Chondrocyte Response to Fresh Autologous Conditioned Serum Versus Freeze-Dried Allogenic Conditioned Serum.

OBJECTIVE: To investigate the cytokine release profile and histological response of human cartilage after exposure to autologous conditioned serum (ACS) and freeze-dried allogenic conditioned serum (FD-CS). DESIGN: Cartilage explants were collected from 6 patients undergoing total knee arthroplasty. ACS and FD-CS were created from patient serum samples. Cartilage samples were divided into 6 groups: (1) untreated control, (2) ACS, (3) FD-CS, (4) untreated interleukin (IL)-1ß (5 ng/ml), (5) IL-1ß + ACS, and (6) IL-1ß + FD-CS. After 12 days, cartilage samples were analyzed with glycosaminoglycan (GAG) concentration normalized to wet weight while comparing cytokine concentrations, and histological scoring. RESULTS: There was a significant decrease in pathology scoring for ACS (P = 0.0368) and FD-CS (P = 0.0368) in the IL-1ß injury groups compared with the untreated IL-1ß insult group. ACS and FD-CS significantly mitigate the IL-1ß induced increase in basic fibroblast growth factor (bFGF) (P = 0.0009 and P = 0.0002, respectively). FD-CS showed a significant decrease in IL-1ß concentration in the presence of IL-1ß insult compared with the untreated IL-1ß group (P < 0.0001). ACS-treated samples had significantly higher concentration of tumor necrosis factor (TNF)-α independent of IL-1ß when compared with samples not treated with biologics (P = 0.0053). CONCLUSIONS: Explanted osteoarthritic cartilage responds favorably and equivalently to treatment with ACS and FD-CS from a histological perspective. Both ACS and FD-CS were able to mitigate the IL-1ß-induced increases in bFGF and FD-CS lowered IL-1ß concentration while increasing interleukin-1 receptor antagonist (IL-1Ra) concentration. Although the cytokine profile of cartilage tissue explants treated with FD-CS appears to be different than that of ACS, this difference does not seem to affect biologic activity of FD-CS.

Evaluating the protective effect of dapsone on experimental osteoarthritis models induced by MIA in male rats.

OBJECTIVES: Osteoarthritis, a degenerative condition that results in significant morbidity, is typically managed with treatments aimed at symptom relief rather than addressing the underlying degeneration. Dapsone, recognized for its anti-inflammatory, antioxidant, antiexcitotoxic, and antiapoptotic properties, has demonstrated promising effects in various neurodegenerative diseases. This study explores the potential of dapsone to mitigate articular destruction, inflammation, and pain in rat models of osteoarthritis. METHODS: Osteoarthritis was induced in rats by injecting MIA into the right knee joint. Dapsone was then administered intraperitoneally at 5, 10, or 20 mg/kg every 2 days for 2 weeks. Behavioural tests were done on days 0, 7, and 14. On day 14, the articular cartilage was histologically analysed using H&E staining. Serum levels of NF-kB, IL-1ß, and TNF-α were evaluated by ELISA. RESULTS: Dapsone effectively reduces pain, inflammation, and articular cartilage damage in osteoarthritis. Specifically, it improves mechanical allodynia and thermal hyperalgesia, reduces inflammatory markers (TNF-α, IL-1ß, and NF-κB), and protects against cartilage destruction and chondrocyte loss, with the most significant effects at 20 mg/kg. CONCLUSIONS: Dapsone effectively prevents pain, inflammation, and cartilage damage in osteoarthritis rats, suggesting its potential as a therapeutic option for managing osteoarthritis.

Cartilage lacuna-biomimetic hydrogel microspheres endowed with integrated biological signal boost endogenous articular cartilage regeneration.

Despite numerous studies on chondrogenesis, the repair of cartilage-particularly the reconstruction of cartilage lacunae through an all-in-one advanced drug delivery system remains limited. In this study, we developed a cartilage lacuna-like hydrogel microsphere system endowed with integrated biological signals, enabling sequential immunomodulation and endogenous articular cartilage regeneration. We first integrated the chondrogenic growth factor transforming growth factor-ß3 (TGF-ß3) into mesoporous silica nanoparticles (MSNs). Then, TGF-ß3@MSNs and insulin-like growth factor 1 (IGF-1) were encapsulated within microspheres made of polydopamine (pDA). In the final step, growth factor-loaded MSN@pDA and a chitosan (CS) hydrogel containing platelet-derived growth factor-BB (PDGF-BB) were blended to produce growth factors loaded composite microspheres (GFs@µS) using microfluidic technology. The presence of pDA reduced the initial acute inflammatory response, and the early, robust release of PDGF-BB aided in attracting endogenous stem cells. Over the subsequent weeks, the continuous release of IGF-1 and TGF-ß3 amplified chondrogenesis and matrix formation. µS were incorporated into an acellular cartilage extracellular matrix (ACECM) and combined with a polydopamine-modified polycaprolactone (PCL) structure to produce a tissue-engineered scaffold that mimicked the structure of the cartilage lacunae evenly distributed in the cartilage matrix, resulting in enhanced cartilage repair and patellar cartilage protection. This research provides a strategic pathway for optimizing growth factor delivery and ensuring prolonged microenvironmental remodeling, leading to efficient articular cartilage regeneration.

PLCγ1 deficiency in chondrocytes accelerates the age-related changes in articular cartilage and subchondral bone.

Ageing is the most prominent risk for osteoarthritis (OA) development. This study aimed to investigate the role of phosphoinositide-specific phospholipase Cγ (PLCγ) 1, previously linked to OA progression, in regulating age-related changes in articular cartilage and subchondral bone. d-galactose (d-Gal) was employed to treat chondrocytes from rats and mice or injected intraperitoneally into C57BL/6 mice. RTCA, qPCR, Western blot and immunohistochemistry assays were used to evaluate cell proliferation, matrix synthesis, senescence genes and senescence-associated secretory phenotype, along with PLCγ1 expression. Subchondral bone morphology was assessed through micro-CT. In mice with chondrocyte-specific Plcg1 deficiency (Plcg1flox/flox; Col2a1-CreERT), articular cartilage and subchondral bone were examined over different survival periods. Our results showed that d-Gal induced chondrocyte senescence, expedited articular cartilage ageing and caused subchondral bone abnormalities. In d-Gal-induced chondrocytes, diminished PLCγ1 expression was observed, and its further inhibition by U73122 exacerbated chondrocyte senescence. Plcg1flox/flox; Col2a1-CreERT mice exhibited more pronounced age-related changes in articular cartilage and subchondral bone compared to Plcg1flox/flox mice. Therefore, not only does d-Gal induce senescence in chondrocytes and age-related changes in articular cartilage and subchondral bone, as well as diminished PLCγ1 expression, but PLCγ1 deficiency in chondrocytes may also accelerate age-related changes in articular cartilage and subchondral bone. PLCγ1 may be a promising therapeutic target for mitigating age-related changes in joint tissue.

Evaluation of the therapeutic potential of infrapatellar fat pad adipose-derived stem cells and their secretome for regenerating knee articular cartilage in a rat model of osteoarthritis.

Background: Mesenchymal stem cell (MSC) therapy has ameliorative effects for treating knee osteoarthritis (KOA) disease. Moreover, there is a growing interest in using MSCs-derived secretome (Sec) containing trophic factors secreted by MSCs for KOA treatment. Recently, some studies have suggested that the combination of MSCs and Sec has the potential to treat the diseases. Aims: This study aimed to evaluate the ameliorative effects of combined administration of infrapatellar fat pad (IPFP)-derived MSCs, a type of adipose-derived stem cells (ASCs), for treating degenerated cartilage in a rat model of KOA. Methods: IPFP-ASCs were isolated from the IPFP of male rats. Sec was obtained from IPFP-ASCs in the fourth passage. Eight weeks after the induction of KOA by collagenase II, the rats were divided into 5 groups (n=5), including a control group with no treatment, and four experimental groups that received sodium hyaluronate (Hyalgan®, Hya), ASCs, Sec, and IPFP-ASCs+Sec, respectively by an infrapatellar injection. To perform the pathological and radiological evaluations, the animals were sacrificed 8 weeks later. Results: Our findings indicated that combined administration of the IPFP-ASCs and Sec statistically (P<0.05) improved scores of medial tibial and femoral condyles and medial fabella osteophytes. Also, it statistically (P<0.05) enhances the cartilage surface, matrix, cell distribution and population viability, and subchondral bone indices. No statistical difference was observed between IPFP-ASCs+Sec and IPFP-ASCs. Conclusion: Administration of IPFP-ASCs+Sec has a therapeutic potential to treat KOA in rats. However, there is no difference in the combined administration of IPFP-ASCs and Sec with IPFP-ASCs alone.

Development of scaffold-free tissue-engineered constructs derived from mesenchymal stem cells with serum-free media for cartilage repair and long-term preservation.

Synovial mesenchymal stem cells (sMSCs) have great potential for cartilage repair, but their therapeutic design to avoid adverse effects associated with unknown factors remains a challenge. In addition, because long-term preservation is indispensable to maintain high quality levels until implantation, it is necessary to reduce their fluctuations. This study aimed to investigate the properties and feasibility of novel scaffold-free tissue-engineered constructs using serum-free media and to develop long-term preservation methods. sMSCs were cultured in serum-free media, seeded at high density in a monolayer, and finally developed as a sheet-like construct called "gMSC1". The properties of frozen gMSC1 (Fro-gMSC1) were compared with those of refrigerated gMSC1 (Ref-gMSC1) and then examined by their profile. Chondrogenic differentiation potential was analyzed by quantitative real-time polymerase chain reaction and quantification of glycosaminoglycan content. Xenografts into the cartilage defect model in rats were evaluated by histological staining. gMSC1 showed nearly similar properties independent of the preservation conditions. The animal experiment demonstrated that the defect could be filled with cartilage-like tissue with good integration to the adjacent tissue, suggesting that gMSC1 was formed and replaced the cartilage. Furthermore, several chondrogenesis-related factors were significantly secreted inside and outside gMSC1. Morphological analysis of Fro-gMSC1 revealed comparable quality levels to those of fresh gMSC1. Thus, if cryopreserved, gMSC1, with no complicated materials or processes, could have sustained cartilage repair capacity. gMSC1 is a prominent candidate in novel clinical practice for cartilage repair, allowing for large quantities to be manufactured at one time and preserved for a long term by freezing. Supplementary Information: The online version contains supplementary material available at 10.1007/s10616-024-00637-y.

The relationship between metabolite mediated immune regulatory imbalance and the occurrence of malignant tumors of bone and articular cartilage: a Mendelian randomization study.

Background: This study aims to assess the causal relationship between immune cell characteristics and malignant tumors of bone and articular cartilage, focusing on the mediating role of metabolites. Using Mendelian randomization, we evaluated these relationships based on genetic variations to identify potential biomarkers and therapeutic targets. Methods: A two-sample Mendelian randomization analysis was conducted using GWAS data for immune cell features and 1,400 metabolites to investigate direct and mediating effects. Effective instrumental variables (IVs) were selected, and statistical analyses-including inverse variance weighting (IVW), weighted median, and mode-based methods-were performed using R software. This approach enabled the assessment of direct causal relationships as well as the potential mediating role of metabolites in the association between immune cell features and malignancies. Results: Significant causal relationships were identified between 26 immune phenotypes and the risk of malignant tumors of bone and articular cartilage. Notably, the HLA DR+ NK cell phenotype SSC-A showed a positive correlation with the risk of these malignancies. Further analysis revealed causal relationships with 67 metabolites, 38 of which were positively correlated and 29 negatively correlated. Mediation analysis highlighted the role of immune surveillance and metabolic dysregulation in tumor development, as evidenced by the association between the immune phenotype SSC-A on HLA DR+ NK cells and the metabolite 5-hydroxyhexanoate. Conclusion: The findings suggest significant causal relationships between immune phenotypes and malignant tumors of bone and articular cartilage, with metabolites potentially mediating these relationships. These insights lay the groundwork for further research and could contribute to the development of new biomarkers and treatment strategies.

A Preliminary Study of Quantitative MRI Cartilage Loss Fraction and Its Association With Future Arthroplasty Using the Osteoarthritis Initiative Database.

Background and objective  Osteoarthritis (OA) is the most common arthritis in the world. Despite the high disease burden, there is no therapy to prevent, halt, or reverse OA, and many clinical trials relied on radiographic biomarkers for therapy response. It is important to identify patients with early OA who will eventually need arthroplasty, the end-stage treatment for osteoarthritis. This pilot study evaluates a novel MRI biomarker, cartilage loss fraction, for association with future arthroplasty and evaluates its feasibility of use and effect size estimates. Materials and methods Publicly available knee MRIs from the Osteoarthritis Initiative were used. A total of 38 participants with Kellgren-Lawrence (K-L) grade >1 and 38 participants with K-L grade ≤ 1 at enrollment were matched in age, sex, race, and BMI, and assessed for the degree of full-thickness cartilage loss, or cartilage loss fraction. Univariate conditional logistic regression analysis was performed for differences in cartilage loss fractions between groups. Receiver operating characteristic (ROC) curve analysis was performed to assess the association of MRI biomarkers and knee arthroplasty during the eight-year follow-up. Results The medial femoral condyle, medial tibial plateau, total, and two-year progression cartilage loss fractions were significantly higher in participants with K-L grade >1 (p < 0.01 for all) and showed high area under the curve (AUC) values on ROC analysis (812, 0.827, 0.917, and 0.933, respectively). These results were comparable or more strongly associated with other OA grading schemes. Conclusion MRI biomarker cartilage loss fractions are significantly higher in subjects with K-L grade >1 and show a strong association with arthroplasty. After further validation, cartilage loss fracture may be used to predict future arthroplasty.

Study on ultrasound-enhanced molecular transport in articular cartilage.

Local intra-articular administration with minimal side effects and rapid efficacy is a promising strategy for treating osteoarthritis(OA). Most drugs are rapidly cleared from the joint space by capillaries and lymphatic vessels before free diffusion into cartilage. Ultrasound, as a non-invasive therapy, enhances molecular transport within cartilage through the mechanisms of microbubble cavitation and thermal effects. This study investigated the mass transfer behavior of solute molecules with different molecular weights (479 Da, 40 kDa, 150 kDa) within porcine articular cartilage under low-frequency ultrasound conditions of 40 kHz and ultrasound intensities of 0.189 W/cm2 and 0.359 W/cm2. The results revealed that under the conditions of 0.189 W/cm2 ultrasound intensity, the mass transfer concentration of solute molecules were higher compared to passive diffusion, and with an increase in ultrasound intensity to 0.359 W/cm2, the mass transfer effect within the cartilage was further enhanced. Ultrasound promotes molecular transport in different layers of cartilage. Under static conditions, after 2 h of mass transfer, the concentration of small molecules in the superficial layer is lower than that in the middle layer. After applying ultrasound at 0.189 W/cm2, the molecular concentration in the superficial layer significantly increases. Under conditions of 0.359 W/cm2, after 12 h of mass transfer, the concentration of medium and large molecules in the deep layer region increased by more than two times. In addition, this study conducted an assessment of damage to porcine articular cartilage under ultrasound exposure, revealing the significant potential of low-frequency, low-intensity ultrasound in drug delivery and treatment of OA.

Endogenous Tissue Engineering for Chondral and Osteochondral Regeneration: Strategies and Mechanisms.

Increasing attention has been paid to the development of effective strategies for articular cartilage (AC) and osteochondral (OC) regeneration due to their limited self-reparative capacities and the shortage of timely and appropriate clinical treatments. Traditional cell-dependent tissue engineering faces various challenges such as restricted cell sources, phenotypic alterations, and immune rejection. In contrast, endogenous tissue engineering represents a promising alternative, leveraging acellular biomaterials to guide endogenous cells to the injury site and stimulate their intrinsic regenerative potential. This review provides a comprehensive overview of recent advancements in endogenous tissue engineering strategies for AC and OC regeneration, with a focus on the tissue engineering triad comprising endogenous stem/progenitor cells (ESPCs), scaffolds, and biomolecules. Multiple types of ESPCs present within the AC and OC microenvironment, including bone marrow-derived mesenchymal stem cells (BMSCs), adipose-derived mesenchymal stem cells (AD-MSCs), synovial membrane-derived mesenchymal stem cells (SM-MSCs), and AC-derived stem/progenitor cells (CSPCs), exhibit the ability to migrate toward injury sites and demonstrate pro-regenerative properties. The fabrication and characteristics of scaffolds in various formats including hydrogels, porous sponges, electrospun fibers, particles, films, multilayer scaffolds, bioceramics, and bioglass, highlighting their suitability for AC and OC repair, are systemically summarized. Furthermore, the review emphasizes the pivotal role of biomolecules in facilitating ESPCs migration, adhesion, chondrogenesis, osteogenesis, as well as regulating inflammation, aging, and hypertrophy-critical processes for endogenous AC and OC regeneration. Insights into the applications of endogenous tissue engineering strategies for in vivo AC and OC regeneration are provided along with a discussion on future perspectives to enhance regenerative outcomes.

Disentangling the detrimental effects of local from systemic adipose tissue dysfunction on articular cartilage in the knee.

OBJECTIVE: Obesity increases osteoarthritis (OA) risk due to adipose tissue dysfunction with associated metabolic syndrome and excess weight. Lipodystrophy syndromes exhibit systemic metabolic and inflammatory abnormalities similar to obesity without biomechanical overloading. Here, we used lipodystrophy mouse models to investigate the effects of systemic versus intra-articular adipose tissue dysfunction on the knee. METHODS: Intra-articular adipose tissue development was studied using reporter mice. Mice with selective lipodystrophy of intra-articular adipose tissue were generated by conditional knockout (cKO) of Bscl2 in Gdf5-lineage cells, and compared with congenital Bscl2 knockout (KO) mice with generalised lipodystrophy and associated systemic metabolic dysfunction. OA was induced by surgically destabilising the medial meniscus (DMM) and obesity by high-fat diet (HFD). Gene expression was analysed by quantitative RT-PCR and tissues were analysed histologically. RESULTS: The infrapatellar fat pad (IFP), in contrast to overlying subcutaneous adipose tissue, developed from a template established from the Gdf5-expressing joint interzone during late embryogenesis, and was populated shortly after birth by adipocytes stochastically arising from Pdgfrα+ Gdf5-lineage progenitors. While female Bscl2 KO mice with generalised lipodystrophy developed spontaneous knee cartilage damage, Bscl2 cKO mice with intra-articular lipodystrophy did not, despite synovial hyperplasia and inflammation of the residual IFP. Furthermore, male Bscl2 cKO mice showed no worse cartilage damage after DMM. However, female Bscl2 cKO mice with intra-articular lipodystrophy showed increased susceptibility to the cartilage-damaging effects of HFD-induced obesity. CONCLUSION: Our findings emphasise the prevalent role of systemic metabolic and inflammatory effects in impairing cartilage homeostasis, with a modulatory role for intra-articular adipose tissue.

Articular Surface Damage Following Headless Intramedullary Nail Fixation of Proximal Phalanx Fractures.

PURPOSE: Offering the benefits of rigid fixation while minimizing soft tissue dissection, intramedullary implants have become a popular choice among hand surgeons. Their placement often requires traversing or passing in proximity to joint surfaces. This study aimed to assess the damage to the articular cartilage of the base of the proximal phalanx resulting from antegrade placement of threaded headless intramedullary nails. METHODS: A cadaveric study comparing two techniques for antegrade placement of threaded headless intramedullary nails was conducted in 56 digits. The first entailed a single 2.1 mm intramedullary nail placed via the dorsal base of the proximal phalanx, whereas the second used two 1.8 mm intramedullary nails inserted via the collateral recesses of the phalangeal base. All specimens were analyzed for articular surface damage with the cartilage defect measured as a percentage of total joint surface area. Damage to the extensor tendons was also assessed in a subset of specimens. RESULTS: No significant difference in the percentage of articular surface damage was observed, with an average 3.21% ± 2.34% defect in the single 2.1 mm nail group and a 2.71% ± 3.42% mean defect in the two 1.8 mm nails group. There was no articular surface injury in 18% of digits in each group. Damage to extensor tendons was seen in three (9.4%) specimens and in all cases involved either the extensor indicis proprius or extensor digiti minimi. CONCLUSIONS: Hardware insertion using either the dorsal base of the proximal phalanx or the collateral recesses of the phalangeal base both demonstrated minimal articular cartilage damage and infrequent injury to the extensor tendons. CLINICAL RELEVANCE: With proper technique for antegrade insertion into the proximal phalanx, the cartilage defect observed often encompasses only a small percentage of the overall joint surface area.

In situ study on articular cartilage degeneration in simulated microgravity by HOF-ATR-FTIR spectroscopy.

Fourier transform infrared spectroscopy (FTIRS) can provide rich information on the composition and content of samples, enabling the detection of subtle changes in tissue composition and structure. This study represents the first application of FTIRS to investigate cartilage under microgravity. Simulated microgravity cartilage model was firstly established by tail-suspension (TS) for 7, 14 and 21 days, which would be compared to control samples. A self-developed hollow optical fiber attenuated total reflection (HOF-ATR) probe coupled with a FTIR spectrometer was used for the spectral acquisition of cartilage samples in situ, and one-way analysis of variance (ANOVA) was employed to analyze the changes in the contents of cartilage matrix at different stages. The results indicate that cartilage degenerates in microgravity, the collagen content gradually decreases with the TS time, and the structure of collagen fibers changes. The trends of proteoglycan content and collagen integrity show an initial decrease followed by an increase, ultimately significantly decreasing. The findings provide the basis for the cartilage degeneration in microgravity with TS time, which must be of real significance for space science and health detection.

[Tanshinone â ¡A Ameliorates Cartilage Degeneration in Ovariectomized Rats by Regulating TGF-ß1/Smad2/MMPs Signaling Pathway]. / ä¸¹å‚é ®â ¡A通过调节TGF-ß1/Smad2/MMPsä¿¡å·é€šè·¯æ”¹å–„åµå·¢æ‘˜é™¤å¤§é¼ å ³èŠ‚è½¯éª¨é€€è¡Œæ€§æ”¹å˜.

Objective: To investigate the ameliorative effect of tanshinone ⅡA (Tan) on osteoarticular degeneration in ovariectomized rats (a postmenopausal estrogen deficiency model) and the mechanisms involved. Methods: Eight-week-old female Sprague Dawley (SD) rats were randomly allocated to 5 groups (n=10 each), including a Sham operation group (Sham), an ovariectomy group (OVX), and low, medium, and high-dose Tan groups. Eight weeks after bilateral ovariectomy, the rats in the low, medium, and high-dose Tan groups were treated with Tan at the doses of 5, 10, and 20 mg/kg for a duration of 28 days. Evaluation of the rat articular cartilage was performed using X-ray imaging, anatomical observation, hematoxylin and eosin (H&E) staining, and toluidine blue staining. Immunohistochemistry was performed to assess the expression levels of transforming growth factor ß1 (TGF-ß1), phosphorylated-smad2 (p-Smad2), type Ⅱ collagen (CⅡ), matrix metalloproteinase 9 (MMP-9), and MMP-13 in the cartilage tissue. Results: The knee joints of the OVX rats exhibited narrowed joint spaces, osteophyte formation, cartilage erosion or even localized cartilage cracks, faded methylene blue staining on the cartilage surface, disordered arrangement of chondrocytes, unclear or interrupted tidal line, and increased Kellgren-Lawrence grading, Pelletier grading, Mankin grading, and OARSI scores compared to those of the Sham group (P<0.01), as revealed by X-ray imaging, anatomical observation, and histological examination results. Tan ameliorated the degenerative changes in the knee joint caused by OVX in a dose-dependent manner while improving Kellgren-Lawrence grading, Pelletier grading, Mankin grading, and OARSI scores. Immunohistochemistry findings showed that TGF-ß1, p-Smad2, and CⅡ expression levels were significantly increased (P<0.01), while MMP-9 and MMP-13 expression levels were significantly decreased (P<0.01) in the articular cartilage of the Tan group compared to those of the OVX group, with all these effects being dose-dependent. Conclusion: Tan mitigates articular cartilage degeneration in ovariectomized rats, which may be related to the regulation of TGF-ß1/Smad2/MMPs signaling pathway.

Prognostic Factors on Preoperative MRI for Patient-Reported Outcomes After Posterior Medial Meniscus Root Repair.

Background: Repair of posterior medial meniscus root (PMMR) tears has demonstrated favorable outcomes and may prevent rapid progression of knee osteoarthritis; however, there is a paucity of data regarding prognostic factors affecting postoperative outcomes. Purpose/Hypothesis: The purpose of this study was to identify factors on preoperative magnetic resonance imaging (MRI) that predict postoperative outcomes after PMMR repair. It was hypothesized that patients with increasing levels of degenerative changes as evaluated through semiquantitative preoperative MRI scans would have worse postoperative patient-reported outcome (PRO) scores. Study Design: Cohort study; Level of evidence, 3. Methods: Patients who underwent PMMR repair between 2012 and 2020 and had minimum 2-year follow-up data were enrolled. Pre- and postoperative visual analog scale pain scores and postoperative PRO surveys including the Patient-Reported Outcomes Measurement Information System-Physical Function, Lysholm knee score, and Knee injury and Osteoarthritis Outcome Score (KOOS) were collected. Patients who achieved the Patient Acceptable Symptom State (PASS) on the KOOS subscales were reported. Two fellowship-trained musculoskeletal radiologists reviewed preoperative MRIs and calculated the Whole-Organ Magnetic Resonance Imaging Score for meniscus, cartilage, bone marrow edema-like lesions (BMELL), and meniscal extrusion. Statistical analysis was performed using the 2-sample t test, Mann-Whitney test, and Fisher exact test for categorical variables. Results: A total of 29 knees in 29 patients were evaluated (22 female, 7 male; mean age at surgery, 52.3 ± 9.9 years; body mass index, 27.6 ± 5.6 kg/m2; mean follow-up, 59.6 ± 26.5 months). Visual analog scale for pain scores decreased significantly from preoperatively (4.9 ± 2.0) to final follow-up (1.6 ± 1.9) (P < .001), and the percentage of patients meeting the PASS ranged from 44.8% for KOOS Sport and Recreation to 72.4% for KOOS Pain and KOOS Quality of Life. Patients with medial tibial BMELL (MT-BMELL) had significantly lower KOOS Symptoms scores (76.1 ± 17.3 vs 88.4 ± 9.7 without MT-BMELL; P = .032). Cartilage quality and presence of meniscal extrusion were not associated with outcomes. Conclusion: Patients with MT-BMELL on their preoperative MRI in the setting of PMMR tear were found to have worse KOOS Symptoms scores after PMMR repair.

Osteochondral Allograft Reaming Significantly Affects Chondrocyte Viability.

BACKGROUND: Chondrocyte viability is associated with the clinical success of osteochondral allograft (OCA) transplantation. PURPOSE: To investigate the effect of distal femoral OCA plug harvest and recipient site preparation on regional cell viability using traditional handheld saline irrigation versus saline submersion. STUDY DESIGN: Controlled laboratory study. METHODS: For each of 13 femoral hemicondyles, 4 cartilage samples were harvested: (1) 5-mm control cartilage, (2) 15-mm OCA donor plug harvested with a powered coring reamer and concurrent handheld saline irrigation ("traditional"), (3) 15-mm OCA donor plug harvested while submerged under normal saline ("submerged"), and (4) 5-mm cartilage from the peripheral rim of a recipient socket created with a 15-mm cannulated counterbore reamer to a total depth of 7 mm with concurrent handheld saline irrigation ("recipient"). The 15 mm-diameter plugs were divided into the central 5 mm and the peripheral 5 mm (2 edges) for comparisons. Samples were stained using calcein and ethidium, and live/dead cell percentages were calculated and compared across groups. RESULTS: Compared with the submerged group, the traditional group had significantly lower percentages of live cells across the whole plug (71.54% ± 4.82% vs 61.42% ± 4.98%, respectively; P = .003), at the center of the plug (72.76% ± 5.87% vs 62.30% ± 6.11%, respectively; P = .005), and at the periphery of the plug (70.93% ± 4.51% vs 60.91% ± 4.75%, respectively; P = .003). The traditional group had significantly fewer live cells in all plug regions compared with the control group (77.51% ± 9.23%; P < .0001). There were no significant differences in cell viability between the control and submerged groups (whole: P = .590; center: P = .713; periphery: P = .799). There were no differences between the central and peripheral 5-mm plug regions for the traditional (62.30% ± 6.11% vs 60.91% ± 4.75%, respectively; P = .108) and submerged (72.76% ± 5.87% vs 70.93% ± 4.51%, respectively; P = .061) groups. The recipient group (61.10% ± 5.02%) had significantly lower cell viability compared with the control group (P < .0001) and the periphery of the submerged group (P = .009) but was equivalent to the periphery of the traditional group (P = .990). CONCLUSION: There was a significant amount of chondrocyte death induced by OCA donor plug harvesting using a powered coring reamer with traditional handheld saline irrigation, which was mitigated by harvesting the plug while the allograft was submerged under saline. CLINICAL RELEVANCE: Mitigating this thermally induced damage by harvesting the OCA plug while the allograft was submerged in saline maintained chondrocyte viability throughout the plug and may help to improve the integration and survival of OCAs.

A genetic algorithm optimization framework for the characterization of hyper-viscoelastic materials: application to human articular cartilage.

This study aims to develop an automated framework for the characterization of materials which are both hyper-elastic and viscoelastic. This has been evaluated using human articular cartilage (AC). AC (26 tissue samples from 5 femoral heads) underwent dynamic mechanical analysis with a frequency sweep from 1 to 90 Hz. The conversion from a frequency- to time-domain hyper-viscoelastic material model was approximated using a modular framework design where finite element analysis was automated, and a genetic algorithm and interior point technique were employed to solve and optimize the material approximations. Three orders of approximation for the Prony series were evaluated at N = 1, 3 and 5 for 20 and 50 iterations of a genetic cycle. This was repeated for 30 simulations of six combinations of the above all with randomly generated initialization points. There was a difference between N = 1 and N = 3/5 of approximately ~5% in terms of the error estimated. During unloading the opposite was seen with a 10% error difference between N = 5 and 1. A reduction of ~1% parameter error was found when the number of generations increased from 20 to 50. In conclusion, the framework has proved effective in characterizing human AC.

An accelerated PETALUTE MRI sequence for in vivo quantification of sodium content in human articular cartilage at 3T.

OBJECTIVE: In this work, we evaluate the sodium magnetic resonance imaging (MRI) capabilities of a three-dimensional (3D) dual-echo ultrashort echo time (UTE) sequence with a novel rosette petal trajectory (PETALUTE), in comparison to the 3D density-adapted (DA) radial spokes UTE sequence in human articular cartilage in the knee. MATERIALS AND METHODS: We scanned five healthy subjects using a 3D dual-echo PETALUTE acquisition and two comparable implementations of 3D DA-radial spokes acquisitions, one matching the number of k-space projections (Radial - Matched Spokes) and the other matching the total number of samples (Radial - Matched Samples) acquired in k-space. RESULTS: The PETALUTE acquisition enabled equivalent sodium quantification in articular cartilage volumes of interest (168.8 ± 29.9 mM, mean ± standard deviation) to those derived from the 3D radial acquisitions (171.62 ± 28.7 mM and 149.8 ± 22.2 mM, respectively). We achieved a 41% shorter scan time of 2:06 for 3D PETALUTE, compared to 3:36 for 3D radial acquisitions. We also evaluated the feasibility of further acceleration of the PETALUTE sequence through retrospective compressed sensing with 2 × and 4 × acceleration of the first echo and showed structural similarity of 0.89 ± 0.03 and 0.87 ± 0.03 when compared to non-retrospectively accelerated reconstruction. CONCLUSION: We demonstrate improved scan time with equivalent performance using a 3D dual-echo PETALUTE sequence compared to the 3D DA-radial sequence for sodium MRI of articular cartilage.

Higher association of articular surface destruction with rheumatoid forefoot deformity arising from dislocation of the metatarsophalangeal joints in the lateral column.

BACKGROUND: To evaluate the relationship between the pattern and severity of metatarsophalangeal (MTP) joint dislocation in the lesser toes and severity of joint destruction in rheumatoid forefoot deformities. METHODS: Participants comprised of 13 patients (16 feet) who underwent resection arthroplasty of the metatarsal head of the lesser toes for rheumatoid arthritis of the MTP joints. Correlations between preoperative radiographic findings and histological grades second to fifth metatarsal heads taken intraoperatively were analyzed. RESULTS: In 62 metatarsal heads, complete dislocation of the MTP joint in the lesser toes significantly resulted in severe joint destruction compared to mild or moderate dislocation (P < 0.05). The proportion of severe cartilage damage in MTP joints with complete dislocation was 100 % in the 5th MTP joint, 83.3 % in the 4th MTP joint, and 58.3 % in the 2nd and 3rd MTP joints. Moreover, complete dislocation of the MTP joints in the lateral column showed the most severe joint destruction compared to that in the medial column (P = 0.03). CONCLUSION: Complete dislocation of the MTP joint in the lateral column is related to joint destruction in rheumatoid forefoot deformities.

Chondroprotection of articular cartilage integrity: Utilizing ultrasonic scalpel and hyperosmolar irrigation solution during cutting.

Objectives: Ultrasonic (US) cutting of cartilage in orthopaedic surgery has received little attention despite its potential to reduce chondrocyte death which could enhance cartilage repair. We aimed to investigate whether an ultrasonically-vibrating scalpel to cut human articular cartilage could reduce chondrocyte death, and to determine if hyper-osmolarity could provide chondroprotection during the procedure. Methods: A scalpel (no. 15) was mounted on an ultrasonic transducer to resonate at 35 â€‹kHz with 30 â€‹µm vibrational displacement. Thirty-six fresh human femoral cartilage samples were divided into four groups based on ultrasonic activation (US or non-US) and saline osmolarity (300 or 600 mOsm/L). Cell viability was assessed using a live/dead cell assay and analysed quantitatively by confocal microscopy. Histology illustrated tissue surface changes at the cut site. Results: The overall chondrocyte death percentage at both the US and non-US cut sites showed comparable results (p â€‹> â€‹0.05) in both osmolarities. However, the zone of chondrocyte death was reduced by 31 â€‹± â€‹5% and 36 â€‹± â€‹6%, respectively, when comparing US cutting at 300 mOsm/L and 600 mOsm/L to the control group (non-US cutting; 300 mOsm/L) (p â€‹< â€‹0.05). The width of the cut was consistent at both sites, regardless of the method of cutting. Conclusion: Cutting human cartilage with US in the presence of 300 or 600 mOsm/L media was chondroprotective compared to normal (non-US) scalpel cutting in 300 mOsm/L medium. These results suggest chondroprotection can be achieved while cutting using a US scalpel and raised osmolarity, potentially improving cartilage regeneration and repair following injury.