Injection of a PMMA-doped MSC spheroid gel for the treatment of painful osteoporotic vertebral compression fractures

We aimed to develop a biocompatible treatment to overcome the limitations of polymethyl methacrylate (PMMA) vertebroplasty for osteoporotic compression fracture patients. We synthesized an injectable hydrogel containing PMMA. Mesenchymal stem cell (MSC) spheroids were included in the injectable PMMA-doped gel (= PMMA-doped spheroid gel). In vitro, the osteogenic/anti-inflammatory effects of the embedded spheroids were investigated by the quantitative real-time polymerase chain reaction method. In vivo, we used ovariectomy (OVX)-induced osteoporotic rats with injured femurs to investigate the pain-relief effects. The OVX rats were divided into four groups according to the materials injected (non, PMMA, PMMA gel, and PMMA-spheroid gel) into the lesion. The immunofluorescence (IF) intensity levels of painful markers in dorsal root ganglia (DRG) were measured. In vitro, a volumetric ratio of the gel of 8 (gel):2 (PMMA) was non-cytotoxic for MSCs and promoted the expression of osteogenic/anti-inflammatory markers. In vivo, the values of several bone parameters in the PMMA-doped spheroid gel group showed remarkable increases compared to those in the PMMA group. In addition, the IF intensity levels of the painful markers were noticeably decreased in the PMMA-spheroid gel group. We, therefore, suggest that this treatment can be useful for osteoporotic vertebral compression fracture patients.

Automated summary

This study aimed to develop a biocompatible treatment using an injectable hydrogel containing PMMA to overcome the limitations of PMMA vertebroplasty for osteoporotic compression fracture patients. MSC spheroids were included in the gel to investigate their osteogenic/anti-inflammatory effects in vitro, and the pain-relief effects were investigated in ovariectomy-induced osteoporotic rats with injured femurs. The results showed that the PMMA-doped spheroid gel had positive effects on osteogenesis and pain relief, suggesting its potential usefulness for osteoporotic vertebral compression fracture patients.