature (300-700 °C) on the characteristics and Pb(II) adsorption capacity of biochar were systematically investigated in this paper. Results indicated that Fe3O4 was the main product for magnetic biochars synthesized using the impregnation (denoted as FWFe(3)) and precipitation methods (denoted as FWFe(2)). Magnetic functionalization resulted in remarkably increased pH and more negative zeta potential for FWFe(2) samples, whereas FWFe(3) samples showed the opposite trends. The adsorption of Pb(II) on different biochars fitted the pseudo-second order model and the Langmuir model. The maximum adsorption capacity was 817.64 mg/g for FWFe(2)1M700C (precipitation by 1 M of Fe(II)/Fe(III), pyrolysis at 700 °C), outperforming FWFe(3) and pristine biochar samples by around 5-13 times. Mechanism study indicated that the adsorption mainly involved electrostatic attraction, ion exchange, co-precipitation, and complexation. Pb(II) adsorption capacity was strongly dependent on the alkali pH of biochar. However, this efficiency was less affected by biochar surface area and its morphology. The higher pH of FWFe(2) samples not only led to an increased surface charge for stronger electrostatic attraction and ion exchange but also favored the formation of co-precipitates. By contrast, FWFe(3) samples showed a decreased adsorption capacity for Pb(II) with increased concentration of embedded iron. Overall, magnetic biochar, prepared using precipitation followed by high-temperature pyrolysis (such as, FWFe(2)1M700C), can be a promising adsorbent for Pb(II) adsorption from wastewater.

An Off-the-Shelf Tissue Engineered Cartilage Composed of Optimally Sized Pellets of Cartilage Progenitor/Stem Cells.

Articular cartilage focal lesion remains an intractable challenge in sports medicine, and autologous chondrocytes' implantation (ACI) is one of the most commonly utilized treatment modality for this ailment. However, the current ACI technique requires two surgical steps which increases patients' morbidity and incurs additional medical costs. In the present study, we developed a one-step cryopreserved off-the-shelf ACI tissue-engineered (TE) cartilage by seeding pellets of spheroidal cartilage stem/progenitor cells (CSPCs) on a silk scaffold. The pellets were developed through a hanging-drop method, and the incubation time of 1 day could efficiently produce spheroidal pellets without any adverse influence on the cell activity. The pellet size was also optimized. Under chondrogenic induction, pellets consisting of 40 000 CSPCs were found to exhibit the most abundant cartilage matrix deposition and the highest mRNA expression levels of SOX9, aggrecan, and COL2A1, as compared with pellets consisting of 10 000, 100 000, or 200 000 CSPCs. Scaffolds seeded with CSPCs pellets containing 40 000 cells could be preserved in liquid nitrogen with the viability, migration, and chondrogenic ability remaining unaffected for as long as 3 months. When implanted in a rat trochlear cartilage defect model for 3 months, the ready-to-use, cryopreserved TE cartilage yielded fully cartilage reconstruction, which was comparable with the uncryopreserved control. Hence, our study provided preliminary data that our off-the-shell TE cartilage with optimally sized CSPCs pellets seeded within silk scaffolds exhibited strong cartilage repair capacity, which provided a convenient and promising one-step surgical approach to ACI.

Effects of food and grapefruit juice on single-dose pharmacokinetics of blonanserin in healthy Chinese subjects.

PURPOSE: The purpose of this study was to investigate the potential effects of a meal and grapefruit juice on the pharmacokinetics of blonanserin and its metabolite N-desethyl blonanserin in healthy Chinese volunteers. METHODS: This was a single-centre, open-label, fixed-sequence study, where 12 healthy Chinese volunteers received a single dose of 8 mg blonanserin after an overnight fast in period 1 (reference), a high-fat meal during period 2 and with co-administration of 250 mL of grapefruit juice in period 3. The washout period was 7 days. Series of plasma samples were collected after each dose to determine concentrations of blonanserin and its metabolite N-desethyl blonanserin using liquid chromatography-tandem mass spectrometry. Pharmacokinetic parameters were estimated by non-compartmental analysis and compared between periods by standard average bioequivalence ANOVA. Adverse events were monitored throughout the study. RESULTS: All subjects completed the study. High-fat meals significantly increased blonanserin exposure (AUCt) 2.58-fold (90% CI 2.21, 3.02), relative to the reference period. Co-administration of blonanserin with grapefruit juice remarkably prolonged elimination half-life of blonanserin (from 9.7 to 21.4 h) and significantly increased exposures to blonanserin and N-desethyl blonanserin by 5.82-fold (90% CI 4.57, 7.42) and 1.81-fold (90% CI 1.65, 1.98), respectively. CONCLUSIONS: These results suggested that blonanserin was largely metabolised in the intestinal tract before becoming systemically available, and both food and grapefruit juice enhanced exposure to blonanserin and N-desethyl blonanserin. Grapefruit juice increased bioavailability and may have reduced systemic clearance of blonanserin. Further intestinal CYP3A4 and hepatic CYP3A4 might be postulated to explain the delayed elimination of blonanserin. Dose adjustment of blonanserin is needed on the basis of co-intake of known strong CYP3A4 inhibitor. Patients taking high-dose blonanserin also need to be cautious about the ingestion of grapefruit juice.

Pharmacokinetic Properties of Peramivir After Single and Multiple Intravenous Infusions in Healthy Chinese Volunteers.

BACKGROUND AND OBJECTIVES: Peramivir, an antiviral agent for intravenous administration, is used to treat progressive influenza in patients with serious complications. The present study was designed to determine the pharmacokinetics of single and multiple intravenous infusions of peramivir in healthy Chinese subjects. METHODS: Single (150, 300 and 600 mg) and multiple (600 mg) doses of peramivir were intravenously administered to 12 healthy Chinese subjects. There was a 7-day washout period between dosing periods. Blood samples were collected in heparinized tubes at various times. Plasma peramivir and urine peramivir concentrations were measured using a high-performance liquid chromatography-tandem mass spectrometry method. RESULTS: Following single doses of peramivir (150, 300 and 600 mg), the maximum concentration (C max) values were 12,416 ± 3078, 23,147 ± 3668 and 44,113 ± 3787 µg/L, respectively, and the area under the plasma concentration-time curve (AUC) from 0 h to infinity post-dose (AUC∞) values were 24.68 ± 6.48, 47.33 ± 9.22 and 92.43 ± 12.72 mg·h/L, respectively. C max, AUC from 0 to 36 h (AUC0-36) and AUC∞ of peramivir increased proportionally with the dose, and no trend towards accumulation after multiple doses was observed. About 65 % of the peramivir was excreted unchanged in the urine within the first 24 h. CONCLUSIONS: Peramivir pharmacokinetics were dose proportional with increasing doses, with no accumulation after multiple dosing. Peramivir was generally well tolerated, and no serious adverse events occurred.