Neuro-Immunomodulatory Potential of Nanoenabled 4D Bioprinted Microtissue for Cartilage Tissue Engineering

Area of Science:

• Biomaterials Science
• Tissue Engineering
• Nanotechnology

Background:

• Cartilage defects cause inflammation and degradation, driving osteoarthritis (OA) progression.
• Current OA treatments lack anti-inflammatory effects and fail to address underlying disease mechanisms.
• Chondrocyte catabolism and extracellular matrix (ECM) breakdown are key pathological features of OA.

Purpose of the Study:

• To develop a nano-enabled human cartilage microtissue (HCM) for localized inflammation mitigation and chondroprotection in OA.
• To investigate the anti-inflammatory and chondroprotective effects of ibuprofen-loaded poly(lactic-co-glycolic acid) nanoparticles (ibu-PLGA NPs) within a 4D-bioprinted HCM.
• To evaluate the in vivo immunogenicity and effects on nerve sprouting of the nano-enabled HCM.

Main Methods:

• 4D-bioprinting of HCM nano-enabled with ibu-PLGA NPs.
• In vitro assessment of chondrocyte response to inflammation (IL-1β, IL-6 release, ECM production).
• In vivo evaluation using an air pouch mouse model to assess immunogenicity, inflammatory mediator secretion, and innervation.

Main Results:

• Nano-enabled HCM reduced inflammatory cytokine release (IL-1β, IL-6) and sustained ECM production in vitro.
• In vivo studies showed nano-enabled HCM secretomes were non-immunogenic and reduced local inflammatory cell recruitment and mediator secretion.
• The nano-enabled HCM secretome did not impact local skin innervation, suggesting it impedes nerve growth.

Conclusions:

• Nano-enabled HCM with ibu-PLGA NPs is a promising strategy for mitigating inflammation and protecting cartilage ECM in OA.
• This approach offers localized therapeutic delivery, addressing key OA pathological pathways.
• The technology presents an innovative direction in cartilage tissue engineering for treating inflammatory joint diseases.