Evaluation of a collagen-coated, resorbable fiber scaffold loaded with a peptide basic fibroblast growth factor mimetic in a sheep model of rotator cuff repair.

BACKGROUND: A new scaffold design combined with a peptide growth factor was tested prospectively for safety and for improved tendon healing in sheep. METHODS: The infraspinatus tendon was detached and then surgically repaired to the humerus using sutures and anchors in 50 adult sheep. The repairs in 40 of these sheep were reinforced with a scaffold containing F2A, a peptide mimetic of basic fibroblast growth factor. The sheep were examined after 8 or 26 weeks with magnetic resonance imaging, full necropsy, and histopathologic analysis. A second cohort of 30 sheep underwent surgical repair--20 with scaffolds containing F2A. The 30 shoulders were tested mechanically after 8 weeks. RESULTS: The scaffold and F2A showed no toxicity. Scaffold-repaired tendons were 31% thicker than surgically repaired controls (P = .037) at 8 weeks. There was more new bone formed at the tendon footprint in sheep treated with F2A. Surgically repaired tendons delaminated from the humerus across 14% of the footprint area. The extent of delamination decreased to 1.3% with increasing doses of F2A (P = .004). More of the repair tissue at the footprint was tendon-like in the peptide-treated sheep. On mechanical testing, only 7 shoulders tore at the repair site. The repairs in the other 23 shoulders were already stronger than the midsubstance tendon at 8 weeks. CONCLUSIONS: The new scaffold and peptide safely improved tendon healing.

Hemodynamic characterization of calcified stenotic human aortic valves before and after treatment with a novel aortic valve repair system.

BACKGROUND AND AIM OF THE STUDY: The repair of calcified stenotic aortic valves may be a viable alternative to current valve treatments for early-stage aortic valve disease. To date, evaluation of valve repair feasibility on the benchtop has not been performed. A pulsatile flow system for testing intact human aortic valves was developed to perform quantitative hemodynamic and mechanical assessment of a new aortic valve repair approach. METHODS: Intact calcified human aortic valves were divided into two groups with effective orifice area (EOA) > or =2.0 cm2 (group I, n = 6) or <2.0 cm2 (group II, n = 6). All valves were chemically debrided in stages for up to 60 min. A subset of valves in each group was also surgically debrided. At each stage, pre- and post-treatment hemodynamic assessment and video motion analysis were performed in the pulsatile flow system at multiple levels of physiological loading. Mineral removed was quantified using atomic absorption spectroscopy. RESULTS: Progressive removal of mineral with both mechanical and chemical debridement was associated with improved hemodynamic function of calcified human aortic valves. Improvements in EOA of up to 40% and decreases in transvalvular pressure gradient (deltaP) of up to 46% were seen. No clinically relevant increases in regurgitation were observed. CONCLUSION: Repair of stenotic calcified aortic valves using surgical and chemical debridement showed that removal of calcific deposits was directly associated with improvements in valve hemodynamic function. The level of improvement was proportional to the degree of aortic valve stenosis, to the use of surgical debridement, and to the duration of chemical debridement treatment. The study results suggested that aortic valve repair warrants further investigation as an alternative to current valve treatments in patients with early to mid-stage calcific aortic valve disease.

Dissolution rates of carbonated hydroxyapatite in hydrochloric acid.

Osteoclasts have been shown to dissolve efficiently and effectively the mineral phase of bone by locally controlling the environment surrounding the cell. Although this mineral phase has been identified and well characterized as carbonated hydroxyapatite, there is little understanding of the factors that affect the dissolution properties of this mineral phase. Mimicking the mechanism by which osteoclasts dissolve the mineral phase of bone may provide insight into methods for the decalcification of atherosclerotic mineral deposits in the vascular system. Accordingly, a detailed characterization of the effects of various chemical and mechanical parameters on the dissolution of carbonated hydroxyapatite mineral was investigated in this study. Increases in the mineral dissolution rate (2-10 times) were associated with increases in dissolving solution [H+], osmolality, temperature, and flow rate. Mineral dissolution rate increases (5-8 times) were associated with greater surface area of the mineral and mechanical agitation of the dissolving solution.