Articular Cartilage Defects Of Knee Research Articles

Exosomes derived from platelet-rich plasma present a novel potential in repairing knee articular cartilage defect combined with cyclic peptide-modified β-TCP scaffold

BackgroundThe aim of this study was to investigate the therapeutic effects and mechanisms of PRP-exos combined with cyclic peptide-modified β-TCP scaffold in the treatment of rabbit knee cartilage defect.MethodsPRP-exos were extracted and characterized by TEM, NTA and WB. The therapeutic effects were evaluated by ICRS score, HE staining, Immunohistochemistry, qRT-PCR and ELISA. The repair mechanism of PRP-exos was estimated and predicted by miRNA sequencing analysis and protein–protein interaction network analysis.ResultsThe results showed that PRP-exos had a reasonable size distribution and exhibited typical exosome morphology. The combination of PRP-exos and cyclic peptide-modified β-TCP scaffold improved ICRS score and the expression level of COL-2, RUNX2, and SOX9. Moreover, this combination therapy reduced the level of MMP-3, TNF-α, IL-1β, and IL-6, while increasing the level of TIMP-1. In PRP-exos miRNA sequencing analysis, the total number of known miRNAs aligned across all samples was 252, and a total of 91 differentially expressed miRNAs were detected. The results of KEGG enrichment analysis and the protein–protein interaction network analysis indicated that the PI3K/AKT signaling pathway could impact the function of chondrocytes by regulating key transcription factors to repair cartilage defect.ConclusionPRP-exos combined with cyclic peptide-modified β-TCP scaffold effectively promoted cartilage repair and improved chondrocyte function in rabbit knee cartilage defect. Based on the analysis and prediction of PRP-exos miRNAs sequencing, PI3K/AKT signaling pathway may contribute to the therapeutic effect. These findings provide experimental evidence for the application of PRP-exos in the treatment of cartilage defect.

A Novel Scaffold of Icariin/Porous Magnesium Alloy-Repaired Knee Cartilage Defect in Rat by Wnt/β-Catenin Signaling Pathway.

Cartilage defects caused by joint diseases are difficult to treat clinically. Tissue engineering materials provide a new means to promote the repair of cartilage defects. The purpose of this study is to design a novel scaffold of porous magnesium alloy loaded with icariin and sustained release in order to explore the effect and possible mechanism of this scaffold in repairing SD rat knee articular cartilage defect. We constructed a novel type of icariin/porous magnesium alloy scaffold, observed the structure of the scaffold by electron microscope, detected the drug release of icariin in the scaffold and the biological safety, and established an animal model of cartilage defect in the femoral intercondylar fossa of the knee joint in rats; the scaffold was placed in the defect. After 12 weeks of repair, the rat knee articular cartilage repair was evaluated by gross specimens and micro-CT, HE, safranin O-fast green, and toluidine blue staining combined with the modified Mankin's score. The protein expressions of the Wnt/β-catenin signaling pathway-related factors (β-catenin, Wnt5a, Wnt1, sFRP1) and chondrogenic differentiation-related factors (Sox9, Aggrecan, Col2α1) were detected by immunohistochemical staining. We found that the novel scaffold of icariin/porous magnesium alloy can release icariin slowly and has biosafety in rats. Compared with other groups, icariin/porous magnesium alloy can significantly promote the repair of cartilage defects and the expressions of β-catenin, Wnt5a, Wnt1, Sox9, Aggrecan, and Col2α1 (P < 0.05). This novel scaffold can promote the repair of rat knee cartilage defects, and this process may be achieved by activating the Wnt/β-catenin signaling pathway.

Comparison of Knee Articular Cartilage Defect Size Between Measurements Obtained on Preoperative MRI Versus During Arthrotomy.

Treatment decisions for cartilage defects are often based on lesion size. Magnetic resonance imaging (MRI) is widely used to diagnose cartilage defects noninvasively; however, their size estimated from MRI may differ from defect sizes measured during arthrotomy, especially after debridement to healthy cartilage if undergoing autologous chondrocyte implantation. The purpose of this study was to evaluate the reliability of 2 methods to assess knee cartilage defect size on preoperative MRI and determine their accuracy in predicting postdebridement defect sizes recorded during arthrotomy. It was hypothesized that defect size would be predicted more accurately by the total area of abnormal articular cartilage rather than the area of full-thickness cartilage loss as identified on MRI. Cohort study (diagnosis); Level of evidence, 3. This study included 64 patients (mean age, 41.8 ± 9.6 years) who underwent autologous cell therapy. Each patient received a 3-T MRI at 6.1 ± 3.0 weeks before cell implantation. Three raters, a radiologist, a surgeon, and a scientist, measured (1) the full-thickness cartilage defect area and (2) the total predicted abnormal cartilage area, identified by an abnormal signal on MRI. Interrater reliability was assessed using the intraclass correlation coefficient (ICC). Actual pre- and postdebridement defect sizes were obtained from intraoperative surgical notes. Postdebridement surgical measurements were considered the clinical reference standard and were compared with the radiologist's MRI measurements. Eighty-seven defects were assessed, located on the lateral (n = 8) and medial (n = 26) femoral condyle, trochlea (n = 17), and patella (n = 36). The interrater reliability of the cartilage defect measurements on MRI was good to excellent for the full-thickness cartilage defect area (ICC = 0.74) and the total predicted abnormal cartilage area (ICC = 0.78). The median full-thickness cartilage defect area on MRI underestimated the median postdebridement defect area by 78.3%, whereas the total predicted abnormal cartilage area measurement underestimated the postdebridement defect area by 14.3%. Measuring the full-thickness cartilage defect area on MRI underestimated the area to treat, whereas measuring the total abnormal area provided a better estimate of the actual defect size for treatment.

Poster 365: Initial outcomes after unicompartmental tibiofemoral bipolar osteochondral and meniscus allograft transplantation in the knee using high-viability tissues

Objectives: To report initial outcomes for unicompartmental tibiofemoral bipolar osteochondral allograft transplantation (OCAT) with meniscus allograft transplantation (MAT) using fresh high-cell- viability tissues for treatment of knee articular cartilage defects with meniscus deficiency. The study was designed to test the hypothesis that primary OCAT and MAT using high-viability tissues will be associated with successful short-term (2 to 6 years) outcomes based on statistically significant and clinically meaningful improvements in pain and function in the majority of patients. Methods: With IRB approval and documented informed consent, patients who underwent primary OCAT and MAT for large articular cartilage defects with meniscus deficiency involving at least one femoral condyle, tibial plateau, and meniscus, all of which were opposing (bipolar). Surgeries were defined as Uni when patients underwent OCAT and MAT involving one femoral condyle, tibial plateau, and meniscus in the same compartment or Uni-Plus when patients underwent Uni OCAT and MAT with at least one other OCA transplant to treat a large (&gt;2.5cm2) grade III or IV focal articular cartilage defect of the patella, trochlea, femoral condyle, or tibial plateau. Patients who had at least 2-year follow up data regarding complications, failures, adherence, and patient reported outcome measures (PROMs) were analyzed. Patients who required OCA and/or MAT revision or artificial arthroplasty were defined as treatment failures. Patient reported outcome measures (PROMs) including VAS pain, IKDC, SANE, PROMIS Global Health and Physical Function, were collected at 3 and 6 months and then yearly after transplantation. Outcomes were compared based on patient sex, age, and BMI, tobacco use, previous and concurrent procedures, differences in number of surfaces transplanted (Uni vs Uni-Plus), and adherence. Significance was set at P &lt; 0.05. Differences in PROMs were also assessed for minimum clinically important differences. Results: Seventy-six patients (n=52 males; 68%) met inclusion criteria (mean followup = 52 months; median = 56 months; range, 24-70 months). Mean age was 41.1 years (range, 15-69 years) and mean body mass index (BMI) was 28.9 kg/m2 (range, 17-46). Forty-eight patients underwent OCAT(s) in addition to Uni (Uni-Plus). Eight patients (10.5%) underwent concurrent ACL reconstruction, and 28 patients (36.8%) underwent ipsilateral lower extremity osteotomy in order to address co-morbidities. Twenty-three patients (30.3%) were documented to be non-adherent during the first year after transplantation. Initial (&gt;2-year) success rate was 77.6% with 8 patients (10.5%) undergoing OCA and/or MAT revision and 9 patients (11.8%) converted to arthroplasty. Variables associated with increased risk for treatment failure (revision or arthroplasty) included ipsilateral osteotomy (p = .046; OR = 3.3), ipsilateral concurrent procedure (p = .0057; OR = 5.5), and non-adherence (p = .0009; OR = 7.2). None of the patients undergoing OCA and/or MAT revision surgery in the present study required arthroplasty at the time of data analysis such that overall success rate for primary and revision unicompartmental bipolar OCA plus MAT was 88.2%. There were statistically significant (p &lt; .0001) and clinically important improvements from preoperative levels for all patient reported outcomes at each annual follow-up time point. Conclusions: Unicompartmental tibiofemoral bipolar osteochondral and meniscus allograft transplantation can result in successful short-term (2 to 6 years) outcomes and satisfaction in the majority (78%) of patients. Primary MOPS-preserved OCAT and MAT for treatment of femoral condyle and tibial plateau articular cartilage defects with concurrent meniscus deficiency was associated with statistically significant and clinically meaningful improvements in patient-reported measures of pain and function.

Glycopolypeptide hydrogels with adjustable enzyme-triggered degradation: A novel proteoglycans analogue to repair articular-cartilage defects.

Proteoglycans (PGs), also known as a viscous lubricant, is the main component of the cartilage extracellular matrix (ECM). The loss of PGs is accompanied by the chronic degeneration of cartilage tissue, which is an irreversible degeneration process that eventually develops into osteoarthritis (OA). Unfortunately, there is still no substitute for PGs in clinical treatments. Herein, we propose a new PGs analogue. The Glycopolypeptide hydrogels in the experimental groups with different concentrations were prepared by Schiff base reaction (Gel-1, Gel-2, Gel-3, Gel-4, Gel-5 and Gel-6). They have good biocompatibility and adjustable enzyme-triggered degradability. The hydrogels have a loose and porous structure suitable for the proliferation, adhesion, and migration of chondrocytes, good anti-swelling, and reduce the reactive oxygen species (ROS) in chondrocytes. In vitro experiments confirmed that the glycopolypeptide hydrogels significantly promoted ECM deposition and up-regulated the expression of cartilage-specific genes, such as type-II collagen, aggrecan, and glycosaminoglycans (sGAG). In vivo, the New Zealand rabbit knee articular cartilage defect model was established and the hydrogels were implanted to repair it, the results showed good cartilage regeneration potential. It is worth noting that the Gel-3 group, with a pore size of 122​±​12​μm, was particularly prominent in the above experiments, and provides a theoretical reference for the design of cartilage-tissue regeneration materials in the future.

Initial Outcomes After Unicompartmental Tibiofemoral Bipolar Osteochondral and Meniscal Allograft Transplantation in the Knee Using MOPS-Preserved Fresh (Viable) Tissues

Background: Unicompartmental tibiofemoral bipolar osteochondral allograft transplantation (OCAT) with meniscal allograft transplantation (MAT) has not historically been associated with consistently successful outcomes for treatment of knee articular cartilage defects with meniscal deficiency. Hypothesis: Primary OCAT and MAT using fresh tissues will be associated with successful short-term outcomes based on statistically significant and clinically meaningful improvements in pain and function in the majority of patients. Study Design: Case series; Level of evidence, 4. Methods: Patients were prospectively enrolled into a registry for outcomes after OCAT and MAT. Patients included those who underwent primary OCAT and MAT using Missouri Osteochondral Preservation System (MOPS)–preserved allografts for treatment of large bipolar tibiofemoral articular cartilage defects with meniscal deficiency and had a minimum of 2-year follow-up data. Results: A total of 76 patients (n = 52 male; 68%) met inclusion criteria (mean follow-up, 52 months). The mean age was 41.1 years (range, 15-69 years), and the mean body mass index was 28.9 (range, 17-46); 48 patients underwent another OCAT in addition to the unicompartmental bipolar tibiofemoral OCAT and MAT; 23 patients (30.3%) were documented to be nonadherent to the prescribed postoperative restriction and rehabilitation protocol. The initial success rate (>2 years) was 77.6%, with 8 patients (10.5%) undergoing revision and 9 (11.8%) converting to arthroplasty. Variables associated with an increased risk for treatment failure (revision or arthroplasty) included ipsilateral osteotomy (P = .046; odds ratio [OR] = 3.3), ipsilateral concurrent procedure (P = .0057; OR = 5.5), and nonadherence (P = .0009; OR = 7.2). None of the patients undergoing revision surgery required arthroplasty at the time of data analysis such that the overall success rate for primary and revision unicompartmental bipolar OCA plus MAT was 88.2%. There were statistically significant (P < .0001) and clinically important improvements for all patient-reported outcomes at each annual follow-up time point. Conclusion: Unicompartmental tibiofemoral bipolar OCAT and MAT can result in successful short-term outcomes (2-6 years) and satisfaction in the majority of patients (78%). Primary MOPS-preserved OCAT with MAT for treatment of femoral condyle and tibial plateau articular cartilage defects with concurrent meniscal deficiency was associated with statistically significant and clinically meaningful improvements in patient-reported measures of pain and function.

Cartilage Regeneration Using Human Umbilical Cord Blood Derived Mesenchymal Stem Cells: A Systematic Review and Meta-Analysis.

Background and Objectives: Human umbilical-cord-blood-derived mesenchymal stem cells (hUCB-MSCs) have recently been used in clinical cartilage regeneration procedures with the expectation of improved regeneration capacity. However, the number of studies using hUCB-MSCs is still insufficient, and long-term follow-up results after use are insufficient, indicating the need for additional data and research. We have attempted to prove the efficacy and safety of hUCB-MSC treatment in a comprehensive analysis by including all subjects with knee articular cartilage defect or osteoarthritis who have undergone cartilage repair surgery using hUCB-MSCs. We conducted a meta-analysis and demonstrated efficacy and safety based on a systematic review. Materials and Methods: This systematic review was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. For this study, we searched the PubMed, Embase, Web of Science, Scopus, and Cochrane Library literature databases up to June 2022. A total of seven studies were included, and quality assessment was performed for each included study using the Newcastle-Ottawa Quality Assessment Scale. Statistical analysis was performed on the extracted pooled clinical outcome data, and subgroup analyses were completed. Results: A total of 570 patients were included in the analysis. In pooled analysis, the final follow-up International Knee Documentation Committee (IKDC) score showed a significant increase (mean difference (MD), -32.82; 95% confidence interval (CI), -38.32 to -27.32; p &lt; 0.00001) with significant heterogeneity (I2 = 93%, p &lt; 0.00001) compared to the preoperative score. The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores at final follow-up were significantly decreased (MD, 30.73; 95% CI, 24.10-37.36; p &lt; 0.00001) compared to the preoperative scores, with significant heterogeneity (I2 = 95%, p &lt; 0.00001). The visual analog scale (VAS) score at final follow-up was significantly decreased (MD, 4.81; 95% CI, 3.17-6.46; p &lt; 0.00001) compared to the preoperative score, with significant heterogeneity (I2 = 98%, p &lt; 0.00001). Two studies evaluated the modified Magnetic Resonance Observation of Cartilage Repair Tissue (M-MOCART) score and confirmed sufficient improvement. In a study analyzing a group treated with bone marrow aspiration concentrate (BMAC), there was no significant difference in clinical outcome or M-MOCART score, and the post-treatment International Cartilage Repair Society (ICRS) grade increased. Conclusion: This analysis demonstrated the safety, efficacy, and quality of repaired cartilage following hUCB-MSC therapy. However, there was no clear difference in the comparison with BMAC. In the future, comparative studies with other stem cell therapies or cartilage repair procedures should be published to support the superior effect of hUCB-MSC therapy to improve treatment of cartilage defect or osteoarthritis.

Osteochondral Allografts in Knee Surgery: Narrative Review of Evidence to Date.

Knee articular cartilage defects can result in significant pain and loss of function in active patients. Osteochondral allograft (OCA) transplantation offers a single-stage solution to address large chondral and osteochondral defects by resurfacing focal cartilage defects with mature hyaline cartilage. To date, OCA transplantation of the knee has demonstrated excellent clinical outcomes and long-term survivorship. However, significant variability still exists among clinicians with regard to parameters for graft acceptance, surgical technique, and rehabilitation. Technologies to optimize graft viability during storage, improve osseous integration of the allograft, and shorten recovery timelines after surgery continue to evolve. The purpose of this review is to examine the latest evidence on treatment indications, graft storage and surgical technique, patient outcomes and survivorship, and rehabilitation after surgery.

Platelet-Rich Plasma and Adipose-Derived Mesenchymal Stem Cells in Association with Arthroscopic Microfracture of Knee Articular Cartilage Defects: A Pilot Randomized Controlled Trial.

Background This study aims to compare the effects of platelet-rich plasma (PRP) alone or in combination with adipose-derived mesenchymal stem cells (AD-MSCs) in patients affected by cartilage defects, undergoing knee arthroscopic microfracture. Methods Thirty-eight patients diagnosed with a knee monocompartmental cartilage defect (Outerbridge grade IV) on the MRI, underwent an arthroscopic procedure. After the confirmation of the lesion, they all received the same bone marrow stimulation technique (microfracture) and were randomized into two groups: the first one had additional PRP injection (group A), while the second received PRP and AD-MSC injection (group B). Knee assessment and pain score were documented with Knee Injury Osteoarthritis Outcome Score (KOOS), International Knee Documentation Committee (IKDC) score, Short-Form (SF) 12, and Visual Analogue Scale (VAS) before the treatment and at 1, 3, 6, and 12 months of follow-up postoperatively. An additional arthroscopic procedure, performed in four patients for a subsequent meniscal lesion, let us evaluate cartilage evolution by performing a macro/microscopical assessment on cartilage biopsy specimens. Results At the 12-month follow-up, both groups showed a comparable functional improvement. The scores on the IKDC form, KOOS, pain VAS, and SF-12 significantly improved from baseline (p < 0.05) to 12 months postoperatively in both treatment groups. The four second-look arthroscopies showed a complete repair of the articular defects by smooth solid cartilage layer, with a good chondrocytic population, in both groups. A thick smooth hyaline-like cartilage with a predominantly viable cell population and normal mineralization (a form closely resembling native tissue) was observed in group B. Conclusions Modern regenerative medicine techniques, such as PRP and AD-MSC, associated with traditional arthroscopic bone marrow stimulating techniques, seem to enhance cartilage restoration ability. The preliminary results of this pilot study encourage the synergic use of these regenerative modulating systems to improve the quality of the regenerated cartilage.

Effect of silk fibroin microcarrier loaded with clematis total saponins and chondrocytes on promoting rabbit knee articular cartilage defects repair

To prepare the silk fibroin microcarrier loaded with clematis total saponins (CTS) (CTS-silk fibroin microcarrier), and to investigate the effect of microcarrier combined with chondrocytes on promoting rabbit knee articular cartilage defects repair. CTS-silk fibroin microcarrier was prepared by high voltage electrostatic combined with freeze drying method using the mixture of 5% silk fibroin solution, 10 mg/mL CTS solution, and glycerin. The samples were characterized by scanning electron microscope and the cumulative release amount of CTS was detected. Meanwhile, unloaded silk fibroin microcarrier was also prepared. Chondrocytes were isolated from knee cartilage of 4-week-old New Zealand rabbits and cultured. The 3rd generation of chondrocytes were co-cultured with the two microcarriers respectively for 7 days in microgravity environment. During this period, the adhesion of chondrocytes to microcarriers was observed by inverted phase contrast microscope and scanning electron microscope, and the proliferation activity of cells was detected by cell counting kit 8 (CCK-8), and compared with normal cells. Thirty 3-month-old New Zealand rabbits were selected to make bilateral knee cartilage defects models and randomly divided into 3 groups ( n=20). Knee cartilage defects in group A were not treated, and in groups B and C were filled with the unloaded silk fibroin microcarrier-chondrocyte complexes and CTS-silk fibroin microcarrier-chondrocyte complexes, respectively. At 12 weeks after operation, the levels of matrix metalloproteinase 9 (MMP-9), MMP-13, and tissue inhibitor of MMP 1 (TIMP-1) in articular fluid were detected by ELISA. The cartilage defects were collected for gross observation and histological observation (HE staining and toluidine blue staining). Western blot was used to detect the expressions of collagen type Ⅱ and proteoglycan. The inflammatory of joint synovium was observed by histological staining and inducible nitric oxide synthase (iNOS) immunohistochemical staining. The CTS-silk fibroin microcarrier was spherical, with a diameter between 300 and 500 μm, a porous surface, and a porosity of 35.63%±3.51%. CTS could be released slowly in microcarrier for a long time. Under microgravity, the chondrocytes attached to the surface of the two microcarriers increased gradually with the extension of culture time, and the proliferation activity of chondrocytes at 24 hours after co-culture was significantly higher than that of normal chondrocytes ( P<0.05). There was no significant difference in proliferation activity of chondrocytes between the two microcarriers ( P>0.05). In vivo experiment in animals showed that the levels of MMP-9 and MMP-13 in group C were significantly lower than those in groups A and B ( P<0.05), and the level of TIMP-1 in group C was significantly higher ( P<0.05). Compared with group A, the cartilage defects in groups B and C were filled with repaired tissue, and the repaired surface of group C was more complete and better combined with the surrounding cartilage. Histological observation and Western blot analysis showed that the International Cartilage Repair Scoring (ICRS) and the relative expression levels of collagen type Ⅱ and proteoglycan in groups B and C were significantly better than those in group A, and group C was significantly better than group B ( P<0.05). The histological observation showed that the infiltration of synovial inflammatory cells and hyperplasia of small vessels significantly reduced in group C compared with groups A and B. iNOS immunohistochemical staining showed that the expression of iNOS in group C was significantly lower than that in groups A and B ( P<0.05). CTS-silk fibroin microcarrier has good CTS sustained release effect and biocompatibility, and can promote the repair of rabbit cartilage defect by carrying chondrocyte proliferation in microgravity environment.

Generation of hybrid tissue engineered construct through embedding autologous chondrocyte loaded platelet rich plasma/alginate based hydrogel in porous scaffold for cartilage regeneration

Over the past decades, various attempts have been made to develop suitable tissue-engineered constructs to repair or regenerate the damaged or diseased articular cartilage. In the present study, we embedded Platelet rich plasma (PRP)/Sodium Alginate (SA) based hydrogel in porous 3D scaffold of chitosan (CH)/chondroitin sulfate (CS)/silk fibroin (SF) to develop hybrid scaffold for cartilage tissue construct generation with abilities to support shape recovery potential, facilitate uniform cells distribution and mimic gel like cartilage tissue extracellular matrix.The developed hybrid matrix shows suitable pore size (55–261 μm), porosity (77 ± 4.3%) and compressive strength (0.13 ± 0.04 MPa) for cartilage tissue construct generation and its applications. The developed SA/PRP-based cartilage construct exhibits higher metabolic activity, glycosaminoglycan deposition, expression of collagen type II, and aggrecan in comparison to SA based cell-scaffold construct. In-vivo animal study was also performed to investigate the biocompatibility and cartilage tissue regeneration potential of the developed construct. The obtained gross analysis of knee sample, micro-computed tomography, and histological analysis suggest that implanted tissue construct possess the superior potential to regenerate hyaline cartilage defect of thickness around 1.10 ± 0.36 mm and integrate with surrounding tissue at the defect site. Thus, the proposed strategy for the development of cartilage tissue constructs might be beneficial for the repair of full-thickness knee articular cartilage defects.

Treatment of Traumatic Cartilage Defects of Rabbit Knee Joint by Adipose Derived Stem Cells Combined with Kartogenin Hydroxyapatite Nano-Microsphere Complex.

Kartogenin (KGN) can effectively promote the differentiation of adipose derived stem cells (ADSCs) into chondrocytes. With the help of three-dimensional slow-release technology, nano-microspheres are generated and used for cartilage repair. First, KGN solution was prepared, which was dissolved in distilled water, and NaOH solution, HEPES buffer, sodium chloride particles, and hydroxyapatite (HA) solution were added to prepare KGN-HA gel solution containing KGN. ADSCs were isolated from the posterior iliac of four-week-old New Zealand rabbits. After 0.5 mL of rabbit second-generation ADSCs suspension was taken, 2 mL KGN-HA gel solution was added, and they were mixed well to obtain ADSCs/KGN-HA gel. After drying treatment, ADSCs/KGN-HA nanospheres were precipitated. In the experiment, the minimum inhibitory concentration (MIC) of Staphylococcus aureus (MIC) > 2 μg/mL in each group of KGN-HA gel solution was reached within 30 days. Group K3 had the highest KGN encapsulation rate and the largest cumulative release. The biological activity of ADSCs was good in the ADSCs/KGN-HA nanoparticle solution. After two weeks of incubation, the nanospheres were positive for type II collagen staining/toluidine blue staining, that was, chondrocyte phenotype. The rabbit knee articular cartilage defect model was established. The defect part was filled with ADSCs/KGN-HA gel, which was similar in color to the surrounding tissues. The two sides of the tissue section and the surrounding cartilage tissue healed well, and no carrier material remained. Moreover, the cells were round, with cartilage lacuna formed around them, and after the simple periosteum was covered and repaired, the surface was sunken. The cell structure changed, and the healing with the surroundings was poor. In summary, under the slow release of KGN, ADSCs/KGN-HA nanospheres made ADSCs maintain a good biological form, which grew and proliferated normally. The ADSCs/KGN-HA nanoparticles cultured in vitro had a good repair effect on the animal model of articular cartilage defects.

Dry arthroscopy with a simple retraction technique for knee joint cartilage repair using allogenic human umbilical cord blood-derived mesenchymal stem cells

Mesenchymal stem cell treatment has become more widely available and has shown promising potential for the repair of knee articular cartilage defects. More recently, open arthrotomy has been performed via a para-patellar incision for cartilage repair using allogenic human umbilical cord blood-derived mesenchymal stem cells (hUCB-MSCs). However, arthroscopy allows better visualization and leads to earlier gain of the range of motion and less scar formation than open arthrotomy, especially in the knee joint. In this study, we present an easy and effective technique for arthroscopic hUCB-MSCs implantation without any special equipment.

Repairing of Subchondral Defect and Articular Cartilage of Knee Joint of Rabbit by Gadolinium Containing Bio-Nanocomposites

A variety of gadolinium (Gd) based nanoparticles (NPs) were synthesized due to the unique magnetic properties of Gd-containing rare earth compounds and the particularity of micro/nano-materials, which were then incorporated into hydroxyapatite (HA) to obtain inorganic-organic composite materials. Then, HA/Gd NPs containing slow-release transforming growth factor (TGF-β1) were harvested. Adipose-derived stem cells (ADSCs) were extracted from the adipose tissue of a four-month-old New Zealand white rabbit. HA/Gd NPs were attached to absorbable gelatin sponge to obtain HA/Gd NPs/gelatin sponge composite scaffold. In addition, the third generation ADSCs were taken and cultured in the composite scaffold, so that ADSCs-HA/Gd bio-nanocomposites were obtained. The in vitro culture test of osteoblast MC3T3-E1 showed that Gd-containing NPs had good biocompatibility. The prepared HA/Gd NPs loaded with TGF-β1 were spherical, with an average particle size of (9.16 ± 3.16) μm. The NPs were easy to aggregate and adherent. Enzyme-linked immunosorbent assay (ELISA) test results showed that TGF-β1 in NPs was sustained and released continuously for 29 days. HA/Gd NPs/gelatin sponge composite scaffold combined with ADSCs were co-cultured for three days, and the electron microscope showed that the HA/Gd NPs were dispersed, and the cells could adhere and grow well. Then, animal models of rabbit knee articular cartilage defects were established and were rolled into three groups (ADSCs-HA/Gd nano group, HA/Gd nano scaffold group, and blank control). The repair area of the rabbit knee of ADSCs-HA/Gd nano group was smooth and flat, the scaffold was absorbed, the toluidine blue stain was positive, and the type II collagen immunohistochemical stain was positive. In general, ADSCs-HA/Gd nanomaterials were helpful for chondrogenic cell differentiation and had certain adoption prospects in the field of tissue engineering to repair cartilage defects.

High kinesiophobia and pain catastrophizing in people with articular cartilage defects in the knee and associations with knee function

PurposeThe purpose of this study was to evaluate the extent to which individuals with knee articular cartilage defects (ACDs) have kinesiophobia and pain catastrophizing, and how these psychological factors relate to self-reported knee outcomes. MethodsThirty-five individuals seeking surgical consultation for an ACD in the knee confirmed with 3.0T MRI and 18 controls without history of knee injury participated in the study. Kinesiophobia was measured with the Tampa Scale of Kinesiophobia (TSK), and scored using the modified 11-item (TSK-11) methods. Pain catastrophizing was measured with the Pain Catastrophizing Scale (PCS). Data were analyzed using descriptive statistics, independent t-tests, chi-squared tests and Spearman’s correlation coefficients, as appropriate (α = 0.05). ResultsParticipants with ACDs reported higher TSK-11 scores (median 27 [IQR 25–29]) and higher PCS scores (median 10 [IQR 4–18]) than controls (median TSK-11 16 [IQR 14–17], p < 0.001; median PCS 0 [IQR 0–9], p < 0.001). Within those with knee ACDs, higher TSK-11 scores were associated with worse knee pain, function on activities of daily living, sports/recreation, and knee-related quality of life scores (rho = −0.38 to −0.61). Higher pain catastrophizing was associated with worse function with activities of daily living and knee-related quality of life (rho = −0.37 to −0.40). ConclusionsKinesiophobia and pain catastrophizing in people with knee ACDs were higher than controls. Higher kinesiophobia and pain catastrophizing were associated with worse function and quality of life. Further study of the impact of these psychological factors on outcomes and prognosis in people with knee ACDs is warranted.

Culture Time Needed to Scale up Infrapatellar Fat Pad Derived Stem Cells for Cartilage Regeneration: A Systematic Review.

Adipose tissue is a rich source of stem cells, which are reported to represent 2% of the stromal vascular fraction (SVF). The infrapatellar fat pad (IFP) is a unique source of tissue, from which human adipose-derived stem cells (hADSCs) have been shown to harbour high chondrogenic potential. This review aims to calculate, based on the literature, the culture time needed before an average knee articular cartilage defect can be treated using stem cells obtained from arthroscopically or openly harvested IFP. Firstly, a systematic literature review was performed to search for studies that included the number of stem cells isolated from the IFP. Subsequent analysis was conducted to identify the amount of IFP tissue harvestable, stem cell count and the overall yield based on the harvesting method. We then determined the minimum time required before treating an average-sized knee articular cartilage defect with IFP-derived hADSCs by using our newly devised equation. The amount of fat tissue, the SVF cell count and the stem cell yield are all lower in arthroscopically harvested IFP tissue compared to that collected using arthrotomy. As an extrapolation, we show that an average knee defect can be treated in 20 or 17 days using arthroscopically or openly harvested IFP-derived hADSCs, respectively. In summary, the systematic review conducted in this study reveals that there is a higher amount of fat tissue, SVF cell count and overall yield (cells/volume or cells/gram) associated with open (arthrotomy) compared to arthroscopic IFP harvest. In addition to these review findings, we demonstrate that our novel framework can give an indication about the culture time needed to scale up IFP-derived stem cells for the treatment of articular cartilage defects based on harvesting method.

Surgical Techniques for Knee Cartilage Repair: An Updated Large-Scale Systematic Review and Network Meta-analysis of Randomized Controlled Trials

The aim of this study was to investigate the most appropriate surgical interventions for patients with knee articular cartilage defects from the level I randomized clinical trials. We searched five databases for level I randomized clinical trials. Treatments were compared if reported in more than one study using network meta-analysis to boost the number of included studies per comparison. We studied 21 articles that included 891 patients. Traumatic lesion was the most common cause in the included patients. There were significantly higher failure rates in the microfracture (MF) group compared to autologous chondrocyte implantation (ACI) group at 10-year follow-up. Moreover, osteochondral autograft transplantation (OAT) showed significantly more excellent or good results at > 3-year follow-up compared to MF, whereas MF showed significantly more poor results versus ACI and matrix-induced autologous chondrocyte implantation (MACI). Furthermore, OAT showed significantly more poor results than MACI at 1-year follow-up. Similarly, patients who underwent OAT had higher return-to-activity rates than those with MF. It is noteworthy that the Knee injury and Osteoarthritis Outcome Score was higher in patients who underwent characterized chondrocyte implantation or MACI compared to MF. Finally, there were no significant differences among the various interventions regarding reintervention, biopsy types or adverse events. According to the P scores for interventions ranking, there was a disagreement concerning the best intervention; however, MF was always ranked as the last. Cartilage repair techniques, rather than MF, provide higher quality repair of tissue and have lower failure and higher return-to-activity rates. Moreover, OAT had significantly more excellent or good results compared to MF, whereas MF had significantly more poor results than ACI and MACI. Future studies need to have longer follow-up periods and more representative populations to investigate the efficacy and safety of these interventions. Level I: meta-analysis of Level I studies.

Clinical outcome after mosaicplasty of knee articular cartilage defects of patellofemoral joint versus tibiofemoral joint

BackgroundThe purpose was to investigate survival of cartilage repair in the knee joint by osteochondral autograft transfer stratified by location of the lesion; patellofemoral joint (N = 26) versus the medial or lateral femoral condyles (N = 58). MethodsFor survival analyses, “failure” was defined as the event of a patient reporting a poor Lysholm score (below 65 points) or undergoing a knee replacement procedure. ResultsThe survival distribution was not significantly different between the patellofemoral joint and the tibiofemoral joint groups. ConclusionsThe current study suggest that similar long-term outcome can be expected after OAT procedures for the patellofemoral or tibiofemoral joint. Level of evidenceTherapeutic study, Level III.

Decellularized cartilage matrix scaffolds with laser-machined micropores for cartilage regeneration and articular cartilage repair

Decellularized allogeneic and xenogeneic articular cartilage matrix scaffolds (CMS) are considered ideal scaffolds for cartilage regeneration owing to their heterogeneous architecture, and biochemical and biomechanical properties of native articular cartilage. However, the dense structure of the articular cartilage extracellular matrix, particularly the arrangement of collagen fibers, limits cellular infiltration, leading to poor cartilage regeneration. In addition, the incomplete removal of xenograft cells is associated with immunogenic reaction in the host. To facilitate the migration of chondrocytes into scaffolds and the rate of decellularization processing, we applied a carbon dioxide laser technique to modify the surface of porcine CMS while retaining major properties of the scaffold. By optimizing the laser parameters, we introduced orderly, lattice-arranged conical micropores of suitable depth and diameter onto the cartilage scaffold surface without affecting the cartilage shape or mechanical properties. We found that laser-modified CMS (LM-CMS) could enhance the degree of decellularization and were conducive to cell adhesion, as compared with the intact CMS. Decellularized scaffolds were seeded with rabbit-derived chondrocytes and cultured for 8 weeks in vitro. We found that cell-scaffold constructs formed cartilage-like tissue within the micropores and on the scaffold surface. In vivo, we found that cell-scaffold constructs subcutaneously implanted into the flanks of nude mice formed ivory-white neocartilage with high contents of DNA and cartilage matrix components, as well as good mechanical strength as compared with native CMS. Furthermore, scaffolds combined with autogenous chondrocytes induced neocartilage and better structural restoration at 8 weeks after transplantation into rabbit knee articular cartilage defects. In conclusion, decellularized xenogeneic CMS with laser-machined micropores offers an ideal scaffold with high fidelity for the functional reconstruction of articular cartilage.

Effects of Bakuchiol on chondrocyte proliferation via the PI3K-Akt and ERK1/2 pathways mediated by the estrogen receptor for promotion of the regeneration of knee articular cartilage defects.

ObjectivesCartilaginous tissue degradation occurs because of the lack of survival of chondrocytes. Here, we ascertained whether bakuchiol (BAK) has the capability of activating chondrocyte proliferation.Materials and methodsThe effect of BAK on the proliferation of rat chondrocytes at a concentration of 10 and 20 µmol/L was investigated. The molecular mechanisms involving target binding and signalling pathways were elucidated by RNA‐sequencing, qPCR, molecular docking and Western blotting. Matrigel mixed with bakuchiol was implanted locally into rat knee articular cartilage defects to verify the activation of chondrocytes due to bakuchiol in vivo.ResultsBakuchiol implantation resulted in the activation of rat chondrocyte proliferation in a dose‐dependent manner. RNA‐sequencing revealed 107 differentially expressed genes (DEGs) with 75 that were up‐regulated and 32 that were down‐regulated, indicating increased activation of the PI3K‐Akt and cell cycle pathways. Activation of the phosphorylation of Akt, ERK1/2 and their inhibitors blocked the proliferative effect of bakuchiol treatment, confirming its direct involvement in these signal transduction pathways. Molecular docking and siRNA silencing revealed that estrogen receptor‐α (ERα) was the target of bakuchiol in terms of its cell proliferative effect via PI3K activation. Two weeks after implantation of bakuchiol, the appearance and physiological structure of the articular cartilage was more integrated with abundant chondrocytes and cartilage matrix compared to that of the control.ConclusionsBakuchiol demonstrated significant bioactivity towards chondrocyte proliferation via the PI3K‐Akt and ERK1/2 pathways mediated by estrogen receptor activation and exhibited enhanced promotion of the remodelling of injured cartilage.