Introduction: Weak hydrophilicity and poor cell affinity of poly(d,l-lactic acid) (PDLLA) are major drawbacks that restrict its wide applications in medical areas. This article focuses on organic/inorganic composite scaffolds for tissue regeneration. RGD (Arg-Gly-Asp) peptide is an amino acid sequence for tissue cells recognize and grafted with PDLLA matrix. Nano hydroxyapatite (n-HAP) is induced into degradable PDLLA/RGD composite to neutralize the acidity. Finally porous composite material with hydroxyapatite (HA) was prepared. Scaffold with high porosity and high interconnectivity is beneficial tissue regeneration.
Materials and Methods: The poly{(lactic acid)-co-[(maleic anhydride)-alt-(hexanediamine)]}(BMPLA) was synthesized and modified with RGD peptide. The structures of PRGD and its precursors were characterized by FT-IR, 1H NMR, 13C NMR, UV, SEM, Amino acid analysis (AAA). Firstly, Maleic anhydride (MAH) was grafted onto the backbone of PDLLA by melt free radical copolymerization using BPO as initiator. The reaction process was exactly controlled by temperature and treating time. Secondly, Hexanediamine was grafted onto the backbone of PDLLA at low temperatures. The reaction lasted for 10 min below 8°C and 30 min at 28°C. The final product was HMPLA. The main factors affecting the produce rate of HMPLA was investigated . Thirdly, the polymer matrix was modified with RGD peptide at low temperatures. The pH of the mixture was adjusted to 7-8 with tri-ethylamine. The amino acid concentrations determined by AAA. The material hydrophilicity was tested by the material hydrophilicity. Finally, Nano hydroxyapatite (n-HAP) is induced into degradable PDLLA/RGD composite to prepared the porous composite materials used sodium chloride as porogen.
Results and Discussion: PRGD/PDLLA/n-HAP scaffolds were obtained by the above method. HAP particles homogeneously dispersed in matrix are 60-80nm in diameter. The pore size of composited is about 200μm. The concentration, temperature and reaction time were the main factors affecting the produce rate of HMPLA. The results show that the best experimental program is temperature 8 °C, time 1 h and the amount of material hexanediamine excess by 80%. Table 1 shows RGD peptide content grafted on PRGD. The amino acid contents ranges from 16.5μmol/g to 48.8 μmol/g. The hydrophilicity on PRGD is significantly higher than that the pure PDLLA. Table 1 Amino acid analysis PRGD Glycine (μmol/g) Arginine (μmol/g) Aspartic acid (μmol/g) Tyrosine (μmol/g) 48.8 21.5 28.7 16.5 .
Conclusions: 1.The maleic anhydride, hexanediamine and GRGDY were successfully grafted onto polylactic acid side chain. The hydrophilicity on PRGD is significantly higher than that the pure PDLLA. 2. The amount of hexanediamine should not be too much, because the polylactic acid will accelerate the degradation and molecular weight reduction under alkaline condition. 3. The pore size of composited is about 200μm when sodium chloride was used as porogen.
Natural Science Foundation of China (Project No. 51172172); Key Scientific and Technological Project of Wuhan City (Project No. 201160923310)
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