Cells, soluble factors and matrix harmonically play the concert of allograft integration.

Implantation of allograft tissues has massively grown over the last years, especially in the fields related to sports medicine. Beside the fact that often no autograft option exists, autograft related disadvantages as donor-site morbidity and prolonged operative time are drastically reduced with allograft tissues. Despite the well documented clinical success for bone allograft procedures, advances in tissue engineering raised the interest in meniscus, osteochondral and ligament/tendon allografts. Notably, their overall success rates are constantly higher than 80%, making them a valuable treatment option in orthopaedics, especially in knee surgery. Complications reported for allografting procedures are a small risk of disease transmission, immunologic rejection, and decreased biologic incorporation together with nonunion at the graft-host juncture and, rarely, massive allograft resorption. Although allografting is a successful procedure, improved techniques and biological knowledge to limit these pitfalls and maximize graft incorporation are needed. A basic understanding of the biologic processes that affect the donor-host interactions and eventual incorporation and remodelling of various allograft tissues is a fundamental prerequisite for their successful clinical use. Further, the importance of the interaction of immunologic factors with the biologic processes involved in allograft incorporation has yet to be fully dissected. Finally, new tissue engineering techniques and use of adjunctive growth factors, cell based and focused gene therapies may improve the quality and uniformity of clinical outcomes. The aim of this review is to shed light on the biology of meniscus, osteochondral and ligament/tendon allograft incorporation and how collection and storage techniques may affect graft stability and embodiment.Level of evidence V.

Comparison of calcimimetic R568 and calcitriol in mineral homeostasis in the Hyp mouse, a murine homolog of X-linked hypophosphatemia.

X-linked hypophosphatemia (XLH) caused by mutations in the Phex gene is the most common human inherited phosphate wasting disorder characterized by enhanced synthesis of fibroblast growth factor 23 (FGF23) in bone, renal phosphate wasting, 1,25(OH)2D3 (1,25D) deficiency, rickets and osteomalacia. Here we studied the effects of calcimimetic R568 and calcitriol treatment in the Hyp mouse, a murine homolog of XLH. We hypothesized that mineral homeostasis is differentially affected by R568 and 1,25D with respect to the PTH-vitamin D-FGF23-Klotho axis and bone health. Four-week-old male Hyp mice received R568 in different doses, 1,25D or vehicle for 28days. Vehicle-treated wild-type mice served as controls. Both R568 and 1,25D reduced PTH levels, yet only 1,25D raised serum phosphate levels in Hyp mice. 1,25D increased calciuria and further enhanced FGF23 synthesis in bone and circulating FGF23 levels. By contrast, R568 reduced bone FGF23 expression and serum total but not intact FGF23 concentrations. Renal 1,25D metabolism was further impaired by 1,25D and improved although not normalized by R568. Hyp mice showed reduced renal Klotho levels, which were increased by 1,25D and high dose R568. 1,25D, but not R568, significantly improved femur growth, and weight gain, and partially restored growth plate morphology and bone mineralization. Although a significant improvement of trabecular bone was noted by µCT, compared to 1,25D the effects of R568 on bone histomophometric parameters were marginal. Our data indicate that monotherapy with R568 reduced PTH and FGF23 synthesis in bone, but failed to restore vitamin D and phosphate metabolism and skeletal abnormalities in Hyp mice. By contrast, 1,25D improved body growth, and defective mineralization despite further enhancement of skeletal FGF23 synthesis thereby highlighting the importance of vitamin D in bone mineralization in Hyp mice.

Effect of supramalleolar varus and valgus deformities on the tibiotalar joint: a cadaveric study.

BACKGROUND: Distal tibia coronal plane malalignment predisposes the ankle joint to asymmetric load. The purpose of this cadaveric study was to quantify changes in pressure and force transfer in an ankle with a supramalleolar deformity. MATERIALS AND METHODS: Seventeen cadaveric lower legs were loaded with 700 N after creating supramalleolar varus and valgus deformities. The fibula was left intact in 11 specimens and osteotomized in six. Tekscan© sensors were used to measure the tibiotalar pressure characteristics. RESULTS: In isolated supramalleolar deformity, the center of force and peak pressure moved in an anteromedial direction for valgus and posterolateral direction for varus deformities. The change was in an anteromedial direction for varus and in a posterolateral direction for valgus deformities in specimens with an osteotomized fibula. CONCLUSION: Two essentially different groups of varus and valgus deformities of the ankle joint need to be distinguished. The first group is an isolated frontal plane deformity and the second group is a frontal plane deformity with associated incongruency of the ankle mortise. CLINICAL RELEVANCE: Our findings underline the complexity of asymmetric osteoarthritis of the ankle joint. In addition, results from this study provide useful information for future basic research on coronal plane deformity of the hindfoot and for determining appropriate surgical approaches.