Intra-articular Histone Deacetylase Inhibitor Microcarrier Delivery to Reduce Osteoarthritis.

The histone deacetylase inhibitor (HDACi) was a milestone in the treatment of refractory T-cell lymphoma. However, the beneficial effects of HDACi have not been appreciated in osteoarthritis (OA). Herein, we implemented a microcarrier system because of the outstanding advantages of controlled and sustained release, biodegradability, and biocompatibility. The poly(d,l-lactide-co-glycolide) (PLGA) microcapsules have a regulated and sustained release profile with a reduced initial burst release, which can improve the encapsulation efficiency of the Chidamide. The emulsion solvent evaporation strategy was used to encapsulate Chidamide in PLGA microcapsules. The encapsulation of Chidamide was established by UV-vis spectra and scanning electron microscopy. Additionally, the inhibition of Tnnt3 and immune stimulation by Chidamide helped to inhibit cartilage destruction and prevent articular cartilage degeneration. Based on the results, the Chidamide in PLGA microcapsules provides a transformative therapeutic strategy for the treatment of osteoarthritis patients to relieve symptoms and protect against cartilage degeneration.

Quadriceps-sparing versus traditional medial parapatellar approaches for total knee arthroplasty: a meta-analysis.

BACKGROUND: There is still controversy regarding whether Quadriceps-sparing (QS) approach for total knee arthroplasty (TKA) lead to better earlier recovery as well as compromising low limb alignment and prosthesis position compared with conventional medial parapatellar (MP) approach. To overcome the shortcomings and inaccuracies of single studies, the clinical outcomes and radiographic assessments of QS approach and MP approach were evaluated through meta-analysis. METHODS: We performed this meta-analysis according to the Preferred Reporting Items for Systematic Reviews and Meta-analysis guidelines. A literature search was conducted in the PubMed, EMBase, Cochrane Collaboration Library and Web of Science databases. Our search strategy followed the requirements of the Cochrane Library Handbook. The study selection, data extraction and assessment of methodological quality were independently completed by four authors. And subgroup analysis and publication bias were also performed in the study. RESULTS: Eight prospective randomized controlled trials (RCTs) and eight retrospective studies were identified. Overall meta-analysis and subgroup meta-analysis of RCTs identified the QS approach mainly was associated with increased Knee Society function score beyond 24 months postoperatively (weighted mean difference [WMD] 1.78, P = 0.0004) (WMD 1.86, P = 0.0002), and improved range of motion 1-2 weeks postoperatively (WMD 5.84, P < 0.00001) (WMD 4.87, P = 0.002). Besides, lower visual analogue scale on postoperative day 1 (WMD -0.91, P = 0.02), shorter hospital stay (WMD -0.88, P = 0.02) and shorter incision (extension) (WMD -4.62, P < 0.00001) were indicated in overall meta-analysis. However, surgical and tourniquet time was significantly longer in QS group by both overall and subgroup meta-analysis. CONCLUSIONS: QS approach may accelerate early recovery without increasing the risk of malalignment of low limb and malposition of prosthesis.

The roles of metabolic thermogenesis in body fat regulation in striped hamsters fed high-fat diet at different temperatures.

The metabolic thermogenesis plays important roles in thermoregulation, and it may be also involved in body fat regulation. The thermogenesis of brown adipose tissue (BAT) is largely affected by ambient temperature, but it is unclear if the roles in body fat regulation are dependent on the temperature. In the present study, uncoupling protein 1 (ucp1)-based BAT thermogenesis, energy budget and body fat content were examined in the striped hamsters fed high fat diet (HF) at cold (5°C) and warm (30°C) temperatures. The effect of 2, 4-dinitrophenol (DNP), a chemical uncoupler, on body fat was also examined. The striped hamsters showed a notable increase in body fat following the HF feeding at 21°C. The increased body fat was markedly elevated at 30°C, but was significantly attenuated at 5°C compared to that at 21°C. The hamsters significantly increased energy intake at 5°C, but consumed less food at 30°C relative to those at 21°C. Metabolic thermogenesis, indicated by basal metabolic rate, UCP1 expression and/or serum triiodothyronine levels, significantly increased at 5°C, but decreased at 30°C compared to that at 21°C. A significant decrease in body fat content was observed in DNP-treated hamsters relative to the controls. These findings suggest that the roles of metabolic thermogenesis in body fat regulation largely depend on ambient temperature. The cold-induced enhancement of BAT thermogenesis may contribute the decreased body fat, resulting in a lean mass. Instead, the attenuation of BAT thermogenesis at the warm may result in notable obesity.

Risk of total/subtotal meniscectomy for respective medial and lateral meniscus injury: correlation with tear type, duration of complaint, age, gender and ACL rupture in 6034 Asian patients.

BACKGROUND: To evaluate the risk factor associated with total or subtotal meniscectomy for respective medial and lateral meniscus injury. METHODS: The data of all the meniscus injured patients undergoing arthroscopy in our institute between January 15th, 2000 and December 31st, 2008 was collected and 6034 patients with 7241 injured menisci met the inclusion criteria. The mean patient age was 33.6 ± 14.9 years and there were 4785 males and 2456 females with 3568 medial and 3673 lateral menisci. The decision tree approach was applied to investigate the correlation of the tear type, the duration of complaint, age, gender, ACL rupture and total/subtotal meniscectomy for respective medial and lateral meniscus. RESULTS: The tear type was associated with both medial (χ2 = 70.901, P < 0.001) and lateral (χ2 = 268.019, P < 0.001) total/subtotal meniscectomy. The strongest risk of total/subtotal meniscectomy of both medial and lateral meniscus tear was shown for the complex tear followed by the longitudinal, oblique, horizontal and radial tear of the medial meniscus and followed by horizontal, longitudinal, radial and oblique tear of the lateral meniscus. The risk of total/subtotal medial meniscectomy was significantly elevated for the patients with complex tear and the age of ≤40 years old (χ2 = 21.028, P < 0.001) and those with the oblique, horizontal or radial tear accompanied by ACL rupture (χ2 = 6.631, P = 0.01). Besides, the duration of complaint was also associated with total/subtotal meniscectomy of the medial longitudinal tear with ACL rupture (χ2 = 17.155, P < 0.001). On the other side, the risk of total/subtotal lateral meniscectomy was significantly elevated for the complex tear of the female patients (χ2 = 5.877, P = 0.015) with no ACL rupture (χ2 = 50.501, P < 0.001). The ACL rupture was associated with a decreased risk of total/subtotal meniscectomy for all the types of the lateral meniscus (complex: χ2 = 50.501, P < 0.001; horizontal: χ2 = 20.897, P < 0.001; oblique: χ2 = 27.413, P < 0.001; longitudinal and radial: χ2 = 110.85, P < 0.001). CONCLUSION: Analyzing data from a big sample available in an Asian patient database, we found different risk factors associated with total/subtotal meniscectomy for respective medial and lateral meniscus. Identifying patients at high risk for total/subtotal meniscectomy may allow for interventions after meniscus injury.

Plasticity in gastrointestinal morphology and enzyme activity in lactating striped hamsters (Cricetulus barabensis).

In small mammals, marked phenotypic plasticity of digestive physiology has been shown to make it easier for them to cope with energetically stressful periods, such as lactation. It has been proposed that the capacity of the gut to digest and absorb food is not the limiting factor to sustained energy intake (SusEI) during peak lactation. In this study, plasticity in energy intake and gastrointestinal morphology was examined in striped hamsters at different stages of reproduction and when raising litters of different sizes. Mechanisms associated with digestive enzymes and neuroendocrine hormones underpinning the plasticity were also examined. Females significantly increased energy intake, digestibility, digestive tract mass and the activity of stomach pepsin and small intestine maltase, sucrase and aminopeptidase in peak lactation compared with the non-productive and post-lactating periods. Further, females raising large litters significantly increased energy intake, digestibility, gastrointestinal mass and activity of digestive enzymes, and weaned heavier offspring compared with those nursing small and medium litters, indicating that the significant plasticity of digestive physiology increased reproductive performance. Agouti-related protein (AgRP) mRNA expression in the hypothalamus was up-regulated significantly in females raising large litters relative to those raising small litters. Serum leptin levels, and mRNA expression of hypothalamus neuropeptide Y (NPY) and the anorexigenic neuropeptides pro-opiomelanocortin (POMC) and cocaine- and amphetamine-regulated transcript (CART) did not differ among females raising small, medium and large litters. Leptin levels in lactation may only reflect a state of energy balance rather than being the prime driver of hyperphagia. Some hypothalamic neuropeptides, such as NPY, POMC and CART, may be involved in the limits to the SusEI during lactation.

Intraoperative anthropomorphic study of anterior femoral condyles compared with sizing of femoral arthroplasty.

PURPOSE: The present study was designed to compare the dimensions of the anterior femoral condyle with those of the anterior component flange using intraoperative morphological data. METHODS: Overall, 1227 knees in 962 patients were included in this study. The height of the anterior lateral/medial condylar height (ALCH/AMCH) was measured and compared between men and women. These morphological data were compared with the dimensions of the chosen component for each patient. The lateral/medial anterior femoral offset was calculated, and the over-/understuffing rates were compared between men and women. RESULTS: The median ALCH in men was 8.5 mm (6.5, 10.0 mm) versus 7.0 mm (6.0, 9.0 mm) in women. The median AMCH in men was 4.0 mm (2.5, 6.0 mm) versus 3.5 mm (2.5, 6.0 mm) in women. There was a significant difference between the genders with respect to ALCH (p < 0.05). When the dimensions of the component were compared with those of the native knee, the anterior lateral flange height was smaller than the native knees (1.3 mm in male, 0.7 mm in female), but the anterior medial flange height was larger than the corresponding condyle (1.8 mm in male, 1.8 mm in female). A significant difference was observed between the genders with respect to the ideal fit rate of ALCH (p < 0.01). CONCLUSION: The results demonstrate that gender differences exist in the anterior lateral condyles of knees. The anterior flange of component is not designed to precisely reproduce normal trochlear anatomy. LEVEL OF EVIDENCE: II.

Food restriction attenuates oxidative stress in brown adipose tissue of striped hamsters acclimated to a warm temperature.

It has been suggested that the up-regulation of uncoupling proteins (UCPs) decreases reactive oxygen species (ROS) production, in which case there should be a negative relationship between UCPs expression and ROS levels. In this study, the effects of temperature and food restriction on ROS levels and metabolic rate, UCP1 mRNA expression and antioxidant levels were examined in the brown adipose tissue (BAT) of the striped hamsters (Cricetulus barabensis). The metabolic rate and food intake of hamsters which had been restricted to 80% of ad libitum food intake, and acclimated to a warm temperature (30°C), decreased significantly compared to a control group. Hydrogen peroxide (H2O2) levels were 42.9% lower in food restricted hamsters than in the control. Malonadialdehyde (MDA) levels of hamsters acclimated to 30°C that were fed ad libitum were significantly higher than those of the control group, but 60.1% lower than hamsters that had been acclimated to the same temperature but subject to food restriction. There were significantly positive correlations between H2O2 and, MDA levels, catalase activity, and total antioxidant capacity. Cytochrome c oxidase activity and UCP1 mRNA expression significantly decreased in food restricted hamsters compared to the control. These results suggest that warmer temperatures increase oxidative stress in BAT by causing the down-regulation of UCP1 expression and decreased antioxidant activity, but food restriction may attenuate the effects.

Optimal patellar alignment with minimally invasive approaches in total knee arthroplasty after a minimum five year follow-up.

PURPOSE: Patellofemoral syndrome is still a common complication after total knee arthroplasty (TKA). However, the effects of specific surgical approaches on patellar tracking and alignment remain incompletely understood. In this study, we compared patellar alignment in patients who underwent TKA via three different techniques. METHODS: A total of 96 patients who completed a minimum follow-up of five years were involved in three groups: 30 patients were treated with the traditional medial parapatellar approach (MPP group), 35 patients were treated with the mini-medial parapatellar approach (MMP group) and 31 were treated with a quadriceps-sparing approach (QS group). Radiographic data for patellar alignment and clinical results were compared. RESULTS: Patellar tilt and patellar displacement at the final follow-up evaluation differed significantly among the three groups [P < 0.01, analysis of variance (ANOVA)]. The MMP and QS groups exhibited more proper patellar alignment than the MPP group. The clinical results did not differ significantly among the groups (P > 0.05, ANOVA). In addition, there were no correlations between postoperative patellar alignment and clinical scores. CONCLUSIONS: The results of this study indicate that TKA performed using minimally invasive approaches yields superior patellar alignment compared to the traditional MPP approach.

Exogenous IFN-beta regulates the RANKL-c-Fos-IFN-beta signaling pathway in the collagen antibody-induced arthritis model.

BACKGROUND: Although a variety of drugs have been used to treat the symptoms of rheumatoid arthritis (RA), none of them are able to cure the disease. Interferon ß (IFN-ß) has pleiotropic effects on RA, but whether it can be used to treat RA remains globally controversial. Thus, in this study we tested the effects of IFN-ß on RA patients and on collagen antibody-induced arthritis (CAIA) model mice. METHODS: The cytokine and auto-antibody expression profiles in the serum and synovial fluid (SF) from RA patients were assessed using enzyme-linked immunosorbent assay (ELISA) and compared with the results from osteoarthritis (OA) patients. Exogenous IFN-ß was administered to RA patients and CAIA model mice, and the therapeutic effects were evaluated. Endogenous IFN-ß expression in the joint bones of CAIA model mice was evaluated by quantitative real-time PCR (qRT-PCR). The effects of exogenous IFN-ß on CAIA model mice were assessed using a clinical scoring system, hematoxylin eosin and safranin-O with fast green counterstain histology, molybdenum target X-ray, and tartrate-resistant acid phosphatase (TRAP) staining. The RANKL-RANK signaling pathway was analyzed using qRT-PCR. The RAW 264.7 cell line was differentiated into osteoclasts with RANKL stimulation and then treated with exogenous IFN-ß. RESULTS: The expression of inflammatory cytokines (IFN-γ, IL-17, MMP-3, and RANKL) and auto-antibodies (CII antibodies, RF-IgM, and anti-CCP/GPI) were significantly higher in RA compared with OA patients. After IFN-ß intervention, some clinical symptoms in RA patients were partially alleviated, and the expression of IFN-γ, IL-17, MMP-3, and OPG) returned to normal levels. In the CAIA model, the expression of endogenous IFN-ß in the joint bones was decreased. After IFN-ß administration, the arthritis scores were decreased; synovial inflammation, cartilage, and bone destruction were clearly attenuated; and the expression of c-Fos and NFATc1 were reduced, while RANKL and TRAF6 expression was unchanged. In addition, exogenous IFN-ß directly inhibited RANKL-induced osteoclastogenesis. CONCLUSIONS: Exogenous IFN-ß administration immunomodulates CAIA, may reduce joint inflammation and, perhaps more importantly, bone destruction by inhibiting the RANKL-c-Fos signaling pathway. Exogenous IFN-ß intervention should be selectively used on RA patients because it may only be useful for RA patients with low endogenous IFN-ß expression.

Computed tomography morphometric study of gender differences in osteoarthritis proximal tibias.

One hundred and thirty osteoarthritic knees(65 males, 65 females) from a Chinese population were measured by computed tomography for tibial mediolateral (ML), middle anteroposterior (AP), medial anteroposterior (MAP), lateral anteroposterior (LAP) dimensions and ML/AP aspect ratio. The ML/AP aspect ratio were classified into 3 groups based on AP dimensions(<48 mm, 48-52 mm, >52 mm) to compare the morphologic differences of proximal tibia between males and females. The mean ML, AP, MAP and LAP dimensions of proximal tibia showed significant differences for sex (P < .01). We found a progressively decreased in the ML/AP aspect ratio with an increasing AP dimension, and males have larger ML/AP aspect ratio than that of females under a given AP dimension (P < .01). This indicates that under a given AP dimension prosthesis, the tibial ML dimension have the potential to be undersized in males and to overhang in females. This study may provide important reference in designing proper gender-specific tibia prosthesis with different ML/AP aspect ratio for Chinese males and females.

Protein-spatiotemporal partition releasing gradient porous scaffolds and anti-inflammatory and antioxidant regulation remodel tissue engineered anisotropic meniscus.

Meniscus is a wedge-shaped fibrocartilaginous tissue, playing important roles in maintaining joint stability and function. Meniscus injuries are difficult to heal and frequently progress into structural breakdown, which then leads to osteoarthritis. Regeneration of heterogeneous tissue engineering meniscus (TEM) continues to be a scientific and translational challenge. The morphology, tissue architecture, mechanical strength, and functional applications of the cultivated TEMs have not been able to meet clinical needs, which may due to the negligent attention on the importance of microenvironment in vitro and in vivo. Herein, we combined the 3D (three-dimensional)-printed gradient porous scaffolds, spatiotemporal partition release of growth factors, and anti-inflammatory and anti-oxidant microenvironment regulation of Ac2-26 peptide to prepare a versatile meniscus composite scaffold with heterogeneous bionic structures, excellent biomechanical properties and anti-inflammatory and anti-oxidant effects. By observing the results of cell activity and differentiation, and biomechanics under anti-inflammatory and anti-oxidant microenvironments in vitro, we explored the effects of anti-inflammatory and anti-oxidant microenvironments on construction of regional and functional heterogeneous TEM via the growth process regulation, with a view to cultivating a high-quality of TEM from bench to bedside.

Meniscus transplantation using treated xenogeneic meniscal tissue: viability and chondroprotection study in rabbits.

PURPOSE: This was a preliminary study performed in vivo to evaluate the viability and the chondroprotective effects of irradiated deep-frozen xenogeneic meniscal tissue as a novel substitute for meniscus transplantation. METHODS: Medial meniscectomies were performed on the right knees of 48 New Zealand white rabbits. The inner one-third of pig meniscus was harvested and then irradiated and deeply frozen. The treated xenogeneic meniscal tissues were then transplanted to 24 right knees (Xeno group), whereas 24 other knees received meniscus allograft transplantations (Allo group). The left knees of the Xeno group and Allo group received meniscectomies (Meni group) and sham operations (Sham group), respectively. The rabbits were killed at weeks 6, 12, and 24 postoperatively. The newly formed structure of the implanted tissue and cartilage of the medial compartment of each group was assessed by gross and semiquantitative histologic analysis. RESULTS: After 24 weeks, the implanted xenogeneic meniscal tissue completely healed to the synovium and formed meniscus-like tissue. The chondrocyte-like cell infiltrated into the tissue with extracellular matrix including type II collagen and proteoglycans. The Xeno group showed significantly less cartilage degeneration than that of the Meni group in the medial tibial plateau at week 24 (P < .05). No significant difference was found between the Xeno group and the Allo group except for the meniscus-covered regions at week 24. From week 12 to week 24, almost no advanced cartilage degeneration was found in weight-bearing regions of the medial tibial plateau of the Xeno group. CONCLUSIONS: The treated xenogeneic meniscal tissue healed to the synovium with tissue regeneration and slowed down articular cartilage degeneration in the short-term. The chondroprotection of xenograft transplantation was similar to that of allograft transplantation. CLINICAL RELEVANCE: The treated xenogeneic meniscal tissue showed the potential for viability and slowed cartilage degeneration, but more studies are required for application in humans in the future.

Integrated Analysis of lncRNA and mRNA Expression Profiles Indicates Age-Related Changes in Meniscus.

Little has been known about the role of long non-coding RNA (lncRNA) involves in change of aged meniscus. Microarray analyses were performed to identify lncRNAs and mRNAs expression profiles of meniscus in young and aging adults and apple bioinformatics methods to analyse their potential roles. The differentially expressed (DE) lncRNAs and mRNAs were confirmed by qRT-PCR. A total of 1608 DE lncRNAs and 1809 DE mRNAs were identified. Functional and pathway enrichment analyses of all DE mRNAs showed that DE mRNAs were mainly involved in the TGF-beta, Wnt, Hippo, PI3K-Akt signaling pathway. The expressions of TNFRSF11B and BMP2 were significantly upregulated in aging group. LASSO logistic regression analysis of the DE lncRNAs revealed four lncRNAs (AC124312.5, HCG11, POC1B-AS1, and AP001011.1) that were associated with meniscus degradation. CNC analysis demonstrated that AP001011 inhibited the expression of TNFRSF11B and AC1243125 upregulated the expression of TNFRSF11B. CeRNA analysis suggested that POC1B-AS1 regulates the expression of BMP2 by sponging miR 130a-3p, miR136-5p, miR 18a-3p, and miR 608. Furthermore, subcellular localization and m6A modification sites prediction analysis of these four lncRNAs was performed. These data lay a foundation for extensive studies on the role of lncRNAs in change of aged meniscus.

Immunomodulatory PEG-CRGD Hydrogels Promote Chondrogenic Differentiation of PBMSCs.

Cartilage damage is a common injury. Currently, tissue engineering scaffolds with composite seed cells have emerged as a promising approach for cartilage repair. Polyethylene glycol (PEG) hydrogels are attractive tissue engineering scaffold materials as they have high water absorption capacity as well as nontoxic and nutrient transport properties. However, PEG is fundamentally bio-inert and lacks intrinsic cell adhesion capability, which is critical for the maintenance of cell function. Cell adhesion peptides are usually added to improve the cell adhesion capability of PEG-based hydrogels. The suitable cell adhesion peptide can not only improve cell adhesion capability, but also promote chondrogenesis and regulate the immune microenvironment. To improve the interactions between cells and PEG hydrogels, we designed cysteine-arginine-glycine-aspartic acid (CRGD), a cell adhesion peptide covalently cross-linked with PEG hydrogels by a Michael addition reaction, and explored the tissue-engineering hydrogels with immunomodulatory effects and promoted chondrogenic differentiation of mesenchymal stem cells (MSCs). The results indicated that CRGD improved the interaction between peripheral blood mesenchymal stem cells (PBMSCs) and PEG hydrogels. PEG hydrogels modified with 1 mM CRGD had the optimal capacity to promote chondrogenic differentiation, and CRGD could induce macrophage polarization towards the M2 phenotype to promote tissue regeneration and repair. PEG-CRGD hydrogels combined with PBMSCs have the potential to be suitable scaffolds for cartilage tissue engineering.

Study on feasibility of the partial meniscal allograft transplantation.

Since the meniscus is an important stabilizing structure of the knee joint and has a significant role in load-bearing and shock absorption, so the complete structural and functional reconstructions of the teared menisci should be done not only after partial meniscectomy but also post total meniscectomy. So far, animal experiments and good clinical practice have showed that TMAT after total meniscectomy has partially solved the problem of structural and functional reconstructions after total meniscectomy. However, partial meniscectomy will also lead to accelerated knee degeneration, and its proportion is much higher than that of patients with total meniscectomy. Herein, the feasibility of PMAT after partial meniscectomy was investigated for the first time by using the 40% posterior horn meniscectomy model of the medial meniscus in Beagle dogs, and also for the first time, TMAT group and the total meniscectomy group were used as control groups. Compared with the TMAT, the transcriptomics evaluation, scanning electron microscope observation, histological regeneration and structure, biomechanical property, inflammation environment, and the knee function post PMAT were more similar to that of normal meniscus was first reported. This study provides a PMAT scheme with clinical translational value for the complete structural and functional reconstruction of the patients with partial meniscectomy and fills the gap in the field of teared meniscus therapy on the basis of quite well clinical applications of the meniscus repair and the TMAT.

Kartogenin-Conjugated Double-Network Hydrogel Combined with Stem Cell Transplantation and Tracing for Cartilage Repair.

The effectiveness of existing tissue-engineering cartilage (TEC) is known to be hampered by weak integration of biocompatibility, biodegradation, mechanical strength, and microenvironment supplies. The strategy of hydrogel-based TEC holds considerable promise in circumventing these problems. Herein, a non-toxic, biodegradable, and mechanically optimized double-network (DN) hydrogel consisting of polyethylene glycol (PEG) and kartogenin (KGN)-conjugated chitosan (CHI) is constructed using a simple soaking strategy. This PEG-CHI-KGN DN hydrogel possesses favorable architectures, suitable mechanics, remarkable cellular affinity, and sustained KGN release, which can facilitate the cartilage-specific genes expression and extracellular matrix secretion of peripheral blood-derived mesenchymal stem cells (PB-MSCs). Notably, after tracing the transplanted cells by detecting the rabbit sex-determining region Y-linked gene sequence, the allogeneic PB-MSCs are found to survive for even 3 months in the regenerated cartilage. Here, the long-term release of KGN is able to efficiently and persistently activate multiple genes and signaling pathways to promote the chondrogenesis, chondrocyte differentiation, and survival of PB-MSCs. Thus, the regenerated tissues exhibit well-matched histomorphology and biomechanical performance such as native cartilage. Consequently, it is believed this innovative work can expand the choice for developing the next generation of orthopedic implants in the loadbearing region of a living body.

The position of the posterolateral bundle femoral tunnel during arthroscopic double-bundle anterior cruciate ligament reconstruction: a cadaveric study.

PURPOSE: The purpose was to find a simple guideline to help establish accurate positioning of the posterolateral bundle (PLB) femoral bone tunnel during double-bundle anterior cruciate ligament reconstruction by measuring the distance between the center of the PLB femoral footprint to the shallow and the deep articular cartilage borders of the lateral wall of the intercondylar notch. METHODS: The femoral insertions of the anteromedial bundle and PLB of the anterior cruciate ligament were dissected in 22 male cadaveric knees, aged 25 to 45 years. By use of the intercondylar notch as the landmark, the distances between the center of the PLB femoral footprint and the shallow and the deep articular cartilage borders of the lateral wall of the intercondylar notch were measured with the knees flexed at 90°. The measured data (mean ± standard deviation) were evaluated and compared. RESULTS: The center of the PLB was positioned 8.60 ± 1.52 mm and 8.65 ± 1.54 mm from the shallow and the deep cartilage borders of the lateral wall of the intercondylar notch, respectively (P = .95). The distance between the center of the PLB footprint to the low cartilage border of the lateral intercondylar wall was 5.05 ± 0.76 mm. CONCLUSIONS: The findings suggest that the position of the center of the PLB femoral footprint is at the middle of the line joining the shallow and the deep borders of the femoral cartilage. CLINICAL RELEVANCE: Surgeons can use our results as a guideline and use the PLB footprint remnant as a reference at the same time to locate the femoral PLB tunnel in a simple, easy, and repeatable way.

Principles for establishment of the stem cell bank and its applications on management of sports injuries.

BACKGROUND: The stem cells of the stem cell banks have prominent problems for insufficient sources, easy contamination, unstable biological characteristics after serial subcultivations, and high cost. METHODS: After collecting the construction processes of the existing stem cell banks and suggestions from authoritative experts in the past 10 years, 230 reference principles were obtained, and finally, the principles of "5C" for the establishment of modern standardized stem cell banks were summarized, and their related applications on the management of sports injuries were reviewed as well. RESULTS: The basic principles of "5C" for the establishment of modern standardized stem cell banks include (1) principle of informed consent, (2) confidentiality principle, (3) conformity principle, (4) contamination-free principle, and (5) commonweal principle. The applications of stem cells on repairs, reconstructions, and regenerations of sports injuries were also reviewed, especially in tissue-engineered cartilage, tissue-engineered meniscus, and tissue-engineered ligament. CONCLUSIONS: The proposal of the basic principles of "5C" is conducive to relevant stem cell researchers and clinical medical experts to build modern stem cell banks in a more standardized and efficient manner while avoiding some major mistakes or problems that may occur in the future. On this basis, stem cells from stem cell banks would be increasingly used in the management of sports injuries. More importantly, these days, getting stem cell samples are difficult in a short time, and such banks with proper legal consent may help the scientific community.

Fabrication of Injectable Chitosan-Chondroitin Sulfate Hydrogel Embedding Kartogenin-Loaded Microspheres as an Ultrasound-Triggered Drug Delivery System for Cartilage Tissue Engineering.

Ultrasound-responsive microspheres (MPs) derived from natural polysaccharides and injectable hydrogels have been widely investigated as a biocompatible, biodegradable, and controllable drug delivery system and cell scaffolds for tissue engineering. In this study, kartogenin (KGN) loaded poly (lactide-co-glycolic acid) (PLGA) MPs (MPs@KGN) were fabricated by premix membrane emulsification (PME) method which were sonicated by an ultrasound transducer. Furthermore, carboxymethyl chitosan-oxidized chondroitin sulfate (CMC-OCS) hydrogel were prepared via the Schiff' base reaction-embedded MPs to produce a CMC-OCS/MPs scaffold. In the current work, morphology, mechanical property, porosity determination, swelling property, in vitro degradation, KGN release from scaffolds, cytotoxicity, and cell bioactivity were investigated. The results showed that MPs presented an obvious collapse after ultrasound treatment. The embedded PLGA MPs could enhance the compressive elastic modulus of soft CMC-OCS hydrogel. The cumulative release KGN from MPs exhibited a slow rate which would display an appropriate collapse after ultrasound, allowing KGN to maintain a continuous concentration for at least 28 days. Moreover, the composite CMC-OCS@MPs scaffolds exhibited faster gelation, lower swelling ratio, and lower in vitro degradation. CCK-8 and LIVE/DEAD staining showed these scaffolds did not influence rabbit bone marrow mesenchymal stem cells (rBMMSCs) proliferation. Then these scaffolds were cultured with rBMMSCs for 2 weeks, and the immunofluorescent staining of collagen II (COL-2) showed that CMC-OCS hydrogel embedded with MPs@KGN (CMC-OCS@MPs@KGN) with ultrasound had the ability to increase the COL-2 synthesis. Overall, due to the improved mechanical property and the ability of sustained KGN release, this injectable hydrogel with ultrasound-responsive property is a promising system for cartilage tissue engineering.

Scaffold-Based Tissue Engineering Strategies for Osteochondral Repair.

Over centuries, several advances have been made in osteochondral (OC) tissue engineering to regenerate more biomimetic tissue. As an essential component of tissue engineering, scaffolds provide structural and functional support for cell growth and differentiation. Numerous scaffold types, such as porous, hydrogel, fibrous, microsphere, metal, composite and decellularized matrix, have been reported and evaluated for OC tissue regeneration in vitro and in vivo, with respective advantages and disadvantages. Unfortunately, due to the inherent complexity of organizational structure and the objective limitations of manufacturing technologies and biomaterials, we have not yet achieved stable and satisfactory effects of OC defects repair. In this review, we summarize the complicated gradients of natural OC tissue and then discuss various osteochondral tissue engineering strategies, focusing on scaffold design with abundant cell resources, material types, fabrication techniques and functional properties.