A single injection of protein-loaded coacervate-gel significantly improves cardiac function post infarction.

After myocardial infarction (MI), the heart undergoes fibrotic pathological remodeling instead of repair and regeneration. With multiple pathologies developing after MI, treatment using several proteins is expected to address this range of pathologies more effectively than a single-agent therapy. A factorial design of experiments study guided us to combine three complementary factors in one injection: tissue inhibitor of metalloproteinases-3 (TIMP-3) was embedded in a fibrin gel for signaling in the initial phase of the treatment, while basic fibroblast growth factor (FGF-2) and stromal cell-derived factor 1-alpha (SDF-1α) were embedded in heparin-based coacervates for sustained release and distributed within the same fibrin gel to exert their effects over a longer period. The gel was then tested in a rat model of myocardial infarction. Contractility of rat hearts treated with the protein coacervate-gel composite stabilized and slightly improved after the first week while contractility continued to decrease in rats treated with free proteins or saline over the 8 week study period. Hearts receiving the protein coacervate-gel composite treatment also exhibited reduced ventricular dilation, inflammation, fibrosis, and extracellular matrix (ECM) degradation. Revascularization, cardiomyocyte preservation, stem cell homing, and increased myocardial strain likely all contributed to the repair. This study demonstrates the potential of a multifactorial therapeutic approach in MI, using three complementary proteins delivered sequentially for comprehensive healing. The study also shows the necessity of controlled delivery for growth factors and cytokines to be an effective treatment.

Vertebroplasty increases trabecular microfractures in elderly female cadaver spines.

UNLABELLED: This study assessed whether vertebroplasty increases trabecular bone microfractures in adjacent vertebrae of elderly female cadavers. Results indicated microfractures were almost two times greater in superior adjacent vertebrae for vertebroplasty treated spines compared to non-treated controls. This finding may aid in developing improved treatments for osteoporotic women with vertebral fractures. INTRODUCTION: Although vertebroplasty may stabilize compression fractures and reduce pain, subsequent vertebral fractures occur in approximately 25 % of patients, reducing the overall safety of this procedure. This is particularly a concern in vertebrae surrounding the treated level where bone cement may cause abnormal transfer of forces to adjacent spinal structures. Therefore, the objective of this study was to quantify the effects of vertebroplasty on local trabecular bone damage in adjacent vertebrae. METHODS: Five level motion segments (T11-L3) from osteopenic/osteoporotic female cadaver spines (T-score -2.9 ± 1.0) were assigned into either vertebroplasty or control (no vertebroplasty) groups (n = 10/group) such that T-score, trabecular microarchitecture, and age were similar between groups. Compression fractures were created in the L 1 vertebra of all specimens and PMMA bone cement was injected into the fractured vertebra of vertebroplasty specimens. All spine segments were subjected to cyclic axial compression (685-1370 N) for 115,000 cycles. Post-testing, trabecular cubes were cut from adjacent (T12 and L2) vertebral bodies and histologically processed. Trabecular microfractures were identified and normalized by bone area in each section. RESULTS: There were significantly more trabecular microfractures (p < 0.001) in superior adjacent vertebral bodies of the vertebroplasty group (0.091 ± 0.025 microfractures/mm(2)) when compared to the control group (0.049 ± 0.018 microfractures/mm(2)). However, there was no difference in trabecular microfractures (p = 0.835) between vertebroplasty (0.045 ± 0.022 microfractures/mm(2)) and control groups (0.035 ± 0.013 microfractures/mm(2)) for inferior adjacent vertebral bodies. CONCLUSIONS: Vertebroplasty specifically impacts the superior adjacent vertebrae of elderly female spines resulting in almost two times more trabecular microfractures when compared to non-treated controls.