Comparative effects of platelets and plasma-derived mitochondria in early-phase Achilles tendon inflammation

Tendon repair often results in a scar-like extracellular matrix rather than the restoration of native architecture. Early inflammatory remodeling may be a critical determinant of outcome, and monocyte/macrophage-associated programs are prominent during this window. Motivated by prior in vitro observations that platelets and plasma-derived mitochondria (p-mito) are associated with divergent macrophage signatures, we tested their effects in a collagenase-induced rat Achilles tendon injury model. Rats received intratendinous injections of platelets or p-mito on Day 3 post-induction and were analyzed at a Day 10 endpoint. Platelet treatment was associated with an additional transient increase in tendon thickness, whereas p-mito were associated with a sustained post-treatment decline approaching saline-injected sham levels by later assessments. At Day 10, p-mito were associated with the lower operational M1/M2 ratio, lower TNF-α and IL-6 with higher IL-10, and a tendon protein profile characterized by higher type I collagen (COL1) with lower tenascin C relative to platelets. Together, these findings indicate that p-mito are associated with distinct inflammatory and tendon-marker profiles relative to a platelet preparation. These observations suggest that p-mito may represent a mechanistically distinct acellular alternative to the platelet-based preparation used here, with the potential to limit transient inflammatory flare.