Biosynthesizing lignin dehydrogenation polymer to fabricate hybrid hydrogel composite with hyaluronic acid for cartilage repair

Lignin possesses a number of functional groups including phenolic hydroxyl and methoxy groups, which grant its bioactivity for the fabrication of bio-polymer-based composites in bone tissue engineering applications. However, the heterogeneity of natural lignin limits its use in biomedicine. In the present study, a bio-enzyme approach was proposed to synthesize lignin-dehydrogenated polymers from the precursors of arabinogalactan (DHP-A) and xylose (DHP-X), which possess more homogeneous substructures with appropriate functional groups. Both DHP-A and DHP-X showed excellent in vitro abilities for regulating biocompatibility, "pre-oxidation," and chondrogenic differentiation, in which DHP-A possessed cartilage repair ability due to its abundant content of phenolic hydroxyl groups (3.00 mmol g−1). Hence, DHP-A was hybridized with hyaluronic acid (HA) to prepare a hydrogel (DHP-HA) composite, which exhibited the compressive strength and modulus of 810 kPa and 310 kPa, respectively. Notably, these properties closely resemble those of articular cartilage, which typically ranges from 320 to 810 kPa. The application of DHP-HA hydrogel composite in a rat cartilage defect model in vivo revealed that it promoted the regeneration of hyaline cartilage rather than hypertrophic cartilage, which could heal 66.22–79.26% of the cartilage defects compared to the control group. Pre-oxidation of DHP-A elicits a mechanism that activates the oxidative stress system, leading to an augmented stress response and consequent increase in stress resistance. This study introduces a pioneering enzymatic synthesis technique to prepare the biologically active lignin for creating bio-polymer-based composites, demonstrating its potential as an innovative avenue for therapeutic cartilage regeneration. Bioenzymatically synthesized lignin dehydrogenation polymers to hybridize with hyaluronic acid to prepare hydrogel composites for promoting cartilage defect repair.