Recombinant Human Perlecan DV and Its LG3 Subdomain Are Neuroprotective and Acutely Functionally Restorative in Severe Experimental Ischemic Stroke.

Despite recent therapeutic advancements, ischemic stroke remains a major cause of death and disability. It has been previously demonstrated that ~ 85-kDa recombinant human perlecan domain V (rhPDV) binds to upregulated integrin receptors (α2ß1 and α5ß1) associated with neuroprotective and functional improvements in various animal models of acute ischemic stroke. Recombinant human perlecan laminin-like globular domain 3 (rhPDVLG3), a 21-kDa C-terminal subdomain of rhPDV, has been demonstrated to more avidly bind to the α2ß1 integrin receptor than its parent molecule and consequently was postulated to evoke significant neuroprotective and functional effects. To test this hypothesis, fifty male C57Bl/6 J mice studied in a t-MCAO model were randomly allocated to either rhPDV treatment, rhPDVLG3, or equivalent volume of PBS at the time of reperfusion in a study where all procedures and analyses were conducted blind to treatment. On post-MCAO day 7, 2,3,5-triphenyltetrazolium chloride staining of brain slices was used to quantify infarct volume. We observed that treatment with rhPDVLG3 reduced infarct volume by 65.6% (p = 0.0001), improved weight loss (p < 0.05), and improved functional outcome measures (p < 0.05) when compared to PBS controls, improvements which were generally greater in magnitude than those observed for 2 mg/kg of rhPDV. In addition, treatment with 6 mg/kg of rhPDVLG3 was observed to significantly reduce mortality due to stroke in one model, an outcome not previously observed for rhPDV. Our initial findings suggest that treatment with rhPDVLG3 provides significant improvement in neuroprotective and functional outcomes in experimental stroke models and that further investigation of rhPDVLG3 as a novel neuroprotective therapy for patients with stroke is warranted.

Within Patient Radiological Comparative Analysis of the Performance of Two Bone Graft Extenders Utilized in Posterolateral Lumbar Fusion: A Retrospective Case Series.

Two bone graft extenders differing in chemical composition were implanted contralaterally in 27 consecutive patients undergoing instrumented posterolateral lumbar fusion as standard-of-care. Bone marrow aspirate and autogenous bone graft were equally combined either with ß-tricalcium phosphate (ß-TCP) or a hybrid biomaterial [containing hyaluronic acid (HyA) but lacking a calcium salt] and implanted between the transverse processes. Fusion status on each side of the vertebrae was retrospectively graded (1-5 scale) on AP planar X-ray at multiple visits as available, through approximately 12 months. Additionally, consolidation or resorption since prior visit for each treatment was recorded. Sides receiving ß-TCP extender showed marked resorption prior to bone consolidation during the first 6 months. By contrast, sides receiving the hybrid biomaterial containing integrated HyA showed rapid bone consolidation by week 6-8, with maintenance of initial bone volume through 12 months. Fusion grade was superior for the hybrid biomaterial, differing significantly from ß-TCP at day 109 and beyond. Fusion success at >12 months was 92.9 vs. 67.9% for the hybrid biomaterial and ß-TCP-treated sides, respectively. The hybrid biomaterial extender demonstrated a shortened time-to-fusion compared to the calcium-based graft. Mode of action has been demonstrated in the literature to differ between these compositions. Therefore, choice of synthetic biomaterial composition may significantly influence the mode of action of cellular events regulating appositional bone growth.

Application of resorbable poly(lactide-co-glycolide) with entangled hyaluronic acid as an autograft extender for posterolateral intertransverse lumbar fusion in rabbits.

Facilitating fusion between bony segments in a reliable and reproducible manner using a synthetic bone graft material has a number of benefits for the surgeon as well as the patient. Although autograft remains the gold standard, associated comorbidities continue to drive the development of new biomaterials for use in spinal fusion. The ability of autograft alone and autograft combined with a radiolucent biomaterial composed of resorbable osteoconductive poly(lactide-co-glycolide) with entangled hyaluronic acid to facilitate fusion was examined in a single-level noninstrumented posterolateral intertransverse lumbar fusion model in New Zealand White rabbits. Progressive bone formation was demonstrated radiographically for the extender group (synthetic biomaterial plus autograft) between 3 and 6 months. Computed tomography revealed a new cortical shell in the fusion mass at 3 and 6 months for both study groups. Tensile testing at 6 months demonstrated that the quality of bone formed between the intertransverse space was equivalent for both study groups. Histologic evaluation of the fusion mass revealed new bone on and adjacent to the transverse processes with the synthetic biomaterial group that extended laterally, supporting the osteoconductive nature of the material. Histological evidence of endochondral bone growth in the intertransverse space was observed for the autograft plus synthetic biomaterial group. Bone remodeling, new marrow spaces, and peripheral cortices were observed for each study group at 3 months that matured by 6 months. These findings support the use of a radiolucent biosynthetic material comprising poly(lactide-co-glycolide) with integrated hyaluronic acid as an autograft extender for lumbar intertransverse fusion.