Biomaterials scienceApr 27, 2026

How mitochondrial cleanup by PINK1/Parkin influences immune cell behavior and titanium implant integration during inflammation

Longevity & Aging Weekly Brief ↗PubMed ↗DOI ↗

Abstract

PINK1/Parkin-dependent mitophagy is essential for M2 macrophage polarization at titanium implant interfaces.

Micro-/nanostructured titanium surfaces, such as sandblasted/acid-etched and anodized, promote M2 macrophage polarization.
The upregulation of the PINK1/Parkin mitophagy pathway is associated with the enhanced M2 polarization observed on these surfaces.
Silencing PINK1/Parkin using siRNA prevents the surface-induced M2 polarization, indicating its critical role.
Under inflammatory conditions induced by lipopolysaccharide, anodized surfaces partially restore M2 polarization and mitophagy activation compared to polished controls.
Pharmacological activation of mitophagy with rapamycin enhances M2 polarization and improves osseointegration in inflammatory environments.
Validation in a rat model shows that rapamycin-enhanced bone integration is significantly reduced when PINK1/Parkin signaling is knocked down.

Simplified

A controlled inflammatory response, particularly the timely transition from pro-inflammatory (M1) to pro-regenerative (M2) macrophages, is crucial for successful osseointegration of titanium (Ti) implants. However, the intracellular mechanisms regulating this phenotypic switch remain unclear. Given the close interplay between inflammation and mitochondrial dysfunction, we investigated the role of PINK1/Parkin-dependent mitophagy in macrophage polarization at the Ti implants interface. Micro-/nanostructured Ti surfaces, including sandblasted/acid-etched (SLA) and anodized (AO) surfaces, were evaluated in comparison with polished (PT) controls. Both SLA and AO surfaces promoted M2 macrophage polarizationand, accompanied by upregulation of the PINK1/Parkin mitophagy pathway. Silencingusing siRNA abolished surface-induced M2 polarization, demonstrating the essential role of PINK1/Parkin-dependent mitophagy in this process. Under lipopolysaccharide (LPS)- induced inflammatory conditions, AO surfaces partially restored M2 polarization and mitophagy activation compared to PT controls. However, this effect alone was insufficient to fully overcome inflammation-mediated suppression. Pharmacological activation of mitophagy using rapamycin (RAPA) further enhanced M2 polarization, promoted osteogenic differentiation and significantly improved osseointegration under inflammatory conditions.validation using a rat distal femur implantation model demonstrated that RAPA-enhanced bone integration was markedly attenuated byknockdown, confirming the mechanistic dependence on PINK1/Parkin signaling. These findings identify PINK1/Parkin-dependent mitophagy as a critical intracellular regulator of macrophage polarization and-implant immune balance and highlight mitophagy activation as a promising therapeutic strategy to enhance Ti implant osseointegration in inflammatory microenvironments. in vitro in vivo Pink1In vivo Pink1peri

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How mitochondrial cleanup by PINK1/Parkin influences immune cell behavior and titanium implant integration during inflammation

Abstract

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