Dynamic adaptive coassembled sericin protein orchestrating stem cell development for nucleus pulposus regeneration

Area of Science:

• Biomaterials Science
• Tissue Engineering
• Stem Cell Biology

Background:

• The natural extracellular matrix (ECM) provides a dynamic microenvironment crucial for stem cell development.
• Intervertebral disc (IVD) degeneration involves complex mechanical and biochemical signaling pathways.
• Current regenerative strategies require advanced biomaterials that mimic native ECM properties.

Purpose of the Study:

• To engineer a dynamic adaptive protein gel that replicates the nucleus pulposus (NP)-like viscoelasticity.
• To investigate the gel's ability to orchestrate stem cell development through mechanotransduction.
• To evaluate the potential of the engineered gel for intervertebral disc regeneration in vivo.

Main Methods:

• Coassembling bioactive sericin with an amphiphilic tripeptide to form a viscoelastic protein gel.
• Assessing the gel's ability to activate integrin β3-mediated mechanotransduction and promote cytoskeletal remodeling.
• Evaluating stem cell differentiation and ECM synthesis in response to the gel and kartogenin treatment.
• In vivo studies to assess NP tissue integrity and regenerative potential.

Main Results:

• The engineered protein gel exhibited rapid stress relaxation and NP-like viscoelasticity.
• The gel successfully activated integrin β3 signaling, promoted cytoskeletal remodeling, and facilitated YAP nuclear translocation.
• Stem cell development was orchestrated, leading to increased bioactive factors and ECM synthesis.
• Incorporation of kartogenin enhanced stem cell differentiation and preserved NP tissue integrity in vivo.

Conclusions:

• A phase separation-driven, adaptive protein matrix was successfully established.
• The engineered matrix effectively orchestrates both mechanical and biochemical signaling for stem cell development.
• This novel biomaterial shows significant potential for robust intervertebral disc regeneration.