Silk-hydrogel functionalized with human decellularized Wharton's jelly extracellular matrix as a minimally invasive injectable hydrogel system for potential nucleus pulposus tissue replacement therapy

Intervertebral disc degeneration is a primary cause for chronic low back pain, a common health problem with high incidence and the leading cause of disability globally. The early stages of disc degeneration in terms of functional and anatomical abnormalities start from the central nucleus pulposus tissue of the intervertebral disc; hence its regeneration has become a prime concern. A plethora of hydrogel systems have been investigated as nucleus pulposus tissue substitute over the years, with limited clinical translation. In the present study, we formulated a minimally invasive injectable cross-linker-free bioactive silk-based hybrid hydrogel system functionalized with decellularized human Wharton's jelly extracellular matrix as an ampule of bioactive cues. The centrifugation based decellularization method removed >92 % of cellular components and preserved >83 % of extracellular matrix composition. The hydrogels were investigated for secondary structure and surface properties through infrared spectroscopy and electron micrographs, respectively. Notably, the developed hydrogels were found to mimic the rheological and mechanical properties of native nucleus pulposus tissue when decellularized Wharton's jelly extracellular matrix content was 0.5 % (w/v) in the base silk hydrogel. Finally, the hydrogels were found to support cell viability, proliferation, and tissue maturation offering great potential for future applications related to nucleus pulposus tissue engineering.