Femoral anterior condyle height decreases as the distal anteroposterior size increases in total knee arthroplasty: A comparative study.

PURPOSE: The anterior flange height of the current femoral component increases with an increasing distal femoral anteroposterior dimension. During total knee arthroplasty (TKA), we have observed that a large femur may have a thinner anterior condyle, whereas a small femur may have a thicker anterior condyle. The first purpose of this study was to examine whether the femoral anterior condyle height decreases as the distal femoral anteroposterior size increases and whether gender differences exist in anterior condyle height. METHODS: A total of 1218 knees undergoing TKA intraoperative and computed tomography scans from 303 healthy knees were used to measure the anterior lateral condylar height (ALCH), anterior medial condylar height (AMCH), and the lateral anteroposterior (LAP) and medial anteroposterior (MAP) dimensions of distal femurs. The LAP and MAP measurements were used for adjustments to determine whether gender differences exist in anterior condyle heights. Linear regression analysis was performed to determine correlations between ALCH and LAP or between AMCH and MAP. RESULTS: There were significant differences between males and females in ALCH in both the CT and TKA groups and AMCH in the CT group (all P<0.01). After adjusting for LAP and MAP, there were significant gender differences in the lateral and medial condylar heights in both groups (P<0.01). There were significant negative correlations between ALCH and LAP values and between AMCH and MAP values in both CT and TKA measurements, with the LAP and MAP values increasing as ALCH and AMCH decreased. CONCLUSIONS: The results demonstrate that femoral anterior condylar height decreased with increasing anteroposterior dimension in both the medial and lateral condyle. In addition, this study also showed that anterior condylar heights are highly variable, with gender differences. The data may provide an important reference for designing femoral anterior flange thickness to precisely match the natural anterior condylar anatomy.

The Relationship Between Prognostic Nutritional Indexes and the Clinical Outcomes of Patients with Acute Exacerbation of Chronic Obstructive Pulmonary Disease.

Purpose: Nutritional status is related to the clinical outcomes of patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD). The aim of this study was to investigate the association between nutritional status, measured by the prognostic nutritional index (PNI), and adverse hospitalization outcomes in patients with AECOPD. Methods: Consecutive AECOPD patients admitted to the First Affiliated Hospital of Sun Yat-sen University between January 1, 2015 to October 31, 2021 were enrolled. We collected the clinical characteristics and laboratory data of patients. Multivariable logistic regression models were developed to assess the relationship between the baseline PNI and adverse hospitalization outcomes. A generalized additive model (GAM) was used to identify any non-linear relationship. In addition, we performed a subgroup analysis to tested the robustness of the results. Results: A total of 385 AECOPD patients were involved in this retrospective cohort study. Based on the tertiles of PNI, patients in the lower tertiles of PNI showed more worse outcome incidence (30 [23.6%] versus 17 [13.2%] versus 8 [6.2%]; p < 0.001). Multivariable logistic regression analysis revealed that the PNI were independently associated with adverse hospitalization outcomes after adjustment for confounding factors (Odds ratio [OR] = 0.94, 95% CI: 0.91 to 0.97, P < 0.0001). After adjusting for confounders, smooth curve fitting showed a saturation effect, suggesting that the relationship between the PNI and adverse hospitalization outcomes was nonlinear. Two-piecewise linear regression model suggested that the incidence of adverse hospitalization outcomes significantly decreased with PNI level up to the inflection point (PNI = 42), and PNI was not associated with adverse hospitalization outcome after that point. Conclusion: Decreased PNI levels at admission were determined to be associated with adverse hospitalization outcomes in patients with AECOPD. The results obtained in this study may potentially assist clinicians optimize risk evaluations and clinical management processes.

An immunomodulatory polypeptide hydrogel for osteochondral defect repair.

Osteochondral injury is a common and frequent orthopedic disease that can lead to more serious degenerative joint disease. Tissue engineering is a promising modality for osteochondral repair, but the implanted scaffolds are often immunogenic and can induce unwanted foreign body reaction (FBR). Here, we prepare a polypept(o)ide-based PAA-RGD hydrogel using a novel thiol/thioester dual-functionalized hyperbranched polypeptide P(EG3Glu-co-Cys) and maleimide-functionalized polysarcosine under biologically benign conditions. The PAA-RGD hydrogel shows suitable biodegradability, excellent biocompatibility, and low immunogenicity, which together lead to optimal performance for osteochondral repair in New Zealand white rabbits even at the early stage of implantation. Further in vitro and in vivo mechanistic studies corroborate the immunomodulatory role of the PAA-RGD hydrogel, which induces minimum FBR responses and a high level of polarization of macrophages into the immunosuppressive M2 subtypes. These findings demonstrate the promising potential of the PAA-RGD hydrogel for osteochondral regeneration and highlight the importance of immunomodulation. The results may inspire the development of PAA-based materials for not only osteochondral defect repair but also various other tissue engineering and bio-implantation applications.

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.

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.

Association of Red Cell Index and Adverse Hospitalization Outcomes in Chronic Obstructive Pulmonary Disease Patients with Acute Exacerbation: A Retrospective Cohort Study.

Purpose: Previous studies have shown that the red cell index (RCI) can be considered as a simple and useful method to evaluate respiratory function. However, at present its association with adverse hospitalization outcomes in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD) is not fully understood. Our study aimed to examine the relationship between adverse hospitalization outcomes and RCI among AECOPD patients. Patients and Methods: We performed a retrospective analysis of consecutive patients from January 2015 to October 2021. In this study, RCI was the independent variable, measured at baseline, and adverse hospitalization outcome was the dependent variable. According to the RCI median (RCI=2.221), we divided 377 patients into two roughly equal groups (188 and 189, respectively). Next, the association between RCI and adverse hospitalization outcomes was explored using multivariable logistic regression models. To identify any non-linear relationship, a generalized additive model (GAM) was employed. Results: With a total of 377 patients with AECOPD, we divided them into two roughly equal groups to compare the clinical factors and RCI levels. The patients in the higher RCI group showed poorer outcome incidence (18 [9.57%] vs 31 [16.40%]; p = 0.049). After accounting for potential confounders, the results showed that RCI was positively associated with adverse hospitalization outcomes (odds ratio [OR] = 1.15, 95% CI: 1.01-1.32). In addition, a non-linear relationship was detected between RCI and adverse hospitalization outcomes, which had an inflection point of 3.2. There were odds ratios and confidence intervals of 0.8 (0.7-1.0) and 1.3 (1.2-1.4) on the left and right sides of the inflection point, respectively. Conclusion: The RCI and adverse hospitalization outcomes exhibited a non-linear relationship in the AECOPD patients. RCI is strongly positively correlated with adverse hospitalization outcomes when it was greater than 3.2.

Physical therapy and orthopaedic equipment-induced reduction in the biomechanical risk factors related to knee osteoarthritis: a systematic review and Bayesian network meta-analysis of randomised controlled trials.

OBJECTIVE: Are physical therapy or orthopaedic equipment efficacious in reducing the biomechanical risk factors in people with tibiofemoral osteoarthritis (OA)? Is there a better therapeutic intervention than others to improve these outcomes? DESIGN: Systematic review with network meta-analysis (NMA) of randomised trials. DATA SOURCES: PubMed, Web of Science, Cochrane Library, Embase and MEDLINE were searched through January 2021. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: We included randomised controlled trials exploring the benefits of using physical therapy or orthopaedic equipment in reducing the biomechanical risk factors which included knee adduction moment (KAM) and knee adduction angular impulse (KAAI) in individuals with tibiofemoral OA. DATA EXTRACTION AND SYNTHESIS: Two authors extracted data independently and assessed risk of bias. We conducted an NMA to compare multiple interventions, including both direct and indirect evidences. Heterogeneity was assessed (sensitivity analysis) and quantified (I2 statistic). Grading of Recommendations Assessment, Development and Evaluation assessed the certainty of the evidence. RESULTS: Eighteen randomised controlled trials, including 944 participants, met the inclusion criteria, of which 14 trials could be included in the NMA. Based on the collective probability of being the overall best therapy for reducing the first peak KAM, lateral wedge insoles (LWI) plus knee brace was closely followed by gait retraining, and knee brace only. Although no significant difference was observed among the eight interventions, variable-stiffness shoes and neuromuscular exercise exhibited an increase in the first peak KAM compared with the control condition group. And based on the collective probability of being the overall best therapy for reducing KAAI, gait retraining was followed by LWI only, and lower limb exercise. CONCLUSION: The results of our study support the use of LWI plus knee brace for reducing the first peak KAM. Gait retraining did not rank highest but it influenced both KAM and KAAI and therefore it was the most recommended therapy for reducing the biomechanical risk factors.

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.

Fabrication of 3D-Printed Interpenetrating Hydrogel Scaffolds for Promoting Chondrogenic Differentiation.

The limited self-healing ability of cartilage necessitates the application of alternative tissue engineering strategies for repairing the damaged tissue and restoring its normal function. Compared to conventional tissue engineering strategies, three-dimensional (3D) printing offers a greater potential for developing tissue-engineered scaffolds. Herein, we prepared a novel photocrosslinked printable cartilage ink comprising of polyethylene glycol diacrylate (PEGDA), gelatin methacryloyl (GelMA), and chondroitin sulfate methacrylate (CSMA). The PEGDA-GelMA-CSMA scaffolds possessed favorable compressive elastic modulus and degradation rate. In vitro experiments showed good adhesion, proliferation, and F-actin and chondrogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) on the scaffolds. When the CSMA concentration was increased, the compressive elastic modulus, GAG production, and expression of F-actin and cartilage-specific genes (COL2, ACAN, SOX9, PRG4) were significantly improved while the osteogenic marker genes of COL1 and ALP were decreased. The findings of the study indicate that the 3D-printed PEGDA-GelMA-CSMA scaffolds possessed not only adequate mechanical strength but also maintained a suitable 3D microenvironment for differentiation, proliferation, and extracellular matrix production of BMSCs, which suggested this customizable 3D-printed PEGDA-GelMA-CSMA scaffold may have great potential for cartilage repair and regeneration in vivo.

MicroRNA-210-3p Promotes Chondrogenic Differentiation and Inhibits Adipogenic Differentiation Correlated with HIF-3α Signalling in Bone Marrow Mesenchymal Stem Cells.

Cartilage injury of the knee joint is very common. Due to the limited self-healing ability of articular cartilage, osteoarthritis is very likely to occur if left untreated. Bone marrow mesenchymal stem cells (BMMSCs) are widely used in the study of cartilage injury due to their low immunity and good amplification ability, but they still have disadvantages, such as heterogeneous undifferentiated cells. MicroRNAs can regulate the chondrogenic differentiation ability of MSCs by inhibiting or promoting mRNA translation and degradation. In this research, we primarily investigated the effect of microRNA-210-3p (miR-210-3p) on chondrogenic and adipogenic differentiation of BMMSCs in vitro. Our results demonstrate that miR-210-3p promoted chondrogenic differentiation and inhibited adipogenic differentiation of rat BMMSCs, which was related to the HIF-3α signalling pathway. Additionally, miR-210-3p promotes mRNA and protein levels of the chondrogenic expression genes COLII and SOX9 and inhibits mRNA and protein levels of the adipogenic expression genes PPARγ and LPL. Thus, miR-210-3p combined with BMMSCs is a candidate for future clinical applications in cartilage regeneration and could represent a promising new therapeutic target for OA.

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.

Function and Mechanism of RGD in Bone and Cartilage Tissue Engineering.

Bone and cartilage injury is common, tissue engineered scaffolds are potential means to repair. Because most of the scaffold materials used in bone and cartilage tissue engineering are bio-inert, it is necessary to increase the cellular adhesion ability of during tissue engineering reconstruction. The Arginine - Glycine - Aspartic acid (Arg-Gly-Asp, RGD) peptide family is considered as a specific recognition site for the integrin receptors. Integrin receptors are key regulators of cell-cell and cell-extracellular microenvironment communication. Therefore, the RGD polypeptide families are considered as suitable candidates for treatment of a variety of diseases and for the regeneration of various tissues and organs. Many scaffold material for tissue engineering and has been approved by US Food and Drug Administration (FDA) for human using. The application of RGD peptides in bone and cartilage tissue engineering was reported seldom. Only a few reviews have summarized the applications of RGD peptide with alloy, bone cements, and PCL in bone tissue engineering. Herein, we summarize the application progress of RGD in bone and cartilage tissue engineering, discuss the effects of structure, sequence, concentration, mechanical stimulation, physicochemical stimulation, and time stimulation of RGD peptide on cells differentiation, and introduce the mechanism of RGD peptide through integrin in the field of bone and cartilage tissue engineering.

Tibial Tubercle Osteotomy May Not Provide Additional Benefit in Treating Patellar Dislocation With Increased Tibial Tuberosity-Trochlear Groove Distance: A Systematic Review.

PURPOSE: To examine the indications and outcomes of medial patellofemoral ligament reconstruction (MPFLR) with or without tibial tubercle osteotomy (TTO) in treating recurrent or habitual patellar dislocation with an increased tibial tuberosity-trochlear groove (TT-TG) distance. METHODS: We performed a literature search of the established medical databases Cochrane Central, PubMed-MEDLINE, EMBASE, and Web of Science. The inclusion criteria were as follows: skeletally mature patients with recurrent or habitual patellar dislocation and an increased TT-TG distance, treatment with MPFLR combined with a TTO procedure or isolated MPFLR, and reporting of clinical outcomes and complications. Each study was assessed for quality and the level of evidence. The general characteristics, indications, surgical techniques, TT-TG distance, clinical results, imaging evaluation findings, and complications of each study were recorded. RESULTS: Nine studies consisting of 288 knees met the inclusion criteria. The average Coleman score was 71.56 (range, 55-83). The threshold for an increased TT-TG distance ranged from 16 to 20 mm in the included studies. Similar good postoperative outcomes were reported in patients with an increased TT-TG distance treated with MPFLR with versus without a TTO procedure. The mean postoperative Lysholm score ranged from 75.0 to 94.7 (I2 = 87.6%) in the isolated MPFLR group and from 85.0 to 87.6 (I2 = 16.3%) in the TTO-with-MPFLR group. Similar postoperative congruence angles were reported in both groups. The postoperative redislocation rate ranged from 0% to 4.2% in the TTO-with-MPFLR group, and no redislocation was found in the isolated MPFLR group. The postoperative apprehension sign was only reported in isolated MPFLR patients. CONCLUSIONS: The outcomes of MPFLR with or without TTO to treat recurrent or habitual patellar dislocation with an increased TT-TG distance appeared similar. However, this study was limited by the considerable heterogeneity, variety of techniques, variety of TT-TG distances, and variability in patella alta and trochlear dysplasia among the included studies. LEVEL OF EVIDENCE: Level IV, systematic review of Level II to IV studies.

The Higher Inherent Therapeutic Potential of Biomaterial-Based hDPSCs and hEnSCs for Pancreas Diseases.

Human endometrial stem cells (hEnSCs), dental pulp stem cells (hDPSCs) and adipose tissue-derived stem cells (hADSCs) are considered to be the promising candidates for the treatment of pancreas diseases. The prognosis is better with in situ injection of mesenchymal stem cells (MSCs) to the damaged pancreas compared with intravenous injection. However, the clinical application of these cells are limited, due to poor engraftment of transplanted cells after delivery. On the other hand, understanding the role of the biomaterials in cell therapy is essential to promote the therapeutic effects of MSCs. Matrigel, a basement membrane matrix biomaterial, is rich in laminin and collagen IV. The aim of this study is to investigate the difference of biological characteristics of hEnSCs, hDPSCs and hADSCs in vitro and their survival situation with Matrigel post intrapancreatic transplantation in vivo. Our findings showed, firstly, there was no significant difference in morphology and immunophenotype of these MSCs. Secondly, the biological properties, including cell proliferation, the ability of adipogenic and osteogenic differentiation and the mRNA expression levels of pancreas development-related genes, have been showed distinct difference among these MSCs. Thirdly, Matrigel can improve the survival of MSCs in vivo, especially for Matrigel-based hDPSCs and Matrigel-based hEnSCs in pancreas parenchyma of SD rats. These results suggest that hDPSCs and hEnSCs are with the greater inherent therapeutic potential for pancreas diseases compared with hADSCs.

Loop changes after knee flexion-extension movement in a cadaveric anterior cruciate reconstruction model.

BACKGROUND: Recently, adjustable-loop devices (ALDs) have been widely used, and their reliability has always been the focus of attention. This study compared loop length changes under pull stress caused by flexion and extension of the cadaver knee between ALDs and fixed-loop devices (FLDs) in terms of femoral fixation after anterior cruciate ligament (ACL) reconstruction. METHODS: ACL reconstruction in cadaveric knee joints was performed under arthroscopy with femoral suspension devices and tibial fixation by tying sutures on staples. The knee joint was repeatedly flexed and extended 30 times after fixation. According to the femoral fixation device used (Endobutton or Ultrabutton), the knee joints were divided into two groups: the ALD group (12 specimens) and the FLD group (ten specimens). The length of the loop before and after fixation was measured, and the loop length of the ALD group was re-measured 1 day after reconstruction. RESULTS: There was no significant difference in the length of the loop between the two groups (t = 0.579, P = 0.569). One day later, the loop length of the ALDs retracted by 0.29 ±â€Š0.33 (0-1.1) mm, and there was no retraction in three specimens. CONCLUSION: There was no significant difference in the loop length under flexion and extension stress after ACL reconstruction between ALDs and FLDs.

Facile Strategy on Hydrophilic Modification of Poly(ε-caprolactone) Scaffolds for Assisting Tissue-Engineered Meniscus Constructs In Vitro.

Poly(ε-caprolactone) (PCL) derived scaffolds have been extensively explored in the field of tissue-engineered meniscus (TEM) originating from their good biosafety and biomechanical properties. However, the poor intrinsic hydrophobicity severely hindered their wide applications for the scaffold-assisted tissue regeneration. Herein, we developed a simple strategy on surface modification of three-dimensional (3D) PCL scaffolds via a simply soaking treatment of sodium hydroxide (NaOH) solutions to increase the hydrophilicity and roughness of scaffolds' surfaces. We investigated the effect of hydrolysis degree mediated by NaOH solutions on mechanical properties of 3D scaffolds, considering the importance of scaffolds' resistance to internal force. We also investigated and analyzed the biological performances of mesenchymal stromal cells (MSCs) and meniscal fibrocartilage cells (MFCs) onto the scaffolds treated or untreated by NaOH solutions. The results indicated that hydrophilic modification could improve the proliferation and attachment of cells on the scaffolds. After careful screening process condition, structural fabrication, and performance optimization, these modified PCL scaffolds possessed roughened surfaces with inherent hierarchical pores, enhanced hydrophilicity and preferable biological performances, thus exhibiting the favorable advantages on the proliferation and adhesion of seeded cells for TEM. Therefore, this feasible hydrophilic modification method is not only beneficial to promote smarter biomedical scaffold materials but also show great application prospect in tissue engineering meniscus with tunable architectures and desired functionalities.

The Use of Peripheral Blood-Derived Stem Cells for Cartilage Repair and Regeneration In Vivo: A Review.

BACKGROUND: Peripheral blood (PB) is a potential source of chondrogenic progenitor cells that can be used for cartilage repair and regeneration. However, the cell types, isolation and implantation methods, seeding dosage, ultimate therapeutic effect, and in vivo safety remain unclear. METHODS: PubMed, Embase, and the Web of Science databases were systematically searched for relevant reports published from January 1990 to December 2019. Original articles that used PB as a source of stem cells to repair cartilage in vivo were selected for analysis. RESULTS: A total of 18 studies were included. Eight human studies used autologous nonculture-expanded PB-derived stem cells (PBSCs) as seed cells with the blood cell separation isolation method, and 10 animal studies used autologous, allogenic or xenogeneic culture-expanded PB-derived mesenchymal stem cells (PB-MSCs), or nonculture-expanded PBSCs as seed cells. Four human and three animal studies surgically implanted cells, while the remaining studies implanted cells by single or repeated intra-articular injections. 121 of 130 patients (in 8 human clinical studies), and 230 of 278 animals (in 6 veterinary clinical studies) using PBSCs for cartilage repair achieved significant clinical improvement. All reviewed articles indicated that using PB as a source of seed cells enhances cartilage repair in vivo without serious adverse events. CONCLUSION: Autologous nonculture-expanded PBSCs are currently the most commonly used cells among all stem cell types derived from PB. Allogeneic, autologous, and xenogeneic PB-MSCs are more widely used in animal studies and are potential seed cell types for future applications. Improving the mobilization and purification technology, and shortening the culture cycle of culture-expanded PB-MSCs will obviously promote the researchers' interest. The use of PBSCs for cartilage repair and regeneration in vivo are safe. PBSCs considerably warrant further investigations due to their superiority and safety in clinical settings and positive effects despite limited evidence in humans.

Advances of Stem Cell-Laden Hydrogels With Biomimetic Microenvironment for Osteochondral Repair.

Osteochondral damage from trauma or osteoarthritis is a general joint disease that can lead to an increased social and economic burden in the modern society. The inefficiency of osteochondral defects is mainly due to the absence of suitable tissue-engineered substrates promoting tissue regeneration and replacing damaged areas. The hydrogels are becoming a promising kind of biomaterials for tissue regeneration. The biomimetic hydrogel microenvironment can be tightly controlled by modulating a number of biophysical and biochemical properties, including matrix mechanics, degradation, microstructure, cell adhesion, and intercellular interactions. In particular, advances in stem cell-laden hydrogels have offered new ideas for the cell therapy and osteochondral repair. Herein, the aim of this review is to underpin the importance of stem cell-laden hydrogels on promoting the development of osteochondral regeneration, especially in the field of manipulation of biomimetic microenvironment and utilization growth factors with various delivery methods.

Low-Molecular-Weight Heparin-Functionalized Chitosan-Chondroitin Sulfate Hydrogels for Controlled Release of TGF-ß3 and in vitro Neocartilage Formation.

Repair of hyaline cartilage remains a huge challenge in clinic because of the avascular and aneural characteristics and the paucity of endogenous repair cells. Recently, tissue engineering technique, possessing unique capacity of repairing large tissue defects, avoiding donor complications and two-stage invasive surgical procedures, has been developed a promising therapeutic strategy for cartilage injury. In this study, we incorporated low-molecular-weight heparin (LMWH) into carboxymethyl chitosan-oxidized chondroitin sulfate (CMC-OCS) hydrogel for loading transforming growth factor-ß3 (TGF-ß3) as matrix of peripheral blood mesenchymal stem cells (PB-MSCs) to construct tissue-engineered cartilage. Meanwhile, three control hydrogels with or without LMWH and/or TGF-ß3 were also prepared. The gelling time, microstructures, mechanical properties, degradation rate, cytotoxicity, and the release of TGF-ß3 of different hydrogels were investigated. In vitro experiments evaluated the tri-lineage differentiation potential of PB-MSCs, combined with the proliferation, distribution, viability, morphology, and chondrogenic differentiation. Compared with non-LMWH-hydrogels, LMWH-hydrogels (LMWH-CMC-OCS-TGF-ß3) have shorter gelling time, higher mechanical strength, slower degradation rate and more stable and lasting release of TGF-ß3. After two weeks of culture in vitro, expression of cartilage-specific genes collagen type-2 (COL-2) and aggrecan (AGC), and secretion of glycosaminoglycan (GAG), and COL-2 proteins in LMWH-CMC-OCS-TGF-ß3 group were significantly higher than those in other groups. COL-2 immunofluorescence staining showed that the proportion of COL-2 positive cells and immunofluorescence intensity in LMWH-CMC-OCS-TGF-ß3 hydrogel were significantly higher than those in other groups. The LMWH-CMC-OCS-TGF-ß3 hydrogel can slowly release TGF-ß3 in a long term, and meanwhile the hydrogel can provide a biocompatible microenvironment for the growth and chondrogenic differentiation of PB-MSCs. Thus, LMWH functionalized CMC-OCS hydrogels proposed in this work will be beneficial for constructing functional scaffolds for tissue-engineered cartilage.

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.