Effect of Hypoxia Preconditioned Secretomes on Lymphangiogenic and Angiogenic Sprouting: An in Vitro Analysis

Hypoxia Preconditioned Plasma (HPP) and Serum (HPS) are two blood-derived autologous growth factor compositions that are being clinically employed as tools for promoting tissue regeneration, and have been extensively examined for their angiogenic activity. As yet, their ability to stimulate/support lymphangiogenesis remains unknown, although this is an important but often-neglected process in wound healing and tissue repair. Here we set out to characterize the potential of hypoxia preconditioned secretomes as promoters of angiogenic and lymphangiogenic sprouting in vitro. We first analysed HPP/HPS in terms of pro- (VEGF-C) and anti- (TSP-1, PF-4) angiogenic/lymphangiogenic growth factor concentration, before testing their ability to stimulate microvessel sprouting in the mouse aortic ring assay and lymphatic sprouting in the thoracic duct ring assay. The origin of lymphatic structures was validated with lymph-specific immunohistochemical staining (Anti-LYVE-1) and lymphatic vessel-associated protein (polydom) quantification in culture supernatants. HPP/HPS induced greater angiogenic and lymphatic sprouting compared to non-hypoxia preconditioned samples (normal plasma/serum), a response that was compatible with their higher VEGF-C concentration. These findings demonstrate that hypoxia preconditioned blood-derived secretomes have the ability to not only support sprouting angiogenesis, but also lymphangiogenesis, which underlines their multimodal regenerative potential.

Osteoinductive bone graft substitutes for lumbar fusion: a systematic review

Object Autograft and allograft, the standard approaches for lumbar fusion procedures, have important disadvantages. Bone graft substitutes such as recombinant human bone morphogenetic proteins (rhBMP-2 and rhBMP-7) have emerged as viable alternatives. The authors conducted a systematic review to compare the efficacy and safety of osteoinductive bone graft substitutes using autografts and allografts in lumbar fusion. Methods A search for prospective controlled trials was conducted on MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials databases. Data were extracted for key outcomes including radiographically demonstrated nonunion, Oswestry Disability Index, operating time, blood loss, and length of hospital stay. The quality of randomized controlled trials was assessed using the Jadad scale. Meta-analyses were performed when feasible, and heterogeneity was assessed using the Q statistic and the I2 statistic. Results Seventeen of 732 potential studies met the inclusion criteria, with 9 examining rhBMP-2, 3 examining rhBMP-7, 3 examining demineralized bone matrix, and 2 examining autologous growth factor. Recombinant human BMP-2 significantly decreased radiographic nonunion when compared with autologous iliac crest bone graft (AIBG) in a meta-analysis (relative risk 0.27, 95% CI 0.16–0.46). Stratification of meta-analyses by the type of surgical procedure performed yielded similar results. Funnel plots suggested publication bias. Trials of rhBMP-2 suggested reductions in the operating time and surgical blood loss, with less effect on the length of hospital stay. There was no difference in radiographic nonunion with the use of rhBMP-7 when compared with AIBG (relative risk 1.02, 95% CI 0.52–1.98). Neither rhBMP-2 nor rhBMP-7 demonstrated a significant improvement on the Oswestry Disability Index when compared with AIBG. The limited data on demineralized bone matrix and autologous growth factor showed no significant improvement in radiographic outcomes. Conclusions Recombinant human BMP-2 may be an effective alternative to AIBG in lumbar fusion. Data are limited for other bone graft substitutes.