To evaluate the therapeutic effect and potential mechanism of action of embryonic stem cell-derived immunity and matrix regulatory cells （IMRC） on traumatic heterotopic ossification （THO）.

A THO model was established via Achilles tendon injury in SD rats， which were then randomly divided into a sham operation group， a control group， and an IMRC treatment group. The IMRC group received local injections of a suspension containing 1×10⁶ IMRCs twice weekly for 4 weeks post-operation. At 4， 8， and 12 weeks post-surgery， heterotopic bone volume and bone mineral density （BMD） were quantitatively analyzed using micro-computed tomography (Micro-CT). Tissue inflammation， fibrosis， and heterotopic bone formation were assessed via haematoxylin-eosin stain and Masson staining. The protein expression levels of α-smooth muscle actin （α-SMA） and osteocalcin （OCN） were detected by immunohistochemistry. Safety was evaluated by monitoring body weight and examining the pathology of major organs.

Compared to the control group， IMRC treatment significantly inhibited heterotopic bone formation. Micro-CT revealed that at 12 weeks post-operation， the heterotopic bone volume in the IMRC group [（16.67±0.90） mm³] was reduced by 79.5% compared to the control group [（81.42±2.72） mm³] （P<0.001）， and the BMD was also significantly lower [（223.78±16.65） mg/cm³ vs （595.14±30.31） mg/cm³， P<0.001]. Histological analysis showed significant reductions in inflammatory cell infiltration， collagen deposition， and fibrosis scores in the IMRC group （all P<0.01）， alongside markedly suppressed expression of α-SMA and OCN （all P<0.01）. All rats exhibited steady body weight gain， and no pathological changes were observed in the major organs， indicating a favorable safety profile for IMRC treatment.

Local injection of IMRC can safely and effectively inhibit the development and progression of THO through a multi-mechanism approach involving anti-inflammation， anti-fibrosis， and inhibition of osteogenesis， representing a novel cell therapy strategy with broad translational potential.