Osteonecrosis with the use of polymethylmethacrylate cement for hip replacement: thermal-induced damage evidenced in vivo by decreased osteocyte viability.

Thermal damage to host bone is a possible source of compromise of fixation in patients undergoing cemented total hip replacement (THR). Data on the subject to date are derived from mathematical modelling powered by animal studies. The aim of this study was to assess the effect of cement thickness on osteocyte viability in a population of patients undergoing cemented THR. An in vivo model was designed and validated by means of a finite element analysis. During standard hip joint replacement in 14 patients, the femoral necks were exposed before final resection to the heat of a curing cement mantle equivalent to 2.5 (Group 1) or 5 mm (Group 2) in vivo in the cemented acetabulum. Matched controls were collected for each patient. Osteocyte counts and viability were assessed by means of haematoxylin and eosin (H&E) stain and lactate dehydrogenase (LDH) assay. Ex vivo experiments were performed to determine the extent of thermal insult. H&E staining proved unreliable for assessing thermal insult in the short term. The LDH assay was reliable and demonstrated a significant reduction in osteocyte viability to a depth of 2.19 mm in group 1 and 9.19 mm in group 2. There was a significant difference between the groups at all depths. The ex vivo experiments revealed thermoclines indicating that host bone in the population undergoing cemented THR is more sensitive to the thermal insult delivered by curing polymethylmethacrylate cement than previously believed. This thermal insult may weaken the fixation between bone and cement and contribute towards aseptic loosening, the commonest cause of failure of THRs.

Lysophosphatidic acid and calcitriol co-operate to promote human osteoblastogenesis: requirement of albumin-bound LPA.

Lysophosphatidic acid (LPA), a pleiotropic signalling lipid is assuming growing significance in osteoblast biology. Although committed osteoblasts from several mammalian species are receptive to LPA far less is known about the potential for LPA to influence osteoblast formation from their mesenchymal progenitors. An essential factor for both bone development and post-natal bone growth and homeostasis is the active metabolite of vitamin D3, calcitriol (D3). Previously we reported how a combination of LPA and D3 synergistically co-operated to enhance the differentiation of immature human osteoblasts. Herein we provide evidence for the formation of human osteoblasts from multiple, primary human bone marrow derived stromal (stem) cells (hBMSCs). Importantly osteoblast development from hBMSCs only occurred when LPA was administered as a complex with albumin, its natural carrier. Collectively our findings support a co-operative role of LPA and D3 in osteoblastogenesis, findings which may aid the development of novel treatment strategies for bone repair.

The effect of growth factor treatment on meniscal chondrocyte proliferation and differentiation on polyglycolic acid scaffolds.

The aim of this investigation was to determine the effect of growth factor treatment on ovine meniscal chondrocyte (OMC) proliferation in vitro and on the production of matrix proteins by OMCs grown within a polyglycolic acid (PGA) scaffold. Analysis of 72-h monolayer cultures using the mean transit time (MTT) assay revealed a greater increase in OMC numbers in the presence of platelet-derived growth factor (PDGF)-AB, PDGF-BB, insulin-like growth factor (IGF)-I, transforming growth factor-beta1 (TGF-beta1) and basic fibroblast growth factor (bFGF) than in untreated controls. In contrast, IGF-II and bone morphogenetic protein-2 had no effect on OMC proliferation at the concentrations tested. The growth factors that elicited the greatest proliferative response (PDGF-AB, PDGF-BB, TGF-beta1, and IGF-I) were subsequently tested for their ability to enhance OMC proliferation and differentiation within PGA scaffolds. Biochemical analysis revealed less glycosaminoglycan (GAG) production in the presence of all growth factors tested compared to untreated control samples. In contrast, all of the growth factors increased collagen type I production by OMCs within the scaffolds at day 20, and all except PDGF-BB resulted in an increase at day 39, when compared to appropriate control samples. With the exception of IGF-I, none of the growth factors tested had any significant effect on collagen type II production. Histological staining of sections from OMC-PGA scaffolds did not reveal any difference in GAG or collagen production between the treatment groups. However, immunohistochemical analysis demonstrated an increase in collagen type I expression and a decrease in collagen type II at day 39 in all growth factortreated constructs, concomitant with a high infiltration of cells. This suggests that PDGF-AB, PDGF-BB, TGF-beta1, and IGF-1 may be useful in future tissue engineering studies for promoting meniscal cell proliferation and differentiation within scaffolds.