Abdel-Sayed Philippe, Kaeppeli Ariane, Siriwardena Thissa, Darbre Tamis, Perron Karl, Jafari Paris, Reymond Jean-Louis, Pioletti Dominique P, Applegate Lee Ann
Laboratory of Biomechanical Orthopedics, Institute of Bioengineering, École Polytechnique Fédérale de Lausanne (EPFL), Switzerland.
Department of Chemistry and Biochemistry University of Bern, Switzerland.
Sci Rep. 2016 Feb 25;6:22020. doi: 10.1038/srep22020.
Multi-drug resistant Pseudomonas aeruginosa has increased progressively and impedes further regression in mortality in burn patients. Such wound infections serve as bacterial reservoir for nosocomial infections and are associated with significant morbidity and costs. Anti-microbial polycationic dendrimers G3KL and G3RL, able to kill multi-drug resistant P. aeruginosa, have been previously developed. The combination of these dendrimers with a class of biological bandages made of progenitor skin cells, which secrete growth factors, could positively impact wound-healing processes. However, polycations are known to be used as anti-angiogenic agents for tumor suppression. Since, neovascularization is pivotal in the healing of deep burn-wounds, the use of anti-microbial dendrimers may thus hinder the healing processes. Surprisingly, we have seen in this study that G3KL and G3RL dendrimers can have angiogenic effects. Moreover, we have shown that a dendrimer concentration ranging between 50 and 100 μg/mL in combination with the biological bandages can suppress bacterial growth without altering cell viability up to 5 days. These results show that antimicrobial dendrimers can be used in combination with biological bandages and could potentially improve the healing process with an enhanced angiogenesis.
多重耐药铜绿假单胞菌逐渐增多,阻碍了烧伤患者死亡率的进一步下降。此类伤口感染成为医院感染的细菌储存库,并与显著的发病率和成本相关。先前已开发出能够杀死多重耐药铜绿假单胞菌的抗菌聚阳离子树枝状大分子G3KL和G3RL。这些树枝状大分子与一类由能分泌生长因子的祖代皮肤细胞制成的生物绷带相结合,可能对伤口愈合过程产生积极影响。然而,已知聚阳离子被用作抑制肿瘤的抗血管生成剂。由于新血管形成在深度烧伤伤口愈合中至关重要,因此使用抗菌树枝状大分子可能会阻碍愈合过程。令人惊讶的是,我们在本研究中发现G3KL和G3RL树枝状大分子具有血管生成作用。此外,我们已经表明,浓度在50至100μg/mL之间的树枝状大分子与生物绷带联合使用时,可抑制细菌生长,且在长达5天的时间内不改变细胞活力。这些结果表明,抗菌树枝状大分子可与生物绷带联合使用,并可能通过增强血管生成来潜在地改善愈合过程。