Clinical Significance

The Growing Challenge of MRONJ: Addressing a Critical Clinical Need

As Singapore's population ages, the use of anti-resorptive drugs such as bisphosphonates for osteoporosis and metastatic bone disease continues to rise. While highly effective, these medications can lead to Medication-Related Osteonecrosis of the Jaw (MRONJ), a debilitating condition characterized by persistent exposed jawbone and impaired healing following dental procedures such as tooth extraction. 

The Science of the Disease: Immune Dysregulation

Recent research highlights that MRONJ is driven by impaired bone turnover and a "cytokine storm" resulting from immune system dysfunction. Anti-resorptive agents disrupt the balance of macrophages, which are essential for healing. Specifically, these drugs increase the polarization of M1 macrophages (pro-inflammatory) while decreasing the polarization of M2 macrophages (pro-healing). This creates a chronic, highly inflammatory environment that prevents angiogenesis and leads to bone necrosis.

The Clinical Gap: Why New Solutions Are Needed

Managing MRONJ is exceptionally difficult because it often remains asymptomatic for long periods, leading to underdiagnosis until it reaches advanced stages. Current care is largely palliative, relying on:Antibiotics and Antimicrobials: These manage pain and infection but do not treat the underlying necrotic bone.Surgical Intervention: Removing necrotic bone can help, but these invasive methods risk introducing additional trauma to an already compromised area. Furthermore, comorbid factors like diabetes or corticosteroid use can further impair the body's innate immune response, decreasing the likelihood of successful healing. 

Smart Piezoelectric Scaffolds for Bone Regeneration and MRONJ Prevention

Bone healing is regulated not only by bone-forming cells but also by the immune system. Macrophages, key immune cells involved in inflammation and tissue repair, play a critical role in determining whether healing progresses successfully. Recent advances in biomaterials have demonstrated that electrical stimulation can influence macrophage behavior, reduce inflammation, and enhance bone regeneration. Our research focuses on developing next-generation ultrasound-activated piezoelectric scaffolds that generate localized electrical signals in response to mechanical stimulation. These “smart” biomaterials actively modulate the immune environment while promoting bone formation, offering a new approach to regenerative medicine.