Summary. Silver nanoparticles improve the tensile property of the repaired Achilles tendon by modulating the synthesis and deposition of collagen. This makes silver nanoparticles a potential drug for tendon healing process with less undesirable side effect. Introduction. Tendon injury is a common injury that usually takes a long time to fully recover and often lead to problems of joint stiffness and re-rupture due to tissue adhesions and scarring on the repaired tendon respectively. Recently, it has been proven that silver nanoparticles (AgNPs) are capable of regenerating skin tissue with minimal scarring and comparable tensile property to normal skin. Hence, it is hypothesised that AgNPs could also improve the healing in tendon injury as both tissues are predominating with fibroblasts. The objective of this study is to look at the in vitro response of primary tenocytes to AgNPs and to investigate the mechanical and histological outcome in vivo. Methods and Materials. Primary tenocytes were harvested from 4 weeks old Sprague Dawley rat. 1.5×10. 4. cells per cm. 2. were seeded in triplicate for BrdU incorporation assay and Sirius red/ fast green staining to study the proliferation and collagen synthesis respectively. In vivo rat Achilles tendon injury model was used to investigate the effect of AgNPs to tendon regeneration. Briefly, the Achilles tendon was transected at 0.5cm from its insertion. The wound was either treated with 1mM AgNPs every 5 days or left untreated as the control. Skin incision was done without transecting the tendon in the sham group. The tendons were harvested on day 42 post operation. Tensile test and immunohistological staining on 7μm cryosections were performed to assess the mechanical property and biological events in healing respectively. SHG imaging was used to determine the collagen fibre orientation and abundance. Results. In vitro BrdU incorporation and Sirius red fast green assay suggested that AgNPs promoted the proliferation and collagen synthesis of tenocytes between 1 to 20μM and 10 to 20μM respectively. Tensile test on in vivo tissue showed that AgNPs-treated samples had significantly better tensile modulus compared to the untreated ones (p<0.05). SHG imaging suggested a better collagen alignment and density in AgNPs-treated samples. Immunohistochemistry demonstrated that AgNPs suppressed tumor necrosis factor (TNF α) whilst promoted fibromodulin (Fmod) and proliferating cell nucleus antigen (PCNA) expression. Discussion. Collagen is the major component that contributes to the tensile strength of a tendon. Its thickness, abundance and alignment directly affect the strength. In this study, it is found that AgNPs stimulate cell proliferation both in vitro and in vivo which is believed to be the reason of the increase in collagen synthesis. Fmod is an important proteoglycan responsible for collagen fibrillogenesis and TNF α is related to ECM degradation which directly affects collagen integrity. Stimulation of Fmod and alleviation of TNF α therefore promote collagen maturity and integrity which attributes to the improvement in the tensile property of the regenerated tissue. Furthermore, inflammation is known to relate to fibrosis and scarring in healing of many types of tissue. It is therefore postulated that the anti-inflammatory effect of AgNPs is one of the major reasons for this phenomenal healing of tendon. To conclude, this study demonstrates a positive effect of AgNPs to the early events of tendon healing which is important for accelerating the whole healing process and shortening of rehabilitation time

Objectives

Adult mice lacking the transcription factor NFAT1 exhibit osteoarthritis (OA). The precise molecular mechanism for NFAT1 deficiency-induced osteoarthritic cartilage degradation remains to be clarified. This study aimed to investigate if NFAT1 protects articular cartilage (AC) against OA by directly regulating the transcription of specific catabolic and anabolic genes in articular chondrocytes.

Bone marrow mesenchymal stromal cells were aspirated from immature male green fluorescent protein transgenic rats and cultured in a monolayer. Four weeks after the creation of the osteochondral defect, the rats were divided into three groups of 18: the control group, treated with an intra-articular injection of phosphate-buffered saline only; the drilling group, treated with an intra-articular injection of phosphate-buffered saline with a bone marrow-stimulating procedure; and the bone marrow mesenchymal stromal cells group, treated with an intra-articular injection of bone marrow mesenchymal stromal cells plus a bone marrow-stimulating procedure. The rats were then killed at 4, 8 and 12 weeks after treatment and examined.

The histological scores were significantly better in the bone marrow mesenchymal stromal cells group than in the control and drilling groups at all time points (p < 0.05). The fluorescence of the green fluorescent protein-positive cells could be observed in specimens four weeks after treatment.

Objectives

After an injury, the biological reattachment of tendon to bone is a challenge because healing takes place between a soft (tendon) and a hard (bone) tissue. Even after healing, the transition zone in the enthesis is not completely regenerated, making it susceptible to re-injury. In this study, we aimed to regenerate Achilles tendon entheses (ATEs) in wounded rats using a combination of kartogenin (KGN) and platelet-rich plasma (PRP).

Short intense electrical pulses transiently increase the permeability of the cell membrane, an effect known as electroporation. This can be combined with antiblastic drugs for ablation of tumours of the skin and subcutaneous tissue. The aim of this study was to test the efficacy of electroporation when applied to bone and to understand whether the presence of mineralised trabeculae would affect the capability of the electric field to porate the membrane of bone cells.

Different levels of electrical field were applied to the femoral bone of rabbits. The field distribution and modelling were simulated by computer. Specimens of bone from treated and control rabbits were obtained for histology, histomorphometry and biomechanical testing.

After seven days, the area of ablation had increased in line with the number of pulses and/or with the amplitude of the electrical field applied. The osteogenic activity in the ablated area had recovered by 30 days. Biomechanical testing showed structural integrity of the bone at both times.

Electroporation using the appropriate combination of voltage and pulses induced ablation of bone cells without affecting the recovery of osteogenic activity. It can be an effective treatment in bone and when used in combination with drugs, an option for the treatment of metastases.