Application of adipose tissue-derived stem cells in a rat rotator cuff repair model.

INTRODUCTION: Healing tissue of the rotator cuff does not regenerate the native enthesis; fibrovascular scar tissue is formed instead and this has less favourable biomechanical properties. The purpose of this study was to determine if the application of adipose tissue-derived stem cells (ASCs) could improve biomechanical and histological properties of the repair. MATERIAL AND METHODS: Fifty Sprague-Dawley rats underwent detachment and repair of the supraspinatus tendon, 32 for the biomechanical study and 18 for the histological examination. Animals were randomised in two groups to receive either a collagen carrier alone (untreated group) or the carrier plus 2×10(6) ASCs (ASCs group). A control group (suture only) was also included for the histological examination. The animals were sacrificed at 2 and 4 weeks for the biomechanical study and at 24 hours, and 1 and 4 weeks for the histological study. Maximum load failure energy, elastic energy, mechanical deformation, stiffness and absorbed energy were measured. Immunofluorescence testing was conducted to show the presence of ASCs in the repair area. RESULTS: There were no differences between the untreated group and the ASCs group in any of the biomechanical variables at the 2- and 4-week time points. The mechanical deformation before failure was higher for the ASCs group compared with the untreated group at 2 weeks and 4 weeks (p=0.09), as was the absorbed energy (p=0.06). Differences in maximum load to failure between 2 and 4 weeks were significant for the untreated group (p=0.04) but not for the ASCs group (p=0.17). Histological examination showed less acute inflammation with diminished presence of oedema and neutrophils in the ASCs group. There were no differences in the orientation of collagen fibres between groups at either time point. In the ASCs group, collagen was present only at the last time point. CONCLUSION: The application of ASCs in a rat rotator cuff repair model did not improve the biomechanical properties of the tendon-to-bone healing. However, the ASCs group showed less inflammation, which may lead to a more elastic repair and less scarred healing.

Proximal humerus fracture rotational stability after fixation using a locking plate or a fixed-angle locked nail: the role of implant stiffness.

BACKGROUND: Fixed-angle locked devices have been developed to improve internal fixation of proximal humerus fractures. Available low-profile precontoured locking plates and intramedullary nails with fixed-angle interlocks are currently favored by most surgeons in this setting. The aim of this study was to assess the relative stability of these two methods of fixation under torsion load. METHODS: A surgical neck osteotomy was created in six pairs of embalmed humeri. In each pair, one specimen was secured with a titanium locking-compression plate, and the contralateral was secured with a titanium nail with a proximal locked spiral blade. The specimens were first tested cyclically in internal-external rotation for 10,000 cycles to evaluate interfragmentary motion (dynamic study). At the end of the cyclic testing, the specimens were loaded to failure in external rotation to measure torque to failure and construct stiffness (static study). FINDINGS: There were no significant differences in interfragmentary motion between the two fixation devices in the dynamic study. When tested to failure, fixation with the locking plate tolerated on average 20 more degrees in torsion before failure, and demonstrated higher torsional load to failure and less torsional stiffness (P<0.05). INTERPRETATION: Both locking plates and locked intramedullary nails may provide enough stability to avoid secondary displacement of proximal humerus fractures during early physical therapy. Locking plates demonstrated superior biomechanical properties under high rotational loads than locked intramedullary nails in a cadaveric proximal humerus two-part osteotomy model, and could provide more protection against unexpected high torsion loads.

Comparative effects of bicalutamide (Casodex) versus orchidectomy on bone mineral density, bone remodelling, and bone biomechanics in healthy rats.

INTRODUCTION: The aim of this work was to analyze the effects produced on bone mineral density (BMD) by the administration of bicalutamide and to compare them with those produced by orchidectomy. Bone formation rate (serum osteocalcin), bone resorption (serum carboxyterminal telopeptide of collagen I; CTX), and biomechanical properties of bone were also studied. METHODS: Thirty-eight male Wistar rats were used: (1) Sham group, rats sham operated at 16 weeks of age; (2) OQX group, rats orchidectomized at 16 weeks of age, and (3) Bic group, rats sham operated at 16 weeks of age and treated during 6 weeks with bicalutamide. The rats were sacrificed at 22 weeks of age, and the BMD in femur and lumbar spine was determined. Serum osteocalcin and serum CTX were also analyzed. Biomechanical parameters related to torsion assay were also studied. RESULTS: The OQX group showed a significant decrease in femoral BMD with respect to Sham rats, whereas bicalutamide treatment did not produce any significant change in BMD. Both Sham and Bic groups showed similar serum osteocalcin and CTX values, whereas OQX rats presented higher osteocalcin and CTX levels than the Sham group. The OQX group showed a significant decrease in femoral thickness. No significant differences were observed in the rest of the biomechanical parameters between groups. CONCLUSION: These results indicate that bicalutamide treatment, in spite of its anti-androgenic properties, does not affect bone remodelling nor BMD in male healthy rats, suggesting that this compound may function as a selective androgen receptor modulator for effects on bone remodelling in the osteoblasts.

Interleukin-18 binding protein reduces b16 melanoma hepatic metastasis by neutralizing adhesiveness and growth factors of sinusoidal endothelium.

We studied the role of endogenous interleukin (IL)-18 in hepatic metastasis by blocking this cytokine using the naturally occurring IL-18 binding protein (IL-18BP). A single i.p. dose of IL-18BP given 30 min before intrasplenic injection of murine B16 melanoma (B16M) cells reduced the number of hepatic metastatic foci by 75% and metastatic volume by 80%. Same treatment reduced the intrahepatic retention of luciferase-transfected B16M by 50% and abolished VCAM-1 up-regulation in the hepatic microvasculature, as assessed by reverse transcription-PCR, Western blot, and immunohistochemistry. Twelve hours after IL-18BP, hepatic sinusoidal endothelium (HSE) cells were isolated, and adhesion of B16M cells to these cultured HSE cells was reduced to the level of vehicle-treated mice. IL-18BP treatment of mice with established micrometastases resulted in a 25% decrease in metastasis number and 40% decrease in metastasis volume, suggesting inhibition of endogenous growth factors. Indeed, the addition of IL-18BP to normal HSE abolished the release of melanoma cell growth factor(s) induced by B16M. IL-18 promoted the in vitro growth of B16M and human melanoma cells, which was IL-1 dependent. These data demonstrate a significant role of endogenous IL-18 on hepatic metastasis by up-regulating melanoma cell adhesion to HSE cells and tumor growth, implicating a possible antimetastatic benefit of neutralizing IL-18.