Development and functional evaluation of a hyaluronic acid coated nano-formulation with kaempferol as a novel intra-articular agent for Knee Osteoarthritis treatment.

Knee osteoarthritis (OA) involves articular cartilage degradation driven mainly by inflammation. Kaempferol (KM), known for its anti-inflammatory property, holds potential for OA treatment. This study investigated the potential of hyaluronic acid (HA)-coated gelatin nanoparticles loaded with KM (HA-KM GNP) for treating knee OA. KM was encapsulated into gelatin nanoparticles (KM GNP) and then coated with HA to form HA-KM GNPs. Physical properties were characterized, and biocompatibility and cellular uptake were assessed in rat chondrocytes. Anti-inflammatory and chondrogenic properties were evaluated using IL-1ß-stimulated rat chondrocytes, compared with HA-coated nanoparticles without KM (HA GNP) and KM alone. Preclinical efficacy was tested in an anterior cruciate ligament transection (ACLT)-induced knee OA rat model treated with intra-articular injection of HA-KM GNP. Results show spherical HA-KM GNPs (88.62 ± 3.90 nm) with positive surface charge. Encapsulation efficiency was 98.34 % with a sustained release rate of 18 % over 48 h. Non-toxic KM concentration was 2.5 µg/mL. In IL-1ß-stimulated OA rat chondrocytes, HA-KM GNP significantly down-regulated RNA expression of IL-1ß, TNF-α, COX-2, MMP-9, and MMP-13, while up-regulating SOX9 compared to HA GNP, and KM. In vivo imaging demonstrated significantly higher fluorescence intensity within rat knee joints for 3 hours post HA-KM GNP injection compared with KM GNP (185.2% ± 34.1% vs. 45.0% ± 16.7%). HA-KM GNP demonstrated significant effectiveness in reducing subchondral sclerosis, attenuating inflammation, inhibiting matrix degradation, restoring cartilage thickness, and reducing the severity of OA in the ACLT rat model. In conclusion, HA-KM GNP holds promise for knee OA therapy.

Lovastatin impairs cellular proliferation and enhances hyaluronic acid production in fibroblast-like synoviocytes.

INTRODUCTION: Statins have demonstrated chondroprotective effects by reducing inflammation and mitigating extracellular matrix degradation. However, statins are also reported to be cytotoxic to several types of cells. Early-onset osteoarthritis (OA) is characterized by synovial inflammation, which adversely affects hyaluronan (HA) production in fibroblast-like synoviocytes (FLSs). Nevertheless, the precise effects of statins on the synovium remain unclear. METHODS: This study investigated the impact of lovastatin on human FLSs, and HA secretion-related genes, signaling pathways, and production were evaluated. RESULTS: The findings revealed that high doses of lovastatin (20 or 40 µM) decreased FLS viability and increased cell death. FLS proliferation ceased when cultured in a medium containing 5 or 10 µM lovastatin. mRNA expression analysis demonstrated that lovastatin (5 and 10 µM) upregulated the gene level of hyaluronan synthase 1 (HAS1), HAS2, and proteoglycan 4 (PRG4), but not HAS3. While the expression of multidrug resistance-associated protein 5 transporter gene remained unaffected, both inward-rectifying potassium channel and acid-sensing ion channel 3 were upregulated. Western blot further confirmed that lovastatin increased the production of HAS1 and PRG4, and activated the PKC-α, ERK1/2, and p38-MAPK signaling pathways. Additionally, lovastatin elevated intracellular cAMP levels and HA production in FLSs. CONCLUSION: Lovastatin impairs cellular proliferation but enhances HA production in human FLSs.

Current treatment concepts for Achilles tendon rupture.

Achilles tendon rupture is a common and primary cause of lower limb tendon injury suffered during sports-related activities. The causes of Achilles tendon rupture include the calf muscle and tendon overuse, poor tendon quality, and various medical conditions. Historically, acute Achilles tendon rupture was treated conservatively. However, historical techniques are now associated with an increased risk of rerupture. To address this problem, open repair has been proposed. Open repair is associated with a reduced risk of rerupture; however, it is also closely associated with wound complications, like wound infection, whose treatment is time-consuming and costly. Therefore, minimally invasive Achilles tendon repair has been proposed as a promising option with acceptable functional outcomes. Nevertheless, despite its benefits, minimally invasive Achilles tendon repair is associated with increased risks of sural nerve injury and rerupture. In this review, we evaluate the currently used treatment strategies for acute Achilles tendon rupture and their historical evolution to provide evidence-based recommendations for physicians.

Comparison of Knot-Tying Techniques During the Arthroscopic Broström-Gould Procedure: Semiconstrained Freehand Versus Knot Pusher Techniques.

Background: The arthroscopic Broström technique with or without Gould modification has been used to treat patients with anterior talofibular ligament injury who failed nonoperative management and progressed to chronic lateral ankle instability. However, some patients develop limited range of motion over the ankle joint postoperatively. Purpose/Hypothesis: To compare the clinical outcomes and midterm functional performance of knot-tying techniques between using a knot pusher and a semiconstrained freehand tie during arthroscopic Broström-Gould procedure with inferior extensor retinaculum (IER) augmentation. It was hypothesized that the semiconstrained freehand tie would provide better plantarflexion of the ankle joint compared with the knot pusher. Study Design: Cohort study; Level of evidence, 3. Methods: Included were 135 consecutive patients with mild-to-moderate lateral ankle instability (mean age, 42.7 years; range, 16-78 years) who underwent an arthroscopic Broström-Gould procedure from March 1, 2016, to April 30, 2022. The patients were divided into 2 groups according to the tying technique used in the Gould modification: surgical tie using a knot pusher (KP group; n = 30) or a semiconstrained freehand tie (FT group; n = 105). Radiographic parameters and ultrasound dynamic testing were examined during the preoperative assessment. Preoperative and 2-year postoperative assessments comprised American Orthopaedic Foot and Ankle Society Ankle-Hindfoot Scale, visual analog scale for pain, and 12-Item Short Form Survey (SF-12) scores. Results: The 2 groups had no differences in age, sex, or severity distribution in the preoperative assessment. American Orthopaedic Foot and Ankle Society Ankle-Hindfoot Scale, visual analog scale pain, and SF-12 scores were significantly better at the postoperative evaluation (all P < .05) in both groups. No significant difference was noted between groups in outcome scores. In the KP group, however, 7 out of 30 patients (23.3%) developed ankle stiffness with tightness when performing plantarflexion movement. No patients in the FT group reported similar symptoms. Conclusion: For mild-to-moderate chronic lateral ankle instability, we propose an arthroscopic Broström procedure with the addition of IER augmentation using a semiconstrained freehand tie to avoid overtightening the IER. This ensures favorable patient satisfaction and clinical outcomes without limitation of plantarflexion of the ankle joint and avoids the possible complication of stiffness with plantarflexion.

An in vitro analysis of the hemostatic efficacy of fibrinogen precipitation with varied keratin fraction compositions.

In preclinical studies, human hair has demonstrated effective hemostatic properties, potentially attributed to keratin proteins facilitating rapid conversion of fibrinogen to fibrin during coagulation. However, the rational use of human hair keratin for hemostasis remains unclear, given its complex mixture of proteins with diverse molecular weights and structures, leading to variable hemostatic capacity. To optimize the rational utilization of human hair keratin for hemostasis, we investigated the effects of different keratin fractions on keratin-mediated fibrinogen precipitation using a fibrin generation assay. Our study focused on high molecular weight keratin intermediate filaments (KIFs) and lower molecular weight keratin-associated proteins (KAPs) combined in various ratios during the fibrin generation. Scanning electron microscope analysis of the precipitates revealed a filamentous pattern with a broad distribution of fiber diameters, likely due to the diversity of keratin mixtures involved. An equal proportion of KIFs and KAPs in the mixture yielded the most extensive precipitation of soluble fibrinogen in an in vitro study, potentially due to structure-induced exposure of active sites. However, all hair protein samples exhibited diverse catalytic behaviors compared to thrombin, highlighting the potential of utilizing specific hair fractions to develop hair protein-based hemostatic materials with optimized capacity.

Bioinspired collagen-gelatin-hyaluronic acid-chondroitin sulfate tetra-copolymer scaffold biomimicking native cartilage extracellular matrix facilitates chondrogenesis of human synovium-derived stem cells.

The microenvironment plays a crucial role in stem cell differentiation, and a scaffold that mimics native cartilaginous extracellular components can promote chondrogenesis. In this study, a collagen-gelatin-hyaluronic acid-chondroitin sulfate tetra-copolymer scaffold with composition and architecture similar to those of hyaline cartilage was fabricated using a microfluidic technique and compared with a pure gelatin scaffold. The newly designed biomimetic scaffold had a swelling ratio of 1278 % ± 270 %, a porosity of 77.68 % ± 11.70 %, a compressive strength of 1005 ± 174 KPa, and showed a good resilience against compression force. Synovium-derived stem cells (SDSCs) seeded into the tetra-copolymer scaffold attached to the scaffold firmly and exhibited good mitochondrial activity, high cell survival with a pronounced glycosaminoglycan production. SDSCs cultured on the tetra-copolymer scaffold with chondrogenic induction exhibited upregulated mRNA expression of COL2A1, ChM-1, Nrf2, TGF-ß1, and BMP-7. Ex vivo study revealed that the SDSC-tetra-copolymer scaffold regenerated cartilage-like tissue in SCID mice with abundant type II collagen and S-100 production. BMP7 and COL2A1 expression in the tetra-copolymer scaffold group was much higher than that in the gelatin scaffold group ex vivo. The tetra-copolymer scaffold thus exhibits strong chondrogenic capability and will facilitate cartilage tissue engineering.

An assessment of physical properties and the viability of osteoblast-like cells of cefazolin-impregnated calcium sulfate bone-void filler.

Calcium sulfate, an injectable and biodegradable bone-void filler, is widely used in orthopedic surgery. Based on clinical experience, bone-defect substitutes can also serve as vehicles for the delivery of drugs, for example, antibiotics, to prevent or to treat infections such as osteomyelitis. However, antibiotic additions change the characteristics of calcium sulfate cement. Moreover, high-dose antibiotics may also be toxic to bony tissues. Accordingly, cefazolin at varying weight ratios was added to calcium sulfate samples and characterized in vitro. The results revealed that cefazolin changed the hydration reaction and prolonged the initial setting times of calcium sulfate bone cement. For the crystalline structure identification, X-ray diffractometer revealed that cefazolin additive resulted in the decrease of peak intensity corresponding to calcium sulfate dihydrate which implying incomplete phase conversion of calcium sulfate hemihydrate. In addition, scanning electron microscope inspection exhibited cefazolin changed the morphology and size of the crystals greatly. A relatively higher amount of cefazolin additive caused a faster degradation and a lower compressive strength of calcium sulfate compared with those of uploaded samples. Furthermore, the extract of cefazolin-impregnated calcium sulfate impaired cell viability, and caused the death of osteoblast-like cells. The results of this study revealed that the cefazolin additives prolonged setting time, impaired mechanical strength, accelerated degradation, and caused cytotoxicity of the calcium sulfate bone-void filler. The aforementioned concerns should be considered during intra-operative applications.

Chronic Lateral Ankle Instability Treated With Tendon Allografting: A Preliminary Comparison of Arthroscopic and Open Anatomic Ligament Reconstruction.

Background: Roughly 30% of patients with chronic lateral ankle instability (CLAI) have long-lasting painful instability requiring surgical intervention. Ligament reconstruction with the traditional open method and using tendon allografts can provide sufficient mechanical stability for severe CLAI. Arthroscopic ligament reconstruction with tendon allograft has recently been introduced to treat CLAI. Purpose: In this study, we describe an arthroscopic ligament reconstruction procedure involving the use of the tendon allograft for patients with CLAI, and we compare the efficacy of this procedure with open ligament reconstruction with tendon allograft. Study Design: Cohort study; Level of evidence, 3. Methods: We enrolled 10 patients (4 men and 6 women) with CLAI (mean age, 37.3 years; range, 16-57 years) who underwent arthroscopic ligament reconstruction with tendon allografting between November 2017 and June 2019. The control group consisted of 10 patients who received open tendon allograft reconstruction. Preoperative and 2-year postoperative functional outcomes were evaluated using the American Orthopaedic Foot & Ankle Society ankle-hindfoot scale (AOFAS), Karlsson Ankle Functional Score (KAFS), pain visual analog scale (VAS), 12-Item Short Form Health Survey (SF-12), and Tegner activity score (TAS). Results: The mean operative time was 118 and 110 minutes in the arthroscopic and open groups, respectively. At 2-year follow-up, scores on the AOFAS improved significantly compared with preoperatively, from 71.3 to 96.4 (P = .006) in the arthroscopic group, and from 68.6 to 96.7 (P = .005) in the open group. The postoperative AOFAS, VAS, KAFS, and SF-12 scores did not differ significantly between the 2 groups; however, the TAS score was significantly higher in the arthroscopic reconstruction group compared with in the open group (7 vs 6.1, respectively; P = .01). Conclusion: Arthroscopic ligament reconstruction with tendon allografting resulted in sufficient ankle stability and no donor-site morbidity. This procedure can yield similar functional outcomes to open reconstruction technique and may be an option for the management of CLAI.

Multilayer Electrospun-Aligned Fibroin/Gelatin Implant for Annulus Fibrosus Repair: An In Vitro and In Vivo Evaluation.

Annulus fibrosus (AF) damage is proven to prompt intervertebral disc (IVD) degeneration, and unrepaired AF lesions after surgical discectomy may boost herniation of the nucleus pulposus (NP) which may lead to further compression of neural structures. Moreover, vascular and neural ingrowth may occur within the defect which is known as a possible reason for discogenic pain. Due to a limited healing capacity, an effective strategy to repair and close the AF defect is necessary. In this study, using electrospinning technology, two nature polymers, silk fibroin and gelatin, were linked to imitate the unique lamellae structure of native AF. Our findings revealed that a multilayer electrospun-aligned fibroin/gelatin scaffold with mechanical and morphological properties mimicking those of native AF lamellae have been developed. The average diameter of the nanofiber is 162.9 ± 38.8 nm. The young's modulus is around 6.70 MPa with an ultimate tensile strength of around 1.81 MP along preferred orientation. The in vitro test confirmed its biocompatibility and ability to maintain cell viability and colonization. Using a porcine model, we demonstrated that the multilayer-aligned scaffold offered a crucial microenvironment to induce collagen fibrous tissue production within native AF defect. In the implant-repaired AF, H&E staining showed homogeneous fibroblast-like cell infiltration at the repaired defect with very little vascular ingrowth, which was confirmed by magnetic resonance imaging findings. Picrosirius red staining and immunohistochemical staining against type I collagen revealed positively stained fibrous tissue in an aligned pattern within the implant-integrated site. Relative to the intact control group, the disc height index of the serial X-ray decreased significantly in both the injury control and implant group at 4 weeks and 8 weeks (p < 0.05) which indicated this scaffold may not reverse the degenerative process. However, the results of the discography showed that the effectiveness of annulus repair of the implant group is much superior to that of the untreated group. The scaffold, composed with nature fibroin/gelatin polymers, could potentially enhance AF healing that could prevent IVD recurrent herniation, as well as neural and neovascular ingrowth after discectomy surgeries.

Surgical Reconstruction with Tendon Allografting Following Iatrogenic Rupture of the Plantar Fascia: A Case Report.

Plantar fasciitis is a common cause of heel pain, and the disorder is generally self-limiting after adequate conservative treatment. When conservative treatment is unsuccessful, surgical release is an effective treatment option. Here we report a case of iatrogenic plantar fascia rupture after surgical release for treatment of recalcitrant plantar fasciitis. Preoperative MRI revealed a 4.2 cm gap between the distal fascia stump and the calcaneal tuberosity in the sagittal view at 8 months post-injury. To circumvent the possibility of rupture site retear or poor tissue healing by direct repair, we used tendon allografting for the reconstruction of the chronic plantar fascia rupture. The patient gradually recovered after the surgery. Complications of plantar fascia rupture after surgical release is a potential risk but rarely observed. Chronic plantar fascia rupture with medial arch collapse is difficult to treat. We used a tendon allograft to reconstruct the plantar fascia, restoring its function and mechanical strength. After 5 years of follow-up, no complications were reported, and magnetic resonance imaging indicated the reconstructed plantar fascia tissue to be in good condition.

Binary colloidal crystals (BCCs) modulate the retina-related gene expression of hBMSCs - A preliminary study.

Surface topography-induced lineage commitment of human bone marrow stem cells (hBMSCs) has been reported. However, this effect on hBMSC differentiation toward retinal pigment epithelium (RPE)-like cells has not been explored. Herein, a family of cell culture substrates called binary colloidal crystals (BCCs) was used to stimulate hBMSCs into RPE-like cells without induction factors. Two BCCs, named SiPS (silica (Si)/polystyrene (PS)) and SiPSC (Si/carboxylated PS), having similar surface topographies but different surface chemistry was used for cell culture. The result showed that cell proliferation was no difference between the two BCCs and tissue culture polystyrene (TCPS) control. However, the cell attachment, spreading area, and aspect ratio between surfaces were significantly changed. For example, cells displayed more elongated on SiPS (aspect ratio ~7.0) than those on SiPSC and TCPS (~2.0). The size of focal adhesions on SiPSC (~1.6 µm2) was smaller than that on the TCPS (~2.5 µm2). qPCR results showed that hBMSCs expressed higher RPE progenitor genes (i.e., MITF and PAX6) on day 15, and mature RPE genes (i.e., CRALBP and RPE65) on day 30 on SiPS than TCPS. On the other hand, the expression of optical vesicle or neuroretina genes (i.e., MITF and VSX2) was upregulated on day 15 on SiPSC compared to the TCPS. This study reveals that hBMSCs could be modulated into different cell subtypes depending on the BCC combinations. This study shows the potential of BCCs in controlling stem cell differentiation.

Midterm outcomes of midfoot and hindfoot arthrodesis with strut allograft for Müller-Weiss disease.

BACKGROUND: Müller-Weiss disease (MWD), a rare dysplastic disorder of the foot, is characterized by deformity, sclerosis, and fragmentation of the lateral part of navicular bone. Arthrodesis is the mainstay treatment for MWD. Generally, arthrodesis can be achieved through internal fixation with metallic implants, and morselized chip bone may be packed into the gap for better bone union. However, with this procedure, the original foot size is not maintained and support for the foot arch is not provided. Sequela of short foot, or flatfoot is commonly observed even though these complications of surgery had not been reported with cases of MWD treated by arthrodesis. Herein, we present a retrospective analysis of treating MWD through midfoot and hindfoot arthrodesis combined with strut allograft. METHODS: From August 2006 to June 2019, 20 patients with MWD (mean age, 59.6 years; range, 40-80 years) underwent midfoot and hindfoot arthrodesis with strut bone allograft and were followed for at least 24 months. The patients were able to ambulate and participate in rehabilitation programs 3 months postoperatively. RESULTS: The used four radiographic parameters (Meary's angle in anteroposterior and lateral view, talonavicular coverage angle, calcaneal pitch) demonstrated significant differences (P < .05) preoperatively and postoperatively, but those between the postoperative values and the values at the last follow-up session did not, indicating that strut allograft was able to maintain normal alignment. The mean American Orthopaedic Foot & Ankle Society Ankle-Hindfoot scores at 2 years postoperatively revealed significant improvement from baseline, from 60.2 to 84.2 (P < .05). The 12-item Short Form Health Survey scores also improved significantly (P < .05). All patients reported substantial pain relief and exhibited improved functional outcomes and gait patterns. CONCLUSIONS: For advanced-stage MWD, arthrodesis with a precisely shaped, size-matched strut allograft provided strong support for biomechanical alignment and enhanced functional performance.

Enhancement of the anticoagulant capacity of polyvinyl chloride tubing for cardiopulmonary bypass circuit using aluminum oxide nanoscale coating applied through atomic layer deposition.

For cardiopulmonary bypass, the polyvinyl chloride (PVC) circuit which can initiate the activation of platelets and the coagulation cascade after blood cell contacting is the possible detrimental effect. Surface coating of the PVC tubing system can be an effective approach to enhance circuit's hemocompatibility. In this study, aluminum oxide (Al2 O3 ) thin films were deposited through thermal atomic layer deposition (T-ALD) or plasma-enhanced ALD (PE-ALD) on PVC samples, and the anticoagulation of the Al2 O3 -coated PVC samples was demonstrated. The results revealed that Al2 O3 deposition through ALD increased surface roughness, whereas T-ALD had a relative hydrophilicity compared with blank PVC and PE-ALD. Whole blood immersion tests showed that blood clots formed on blank PVC and that a large amount of red blood cells was found on PE-ALD substrates, whereas less blood cells were noted in T-ALD samples. Both T-ALD and PE-ALD Al2 O3 films did not cause activation of blood cells, as evidenced in CD3+ /CD4+ /CD8+ , CD61+ /CD62P+ , and CD45+ /CD42b+ populations. Analysis of serum coagulation factors showed that a lower amount of prothrombin was absorbed on T-ALD Al2 O3 samples than that on blank PVC. For albumin and fibrinogen immersion tests, immunostaining and scanning electron microscopy further revealed that a thin albumin layer was absorbed on T-ALD Al2 O3 substrates but not on PVC samples. This study revealed that deposition of Al2 O3 films by T-ALD can improve anticoagulation of the PVC tubing system.

Ex Vivo Expanded Circulating Tumor Cells for Clinical Anti-Cancer Drug Prediction in Patients with Head and Neck Cancer.

The advanced-stage head and neck cancer (HNC) patients respond poorly to platinum-based treatments. Thus, a reliable pretreatment method for evaluating platinum treatment response would improve therapeutic efficiency and outcomes. This study describes a novel strategy to predict clinical drug responses in HNC patients by using eSelect, a lab-developed biomimetic cell culture system, which enables us to perform ex vivo expansion and drug sensitivity profiling of circulating tumor cells (CTCs). Forty liquid biopsies were collected from HNC patients, and the CTCs were expanded ex vivo using the eSelect system within four weeks. Immunofluorescence staining confirmed that the CTC-derived organoids were positive for EpCAM and negative for CD45. Two illustrative cases present the potential of this strategy for evaluating treatment response. The statistical analysis confirmed that drug sensitivity in CTC-derived organoids was associated with a clinical response. The multivariant logistic regression model predicted that the treatment accuracy of chemotherapy responses achieved 93.75%, and the area under the curves (AUCs) of prediction models was 0.8841 in the whole dataset and 0.9167 in cisplatin specific dataset. In summary, cisplatin sensitivity profiles of patient-derived CTCs expanded ex vivo correlate with a clinical response to cisplatin treatment, and this can potentially underpin predictive assays to guide HNC treatments.

Current treatment concepts for osteochondral lesions of the talus.

Osteochondral lesions of the talus (OLT) are a well-known cause of ankle joint pain and can sometimes lead to instability. These lesions are not only confined to articular hyaline cartilage, they can also affect the subchondral bone at the weight-bearing aspect of the talar dome. Nonoperative treatment is the preferred option for small lesions, however surgical intervention is recommended for large lesions or those for which conservative treatment has failed. Microfracture, abrasion arthroplasty and multiple drilling are all classified as bone marrow stimulation procedures; they are used to try to recruit precursor cells for cartilage regeneration and are especially suitable for small OLT lesions. For large lesions, osteochondral autografting and allografting are better options to reconstruct the articular defect, as they have better contours and mechanical strength. When there is limited subchondral bone involvement in large lesions, cell-based therapies such as autogenous chondrocyte implantation, potentially combined with a biomaterial matrix, are a promising option and acceptable functional outcomes have been reported. To provide evidence-based recommendations for clinicians, this article evaluates the currently available treatment strategies for OLT and their evolution over the past few decades.

Antifibrotic Effect of Bletilla striata Polysaccharide-Resveratrol-Impregnated Dual-Layer Carboxymethyl Cellulose-Based Sponge for The Prevention of Epidural Fibrosis after Laminectomy.

The application of antifibrotic materials can alleviate epidural fibrosis by restricting excessive fibroblast proliferation and mitigating scar tissue formation. Here, a biodegradable carboxymethyl cellulose (CMC)-Bletilla striata polysaccharide (BSP)-resveratrol (RES) sponge was fabricated to inhibit scar tissue formation post laminectomy surgery. Fibroblasts NIH/3T3, myoblasts C2C12, neural cells PC-12, and Schwann cells RSC96 were used to evaluate the in vitro cytocompatibility. Laminectomies on 10 Sprague-Dawley rats with/without the application of the CMC-BSP-RES sponge were performed. The severity of adhesion between the dura mater and formed scar tissue was qualitatively scored. All cell lines exhibited good viability with no significant difference in cytotoxicity when cultured with variable extractions of the CMC-BSP-RES sponge. S100a4 and P4hb expressions were downregulated in NIH/3T3 cultured in the CMC-BSP-RES sponge, implying that this sponge potentially inhibits fibroblast activity. No post-operative shrinkage or dura mater expansion along the surgical site was detected. The peel-off tests revealed that the tenacity of adhesion de-creased. Histopathological examinations verified that the average number of fibroblasts in the CMC-BSP-RES group considerably decreased. The CMC-BSP-RES sponge is a biocompatible and effective material for alleviating post-operative epidural fibrosis and mitigating fibroblast expression following laminectomy.

Silymarin modulates catabolic cytokine expression through Sirt1 and SOX9 in human articular chondrocytes.

BACKGROUND: Silymarin (SMN), a polyphenolic flavonoid, is involved in multiple bioactive functions including anti-inflammation. Pretreatment with SMN demonstrated chondroprotection against tumour necrosis factor-alpha (TNF-α) stimulation in a chondrocyte cell line. However, pre- and posttreatment with phytochemicals have varying effects on osteoarthritis (OA) chondrocytes, and the therapeutic potential of SMN after catabolic cytokine stimulation is not fully elucidated. METHODS: The cytotoxicity of SMN (12.5, 25, 50 and 100 µM) was evaluated in human primary chondrocytes. The chondrocytes were supplemented with SMN (25 and 50 µM) after interleukin-1beta (IL-1ß) stimulation. The mRNA expression and protein production of catabolic/anabolic cytokines as well as extracellular matrix (ECM) components were evaluated. RESULTS: High-dose SMN (100 µM) impaired the mitochondrial activity in chondrocytes, and 50 µM SMN further caused cell death in IL-1ß-stimulated cells. The addition of 25 µM SMN ameliorated cell senescence; downregulated the catabolic genes of inducible nitric oxide synthase, IL-1ß, TNF-α, matrix metalloproteinase-3 (MMP-3), MMP-9 and MMP-13; upregulated the anabolic genes of tissue inhibitor of metalloproteinase-1 (TIMP-1) and collagen type II alpha 1; and restored the expression of chondrogenic phenotype genes SOX9 and sirtuin-1 (Sirt1). In addition, the production of IL-1ß, MMP-3 and MMP-9 decreased with an increase in TIMP-1 secretion. However, the mRNA levels of IL-6, IL-8 and IL-10 and protein production remained high. The addition of nicotinamide, a Sirt1 inhibitor, downregulated SOX9 and attenuated the therapeutic effects of SMN on IL-1ß-stimulated chondrocytes. CONCLUSION: SMN regulates the chondrocyte phenotype through Sirt1 and SOX9 to improve ECM homeostasis and may serve as a complementary therapy for early-stage knee OA.

Infrapatellar Fat Pads-Derived Stem Cell Is a Favorable Cell Source for Articular Cartilage Tissue Engineering: An In Vitro and Ex Vivo Study Based on 3D Organized Self-Assembled Biomimetic Scaffold.

OBJECTIVE: Adipose tissue-derived stem cells (ASCs) are a promising source of cells for articular cartilage regeneration. However, ASCs isolated from different adipose tissue depots have heterogeneous cell characterizations and differentiation potential when cultured in 3-dimensional (3D) niches. DESIGN: We compared the chondrogenicity of ASCs isolated from infrapatellar fat pads (IPFPs) and subcutaneous fat pads (SCFPs) in 3D gelatin-based biomimetic matrix. RESULTS: The IPFP-ASC-differentiated chondrocytes had higher ACAN, COL2A1, COL10, SOX6, SOX9, ChM-1, and MIA-3 mRNA levels and lower COL1A1 and VEGF levels than the SCFP-ASCs in 3D matrix. The difference in mRNA profile may have contributed to activation of the Akt, p38, RhoA, and JNK signaling pathways in the IPFP-ASCs. The chondrocytes differentiated from IPFP-ASCs had pronounced glycosaminoglycan and collagen type II production and a high chondroitin-6-sulfate/chondroitin-4-sulfate ratio with less polymerization of ß-actin filaments. In an ex vivo mice model, magnetic resonance imaging revealed a shorter T2 relaxation time, indicating that more abundant extracellular matrix was secreted in the IPFP-ASC-matrix group. Histological examinations revealed that the IPFP-ASC matrix had higher chondrogenic efficacy of new cartilaginous tissue generation as evident in collagen type II and S-100 staining. Conclusion. ASCs isolated from IPFPs may be better candidates for cartilage regeneration, highlighting the translational potential of cartilage tissue engineering using the IPFP-ASC matrix technique.

Ultrasonography-Guided Minimally Invasive Surgery for Achilles Sleeve Avulsions.

BACKGROUND: Achilles sleeve avulsion, a relatively rare disorder, is characterized by sleeve-shaped injury extending from the calcaneus, located near the tendon insertion site. Unlike midsubstance tears of the Achilles tendon, end-to-end repair is difficult because less soft tissue is preserved distally. Open repair with transosseous sutures or suture anchors is currently favored. The purpose of this study was to evaluate the technical feasibility and functional outcomes of ultrasonography-guided Achilles sleeve avulsion repair. METHODS: From November 2009 to April 2018, 21 patients with Achilles sleeve avulsions (mean age, 57.8 years; range, 25-82 years) who underwent repair by the same surgeon were retrospectively reviewed. The repair was achieved through a stab wound under ultrasonographic guidance. Two parallel Bunnell-type sutures were crossed over the proximal stump and tied with sutures from suture anchors fixed in the calcaneal tuberosity. RESULTS: The mean operative time was 44 minutes, and the mean wound size was 1.5 cm. The patients were allowed to walk freely on postoperative week 6 with using high-ankle shoes. At postoperative 2 years' follow-up, the American Orthopaedic Foot & Ankle Society score significantly improved from 70.9 to 97.1 (P < .05); similarly, their 12-item Short Form Health Survey scores improved significantly (P < .05). Only 2 patients had superficial wound infections, which resolved with wound care and oral antibiotics. CONCLUSION: Our ultrasonography-guided surgical technique for Achilles sleeve avulsions provided excellent soft tissue visualization and availability as well as minimized the wound length to achieve good postsurgical outcomes. LEVEL OF EVIDENCE: Level IV, retrospective case series.

Midterm Results of Fresh-Frozen Osteochondral Allografting for Osteochondral Lesions of the Talus.

BACKGROUND: Osteochondral lesions of the talus (OLT) are relatively common. Following the failure of conservative treatment, many operative options have yielded varied results. In this study, midterm outcomes after fresh-frozen osteochondral allograft transplantation for the treatment of OLT were evaluated. METHODS: Twenty-five patients (12 women and 13 men) with a mean age 40.4 (range 18-70) years between 2009 and 2014 were enrolled. Of 25 ankles, 3, 13, 4, and 4 were involved with the talus at Raikin zone 3, 4, 6, and 7 as well as one coexisted with zone 4 and 6 lesion. The mean OLT area was 1.82 cm2 (range, 1.1-3.0). The mean follow-up period was 5.5 years (range, 4-9.3). Outcomes evaluation included the American Orthopaedic Foot & Ankle Society (AOFAS) ankle-hindfoot score, visual analog scale score, and 12-item Short Form Health Survey (SF-12). RESULT: AOFAS ankle-hindfoot score increased from 74 preoperatively to 94 at 2 years postoperatively (P < .001) and the SF-12 physical health component scores increased from 32 to 46 points (P < .001). Incorporation was inspected in all patients in the latest follow-up, and graft subsidence and radiolucency were observed in 2 and 7 cases, respectively, whereas graft collapse and revision OLT graft were not observed. Bone sclerosis was found in 6 of 25 patients. CONCLUSION: With respect to midterm results, fresh, frozen-stored allograft transplantation might be an option in the management of symptomatic OLT. LEVEL OF EVIDENCE: Level IV, retrospective case series.