Biomimetic Nanoparticles for Bone Regeneration: Construction Strategies and Therapeutic Mechanisms

Zehua Wang,1,2,* Ning Shen,3,* Tao Yang,2,* Shuhang Dong,1,2,* Kaige Xu,1 Kunyi Zhao,1 Yingze Zhang,1,4 Yaping Jiang,5 Tao Li1 1Department of Joint Surgery, The Affiliated Hospital of Qingdao University, Qingdao, 266003, People’s Republic of China; 2Department of Clinical Medicine, Qingdao Medical College of Qingdao University, Qingdao, 266003, People’s Republic of China; 3Institute of Cancer Stem Cell, Dalian Medical University, Dalian, 116044, People’s Republic of China; 4Department of Orthopedics, The Third Hospital of Hebei Medical University, Shijiazhuang, 050000, People’s Republic of China; 5Department of Oral Implantology, The Affiliated Hospital of Qingdao University, Qingdao, 266003, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yaping Jiang, Department of Oral Implantology, The Affiliated Hospital of Qingdao University, Qingdao, 266003, People’s Republic of China, Email [email protected] Tao Li, Department of Joint Surgery, The Affiliated Hospital of Qingdao University, No. 59, Haier Road, Qingdao, 266000, People’s Republic of China, Email [email protected]: Bone tissue is the hardest and most dynamic connective tissue in the human body, and its integrity is essential for maintaining both mechanical support and physiological functions. However, with the aging population, the incidence of fractures, osteoporosis, and bone defects has risen significantly, severely impairing patients’ quality of life and creating a substantial social burden. Although autologous or allogeneic bone grafts and metallic or non-metallic implants can partially restore bone defects, their long-term efficacy is constrained by donor shortages, immune rejection, and limited regenerative capacity. Consequently, the development of efficient, precise, and biomimetic bone regeneration strategies is of great importance. In recent years, biomimetic nanoparticles have shown unique advantages in mimicking the bone microenvironment, delivering bioactive factors, and modulating cellular behavior due to their tunable structures and functions. This review summarizes the structural composition of bone tissue and its repair processes, highlights biomimetic nanoparticle construction strategies based on cell membranes, exosomes, proteins, and peptides, and discusses their roles in osteogenesis, mineralization, immune regulation, and neurovascular development. Finally, it explores their clinical translation prospects and associated challenges.Keywords: biomimetic nanoparticles, bone regeneration, exosomes, targeting, tissue engineering