Lipo-hydrogel drug carrier for bone regeneration

Hydrogels have widely been studied as drug carriers. However, due to the problems such as: burst drug release, limited drug selection, and low mechanical strength, their application in drug delivery has been greatly reduced. Recently a group of researchers has found a way to break through these restrictions and have demonstrated strong results for a new class of hydrogel drug carriers. [Cheng et al. Applied Materials Today (2018), doi: 10.1016/j.apmt.2018.06.008].

The researchers, from Shanghai Jiao Tong University School of Medicine in China, abandoned conventional methods in constructing drug-loaded hydrogel by directly blending drug or solid drug-loaded carrier recombination with hydrogel. In their study, nonsolid nanocarriers named liposomes were combined with gelatin methacryloyl (GelMA) to fabricate lipo-hydrogel with controlled release of multi-type drugs. Liposomes can carry various kinds of drugs, including water-soluble small molecules, protein drugs, and hydrophobic drugs, and can control their release profile. Gelatin methacryloyl (GelMA) has widespread applications in biomedicine because of its excellent biological properties and tunable physical characteristics.

“The early release of hydrophilic drug (deferoxamine, DFO), mid-term release of bioactive macromolecule (bovine serum albumin, BSA and bone morphogenetic protein 2, BMP-2), and long-term release of liposoluble medicine (paclitaxel, PTX) could be observed in the in vitro drug release results,”  says Wenguo Cui, corresponding author of the study.    

However, to their surprise, these lipo-hydrogels also exhibit preferable mechanical properties in compression, stretching, and periodic cycle in addition to their excellent drug release profiles. The team observed Young’s modulus of lipo-hydrogel has increased two-fold and these composite hydrogels are maintain their structural integrity during the whole cyclic period.

“We discovered that lipo-hydrogel with an appropriate amount of liposomes exhibits superior mechanical performances compared with those without liposomes and those with either too many or too few nanocarriers,” says Ruoyu Cheng, first author of the study.  

The researchers explain that by blending liposome with GelMA and then crosslinking by UV light, that the hydrogel network was formed between GelMA molecules and liposomes was dispersed in the network of the hydrogel. The phosphoric acid group of liposomes generated the micro-cross linking with GelMA molecule by the hydrogen bonding and electrostatic interactions which could further enhance the extent of crosslinking in the lipo-hydrogel. Moreover, when an external force was applied to lipo-hydrogel, the hydrogel decentralized the external force to its micro-crosslinked structure, which reduced the force applied to the hydrogel matrix. The micro-crosslinked structure essentially functioned as a buffer that cushioned the shock brought by the external force.

The composite hydrogel exhibits impressive results including a phase-controlled release, doubled Young’s modulus as compared with GelMA, excellent biocompatibility and functionality. Osteogenesis promotion and angiogenesis differentiation was also observed from the application of these lipo-hydrogels.  

“We thought that the major advantage of hydrogel was the ability to function as a scaffold, but now we think these liposomes modified hydrogel could offer a promising strategy for extending the application of hydrogel in drug delivery and tissue engineering”, says Cheng.