Influences and strategies for bone regeneration based on microenvironment pH adjustment

Bone possesses remarkable endogenous regenerative capacity. Bone regeneration is typically divided into three stages: inflammation, bone formation, and bone remodeling, during which pH is a critical variable. The influence of pH on the bone regeneration process depends on three main factors: (1) the activity and differentiation of cells involved in bone regeneration are affected by pH; (2) protein activity is regulated by pH; and (3) extracellular calcium phosphate precipitates in a pH-dependent manner. The aim of this study is to review the mechanisms by which microenvironment pH affects bone regeneration and to explore specific sites and signaling pathways involved in pH regulation during the bone regeneration process. Therapeutic approaches aimed at enhancing bone regeneration via modulation of microenvironment pH are discussed, including pH adjustment via biological implant materials, pH-responsive material setting, and pH stabilization through anti-inflammatory therapy. Investigating the impact of microenvironment pH on bone regeneration is of considerable clinical importance, as it provides valuable insights for improving the success rates of bone implants and promoting bone healing. This review offers insights into regulatory mechanisms, establishes theoretical foundations, and presents new perspectives for current research on bone defect repair.