Multidisciplinary Research Center, Shantou University, Shantou 515063, Guangdong, China.
Biomaterials. 2011 Apr;32(10):2546-55. doi: 10.1016/j.biomaterials.2010.12.051. Epub 2011 Jan 19.
Polyhydroxyalkanoates (PHA) are aliphatic polyesters synthesized by many bacteria. Because of their flexible mechanical strengths, superior elastic property, biodegradability and biocompatibility, PHA have been developed for applications as medical implants, drug delivery matrices, and devices to support cell growth. Lots of studies showed that PHA matrices improved cell proliferation and tissue regeneration. However, the possibility of whether rapid cell proliferation on PHA matrices will induce tumor formation is unclear. Here we confirmed that proliferating rat osteoblasts grown on films of various PHA including PHB, PHBV, P3HB4HB, PHBHHx and PHBVHHx did not lead to cancer induction at least for p8th. Cell proliferation was evaluated by the incorporation of 5-bromodeoxyuridine (BrdU), the transcript expression of cancer related genes Ki67, p53 and c-Fos was monitored by quantitative Real-time PCR, the results showed the cells proliferating on the PHA films were under normal cell cycle regulation. Moreover, DNA aneuploid and telomerase activity were only detected in the positive control UMR-108 cells; compared with cells grown on films, UMR-108 cells had longer telomeres, further demonstrated the normal status of cells proliferating on the PHA films. It indicated that the above PHA family members could be used to support cell growth without indication of susceptibility to tumor induction. These results will be important for promoting the application of PHA as new members of biomaterials.
聚羟基脂肪酸酯（PHA）是许多细菌合成的脂肪族聚酯。由于其具有灵活的机械强度、卓越的弹性、生物降解性和生物相容性，PHA 已被开发用于医疗植入物、药物输送基质和支持细胞生长的设备。大量研究表明，PHA 基质可促进细胞增殖和组织再生。然而，在 PHA 基质上快速增殖的细胞是否会导致肿瘤形成尚不清楚。在这里，我们证实，在包括 PHB、PHBV、P3HB4HB、PHBHHx 和 PHBVHHx 在内的各种 PHA 薄膜上生长的增殖大鼠成骨细胞，至少在第 8 天不会导致癌症形成。通过掺入 5-溴脱氧尿苷（BrdU）来评估细胞增殖，通过定量实时 PCR 监测与癌症相关的基因 Ki67、p53 和 c-Fos 的转录表达，结果表明，在 PHA 薄膜上增殖的细胞受到正常细胞周期调控。此外，仅在阳性对照 UMR-108 细胞中检测到 DNA 非整倍体和端粒酶活性；与在薄膜上生长的细胞相比，UMR-108 细胞具有更长的端粒，进一步证明了在 PHA 薄膜上增殖的细胞处于正常状态。这表明上述 PHA 家族成员可用于支持细胞生长，而不会引起肿瘤诱导的易感性。这些结果对于促进 PHA 作为生物材料的新成员的应用将是重要的。
