Existing chemical crosslinking methods such as UV-based, genipin or enzymatic are often cytotoxic and incompatible with the presence of living cells, or result in inhomogeneous reinforcement (primarily surface over core).
Moreover, reinforcing ECM whilst ensuring uniform cell viability and spatial distribution in thick tissues remains challenging, particularly when robust mechanical properties are needed post-fabrication.

Technology Description
• A reinforcement process for engineered cell-laden ECM scaffolds post using small-molecule crosslinking
• The reinforcing molecule, such as oxidized polyaldehyde saccharide, diffuses throughout the construct, forming covalent bonds (via Schiff base click chemistry) with amine groups in ECM proteins, thereby chemically crosslinking the matrix homogeneously
• The method is cell-friendly (physiological) conditions, preserving viability and function of resident cells
• A broad platform applicable to a range of tissue types, bioinks, and fabrication methods

Potential Applications
• Cardiac Repair: 3D-bioprinted cardiac patches for treatment of myocardial infarction or other heart conditions requiring tissue implantation
• Regenerative Medicine: Reinforced tissue grafts for organs or structures subjected to mechanical stress such as muscle, vessel, bladder and intestinal tissue
• Transplantation: dramatic improvement in compressive modulus (≥10% increase) allows for handling, suturing, compression, and injection without structure loss or cell damage during minimally invasive surgical procedures
• In Vitro Tissue Models: more robust complex tissue models for disease modeling or drug screening

Value Proposition Summary
The technology enables the fabrication of living, thick, vascularized, mechanically robust tissue constructs by post-assembly chemical reinforcement with a biocompatible, cell-friendly small-molecule crosslinker, overcoming longstanding limitations in tissue engineering and ECM-based materials.

Stage
• US provisional patent
• in vitro POC in reinforced engineered 3D printed cardiac tissues, from fabrication through to injection to simulate a minimally invasive procedure

References
Silberman et al 2023, Advanced Materials