Ikarashi Y, Tsuchiya T, Kaniwa M, Nakamura A
Division of Medical Devices, National Institute of Health Sciences, Tokyo, Japan.
Biol Pharm Bull. 2000 Dec;23(12):1470-6. doi: 10.1248/bpb.23.1470.
This study examined the osteoblast-like MC3T3-E1 cell responses to poly(DL-lactide) (PDLLA) and poly(L-lactide) (PLLA) with different weight average molecular weight (M.W.). Colony formation of MC3T3-E1 cells on the PLLA with M.W. 270000 or 1370000 was slightly lower than that on glass. The protein, DNA and hydroxyproline (HYP) content and alkaline phosphatase (ALP) activity for cells cultured on the PLLA (M.W. 270000 or 1370000) for 14 d were almost similar to those on glass. In contrast, the ALP activity of the cells cultured on low M.W. PLLA (M.W. 20000) increased. Osteoblast differentiation was stimulated by low M.W. PLLA but not by high M.W. PLLA. The addition of low M.W. PDLLA (M.W. 5000 or 10000), L-lactide or L-lactic acid into culture increased the protein, DNA and HYP content and ALP activity for cells at 100 microg/ml. Compared with four chemicals, PDLLA (M.W. 10000) had the strongest simulation effect on the cell. The release of L-lactic acid from PLLA and PDLLA into aqueous solution during incubation only slightly affected cell activity. In a cell-free condition, in the presence of PDLLA, the ALP activity was maintained without inactivation, even after 24 h incubation. Such a phenomenon was not seen with L-lactide and L-lactic acid. This may be a reason why PDLLA has a stronger effect on osteoblast differentiation relative to L-lactic acid. These results suggested that increased osteoblast differentiation was induced by low M.W. PDLLA and PLLA, and these may be used as a effective material in the field of orthopedic and drug delivery systems for the treatment of bone diseases.
本研究检测了成骨样MC3T3-E1细胞对不同重均分子量(M.W.)的聚(DL-丙交酯)(PDLLA)和聚(L-丙交酯)(PLLA)的反应。MC3T3-E1细胞在M.W.为270000或1370000的PLLA上的集落形成略低于在玻璃上的。在M.W.为270000或1370000的PLLA上培养14天的细胞的蛋白质、DNA和羟脯氨酸(HYP)含量以及碱性磷酸酶(ALP)活性与在玻璃上培养的细胞几乎相似。相反,在低M.W.的PLLA(M.W.为20000)上培养的细胞的ALP活性增加。低M.W.的PLLA刺激成骨细胞分化,而高M.W.的PLLA则无此作用。向培养物中添加低M.W.的PDLLA(M.W.为5000或10000)、L-丙交酯或L-乳酸,在100μg/ml时可增加细胞的蛋白质、DNA和HYP含量以及ALP活性。与四种化学物质相比,PDLLA(M.W.为10000)对细胞的刺激作用最强。孵育期间,PLLA和PDLLA中的L-乳酸向水溶液中的释放仅对细胞活性有轻微影响。在无细胞条件下,存在PDLLA时,即使孵育24小时后,ALP活性仍能维持而不被灭活。L-丙交酯和L-乳酸则未观察到这种现象。这可能是PDLLA相对于L-乳酸对成骨细胞分化作用更强的原因。这些结果表明,低M.W.的PDLLA和PLLA可诱导成骨细胞分化增加,它们可能在骨科和药物递送系统领域用作治疗骨疾病的有效材料。