Silk nanoengineering for in situ forming injectable ECM-inspired hydrogels

Area of Science:

• Biomaterials Science
• Tissue Engineering
• Regenerative Medicine

Background:

• Injectable hydrogels are crucial for tissue regeneration but face challenges in mimicking the extracellular matrix (ECM) and balancing mechanical properties with injectability.
• Hyaluronic acid (HA) is promising for therapeutics but lacks an ECM-like structure and optimal mechanical characteristics for injectable applications.

Purpose of the Study:

• To develop an in situ forming, injectable hydrogel that mimics the native ECM by combining structural proteins and glycosaminoglycans.
• To overcome the trade-off between mechanical properties and injectability in current hydrogel systems.
• To create a cell-instructive biomaterial for enhanced stem cell survival and tissue integration.

Main Methods:

• Combined nanofibrillated silks (nanosilks) with RGD peptide and tyramine-modified hyaluronic acid (HA-Tyr) to create a composite hydrogel precursor.
• Utilized covalent interfacial crosslinking to enhance the hydrogel's structural integrity and resistance to degradation.
• Evaluated injectability, in situ gelation, mechanical properties, biocompatibility, and stem cell response in vitro and in vivo.

Main Results:

• The HA-Tyr/nanosilks precursor solution demonstrated excellent injectability (extrusion force < 2 N) and rapid in situ gelation.
• The hydrogel exhibited enhanced mechanical strength, elastic recovery, and enzymatic resistance due to the nanosilk network.
• Encapsulated stem cells showed improved proliferation and long-term survival within the hydrogel, with successful host tissue integration upon subcutaneous implantation.

Conclusions:

• The developed injectable hydrogel effectively mimics the ECM, providing a bioactive and cell-instructive microenvironment.
• This silk nanoengineering strategy resolves the conventional trade-offs in injectable hydrogels, offering a promising platform for minimally invasive regenerative therapies.
• The material supports cell viability and promotes host tissue integration, expanding the potential of stem cell-based treatments for soft tissue repair.