Regenerative Strategies in Avascular Necrosis: Stem Cells, Scaffolds, Exosomes, and Emerging Therapies

Avascular necrosis (AVN) is a condition that affects bones due to reduced blood supply. This leads to the death of osteocytes, the weakening of bone structure, and eventually joint collapse, with the femoral head being the most commonly impacted area. Traditional treatments, including medications and surgical options like core decompression and total joint replacement, often do not effectively repair damaged bone and can lead to significant complications. As a result, regenerative medicine has emerged as a hopeful alternative that focuses on biological repair and restoring function to necrotic bone. This review examines recent progress in regenerative strategies for AVN, emphasizing therapies based on stem cells, scaffold-guided tissue engineering, and new acellular methods. Mesenchymal stem cells (MSCs) from bone marrow, adipose tissue, and umbilical cord have strong abilities to promote bone growth and blood vessel formation through both differentiation and signaling processes. Clinical studies show that implanting autologous MSCs in the early stages of AVN can decrease pain, promote bone healing, and slow the disease’s progression. Improvements in biomaterial scaffolds, including natural, synthetic, and composite systems, have also enhanced cell survival, mechanical strength, and the controlled release of vital molecules. Additionally, growth factors, platelet-rich plasma, and exosomes from stem cells are gaining interest as additional or alternative treatment options. Even with positive results, challenges like low cell survival, immune system reactions, regulatory hurdles, and high costs still exist. Future advancements that include gene-modified stem cells, smart materials, and large-scale clinical trials are expected to refine regenerative treatments and enhance their application in clinical settings.