Functional tissue engineering of ligament healing

Ligaments and tendons are dense connective tissues that are important in transmitting forces and facilitate joint articulation in the musculoskeletal system. Their injury frequency is high especially for those that are functional important, like the anterior cruciate ligament (ACL) and medial collateral ligament (MCL) of the knee as well as the glenohumeral ligaments and the rotator cuff tendons of the shoulder. Because the healing responses are different in these ligaments and tendons after injury, the consequences and treatments are tissue- and site-specific. In this review, we will elaborate on the injuries of the knee ligaments as well as using functional tissue engineering (FTE) approaches to improve their healing. Specifically, the ACL of knee has limited capability to heal, and results of non-surgical management of its midsubstance rupture have been poor. Consequently, surgical reconstruction of the ACL is regularly performed to gain knee stability. However, the long-term results are not satisfactory besides the numerous complications accompanied with the surgeries. With the rapid development of FTE, there is a renewed interest in revisiting ACL healing. Approaches such as using growth factors, stem cells and scaffolds have been widely investigated. In this article, the biology of normal and healing ligaments is first reviewed, followed by a discussion on the issues related to the treatment of ACL injuries. Afterwards, current promising FTE methods are presented for the treatment of ligament injuries, including the use of growth factors, gene delivery, and cell therapy with a particular emphasis on the use of ECM bioscaffolds. The challenging areas are listed in the future direction that suggests where collection of energy could be placed in order to restore the injured ligaments and tendons structurally and functionally

Role of biomechanics in the understanding of normal, injured, and healing ligaments and tendons

Ligaments and tendons are soft connective tissues which serve essential roles for biomechanical function of the musculoskeletal system by stabilizing and guiding the motion of diarthrodial joints. Nevertheless, these tissues are frequently injured due to repetition and overuse as well as quick cutting motions that involve acceleration and deceleration. These injuries often upset this balance between mobility and stability of the joint which causes damage to other soft tissues manifested as pain and other morbidity, such as osteoarthritis

Time to Switch to Second-line Antiretroviral Therapy in Children With Human Immunodeficiency Virus in Europe and Thailand.

Background: Data on durability of first-line antiretroviral therapy (ART) in children with human immunodeficiency virus (HIV) are limited. We assessed time to switch to second-line therapy in 16 European countries and Thailand. Methods: Children aged <18 years initiating combination ART (≥2 nucleoside reverse transcriptase inhibitors [NRTIs] plus nonnucleoside reverse transcriptase inhibitor [NNRTI] or boosted protease inhibitor [PI]) were included. Switch to second-line was defined as (i) change across drug class (PI to NNRTI or vice versa) or within PI class plus change of ≥1 NRTI; (ii) change from single to dual PI; or (iii) addition of a new drug class. Cumulative incidence of switch was calculated with death and loss to follow-up as competing risks. Results: Of 3668 children included, median age at ART initiation was 6.1 (interquartile range (IQR), 1.7-10.5) years. Initial regimens were 32% PI based, 34% nevirapine (NVP) based, and 33% efavirenz based. Median duration of follow-up was 5.4 (IQR, 2.9-8.3) years. Cumulative incidence of switch at 5 years was 21% (95% confidence interval, 20%-23%), with significant regional variations. Median time to switch was 30 (IQR, 16-58) months; two-thirds of switches were related to treatment failure. In multivariable analysis, older age, severe immunosuppression and higher viral load (VL) at ART start, and NVP-based initial regimens were associated with increased risk of switch. Conclusions: One in 5 children switched to a second-line regimen by 5 years of ART, with two-thirds failure related. Advanced HIV, older age, and NVP-based regimens were associated with increased risk of switch

Cemented all polyethylene tibial insert unicompartimental knee arthroplasty: A long term follow-up study

Unicompartimental knee arthroplasty outcome is sometimes compared to total knee arthroplasty but various implant parameters might greatly influence this outcome. The objectives of this study were to report the results of a consecutive series of 172 all-polyethylene unicompartmental knee arthroplasties (UKAs) and to detail possible factors of success and failure. HYPOTHESIS: It is possible to outline implant and technique factors determining success or failure in unicompartimental knee arthroplasty. MATERIALS AND METHODS: One hundred seventy-two HLS-type cemented resurfacing UKAs, with the femoral implant made of chrome-cobalt and the tibial implant tibial entirely in polyethylene (without anchorage studs) were consecutively implanted between 1988 and 2004 in 134 patients (111 females and 23 males) in our center according to the indications established in 1988, using the same technique for each surgery. The patients' mean age was 72.2 years (range, 25-90 years). The review rate was 83.7% (144 UKAs), with a mean follow-up of 62.3 months (range, 24-160 months). The series included 84 medial UKAs and 60 lateral UKAs. The clinical data were analyzed using the IKS criteria and the patients had a complete radiological evaluation before surgery and at the last follow-up. RESULTS: The rate of satisfied or very satisfied patients was 97.2%. No pain or slight pain was found in 81% of the cases. The mean flexion was 133 degrees (range, 85-150 degrees). The mean knee score varied from 63.6 before surgery to 91.5 (90.4 for medial UKAs and 92.9 for lateral UKAs) and the function score from 63.6 to 83.8 (84.7 for medial UKAs and 82.6 for lateral UKAs). The mean range of motion was 133 degrees (range, 85-150 degrees), better than the medial UKAs for osteonecrosis. The mean residual deformity was 4 degrees varus for the medial UKAs and 2 degrees valgus for the lateral UKAs. A radiolucency was found in 23% of the cases (20% tibial and 3% femoral), nonprogressive in all cases. In 87.2% of the cases, the opposite femorotibial compartment remained radiologically normal. No progression to osteoarthritis in the femoropatellar joint required additional surgery. Sixteen patients required revision surgery: in six cases, the implant was removed and a total prosthesis implanted (one late infection, one case of involvement of the opposite compartment, and four cases of tibial component loosening). In the other cases, one tibial baseplate was changed, five arthroscopies were done, and four unicompartmental knee replacements were done on the opposite compartment. The Kaplan-Meier survival rate (taking into account the revisions with implant change) was 95.6. The results of this series were very satisfactory and were similar to recent series in the world literature that showed survival rates between 90 and 98% at 10 years, rates that are equivalent to those found for total knee replacements. The mean flexion range of motion found was higher than the majority of other recent series, probably because of the precise patient selection in the present study, a minimally invasive approach, and the femoral implant design with an ascending condylar posterior cut. The deterioration of the contralateral compartment is frequently reported, but was perhaps prevented by the absence of overcorrection and patient selection. In this series, none of the UKAs was revised for wear. We explain this by the systematic preservation of a moderate undercorrection, particularly for medial UKAs, the quality of the polyethylene, and a selection based on patient weight and age. CONCLUSIONS: The option of an all-polyethylene tibial implant, with minimal bone cuts (femoral resurfacing), makes excellent long-term results possible