Injectable hydrogels offer great potential to augment
damaged or
degenerated soft tissues. A key criterion for such gels is that their
modulus is as close as possible to that of the target tissue. The
majority of synthetic hydrogels have used low molecular weight polymer
chains which may cause problems if they diffuse away from the injection
site and/or increase the local osmotic pressure. We previously introduced
a different approach of injecting preformed ultra-high molecular weight
pH-responsive microgels (MGs) that interlink to form hydrogels. MGs
are crosslinked polymer colloid particles that swell when the pH approaches
the particle pKa. These colloidal hydrogels
are termed doubly crosslinked microgels (DX MGs). The gel moduli of
previous DX MGs were much greater than that reported for human nucleus
pulposus (NP) tissue of the spinal intervertebral disk. Here, we replace
some of the pH-responsive poly(ethyl acrylate-co-methacrylic
acid) (PEA-MAA) MGs with hydrophilic non-ionic MGs based on poly(N-vinylformamide) (NVF). We investigate the morphology and
mechanical properties of these new injectable composite DX MGs and
show that the mechanical properties can be tuned by systematically
varying the NVF MG content. Using this approach, the gel moduli close
to that for NP tissue are achieved. These injectable new pH-responsive
gels exhibit low cytotoxicity. Our work provides a potential new system
for minimally invasive intervertebral disk augmentation.