Engineering a placenta-inspired biomimicking fibrous patch for chondrogenesis through immunomodulation

Area of Science:

• Biomaterials Science
• Immunology
• Regenerative Medicine

Background:

• Post-implantation hyper-inflammation frequently leads to tissue transplant failure and impedes scaffold-based cartilage regeneration.
• Current scaffold modifications have limited success in controlling immune cell infiltration and inflammation.

Purpose of the Study:

• To develop a biomimetic, surface-engineered aligned poly(L-lactic acid) (PLLA) fibrous patch with pH-responsive drug release.
• To shield implanted grafts, modulate post-implantation immune responses, and promote chondrogenesis, inspired by placental functions.

Main Methods:

• Loading hesperetin (Hes), an immunomodulatory biomolecule, onto an aligned fibrous patch using polydopamine (PDA) coating.
• Utilizing PDA's pH-responsive properties for inflammation-triggered Hes release in acidic environments.
• In vitro testing of macrophage phenotypic transition and chondrocyte responses; in vivo subcutaneous implantation in mice and rabbits.

Main Results:

• Successful loading of Hes onto the PDA-PLLA patch with accelerated release in acidic conditions.
• In vitro demonstration of macrophage polarization from pro-inflammatory to anti-inflammatory states and positive effects on chondrocytes.
• In vivo validation of reduced immune rejection, inhibited fibrous encapsulation, and enhanced cartilage remodeling in implanted grafts.

Conclusions:

• The Hes@PDA-PLLA biomimetic patch acts as an immune-responsive protective barrier, mitigating host immune rejection of implants.
• This engineered system offers a novel strategy to improve the transplantation success of allogeneic cartilage and other cell-based implants.