Surface-modified injectable poly(ethylene-glycol) diacrylate-based cryogels for localized gene delivery

Area of Science:

• Biomaterials Science
• Gene Therapy
• Immunotherapy

Background:

• Lentiviral transduction is crucial for gene therapy and CAR-T cell immunotherapy but often requires ex vivo modification and systemic cell administration.
• Current methods face challenges with off-target effects and efficiency, necessitating novel delivery systems.

Purpose of the Study:

• To develop and evaluate injectable poly(ethylene glycol) diacrylate (PEGDA)-based scaffolds for in situ lentivirus-mediated gene delivery.
• To assess the feasibility of using these scaffolds for localized and efficient lentiviral transduction.

Main Methods:

• PEGDA scaffolds were fabricated using cryogelation and modified with poly(L-lysine) (PLL) for lentivirus immobilization.
• Scaffolds were tested for injectability, shape recovery, cell infiltration, and hemocompatibility in vitro and in vivo.
• Histology and immunophenotyping were used to evaluate inflammatory response and cell viability.

Main Results:

• Injectable PEGDA scaffolds demonstrated excellent flow through surgical needles and rapid shape recovery.
• PLL modification effectively immobilized lentivirus, and the porous structure facilitated cell infiltration and interaction.
• In vitro and in vivo studies confirmed scaffold hemocompatibility, cell viability, and minimal inflammatory response.

Conclusions:

• Preformed injectable PEGDA scaffolds offer a novel, non-invasive, and localized approach for in situ lentiviral transduction.
• This technology holds significant potential for advancing tissue engineering and immunotherapeutic applications.