Biophysical stimulation of bone and cartilage: state of the art and future perspectives. Author: Massari L1, Benazzo F2, Falez F3, Perugia D4, Pietrogrande L5, Setti S6, Osti R7, Vaienti E8, Ruosi C9, Cadossi R6 Affiliation: <sup>1</sup>University of Ferrara, Via Vigne 4, 44121, Ferrara, Italy. msl@unife.it. <sup>2</sup>IRCCS Foundation "San Matteo" Hospital, University of Pavia, 27100, Pavia, Italy. <sup>3</sup>Santo Spirito in Sassia Hospital, 00193, Rome, Italy. <sup>4</sup>La Sapienza University, 00185, Rome, Italy. <sup>5</sup>San Paolo Hospital, University of Milan, 20142, Milan, Italy. <sup>6</sup>IGEA Clincal Biophysics, 41012, Carpi, MO, Italy. <sup>7</sup>Osti Clinic, 44121, Ferrara, Italy. <sup>8</sup>University of Parma, 43100, Parma, Italy. <sup>9</sup>Federico II University Naples, 80100, Naples, Italy. Conference/Journal: Int Orthop. Date published: 2019 Jan 15 Other: Special Notes: doi: 10.1007/s00264-018-4274-3. [Epub ahead of print] , Word Count: 286 INTRODUCTION: Biophysical stimulation is a non-invasive therapy used in orthopaedic practice to increase and enhance reparative and anabolic activities of tissue. METHODS: A sistematic web-based search for papers was conducted using the following titles: (1) pulsed electromagnetic field (PEMF), capacitively coupled electrical field (CCEF), low intensity pulsed ultrasound system (LIPUS) and biophysical stimulation; (2) bone cells, bone tissue, fracture, non-union, prosthesis and vertebral fracture; and (3) chondrocyte, synoviocytes, joint chondroprotection, arthroscopy and knee arthroplasty. RESULTS: Pre-clinical studies have shown that the site of interaction of biophysical stimuli is the cell membrane. Its effect on bone tissue is to increase proliferation, synthesis and release of growth factors. On articular cells, it creates a strong A2A and A3 adenosine-agonist effect inducing an anti-inflammatory and chondroprotective result. In treated animals, it has been shown that the mineralisation rate of newly formed bone is almost doubled, the progression of the osteoarthritic cartilage degeneration is inhibited and quality of cartilage is preserved. Biophysical stimulation has been used in the clinical setting to promote the healing of fractures and non-unions. It has been successfully used on joint pathologies for its beneficial effect on improving function in early OA and after knee surgery to limit the inflammation of periarticular tissues. DISCUSSION: The pooled result of the studies in this review revealed the efficacy of biophysical stimulation for bone healing and joint chondroprotection based on proven methodological quality. CONCLUSION: The orthopaedic community has played a central role in the development and understanding of the importance of the physical stimuli. Biophysical stimulation requires care and precision in use if it is to ensure the success expected of it by physicians and patients. KEYWORDS: Biophysical stimulation; Bone tissue; CCEF; Cartilage; LIPUS; PEMF PMID: 30645684 DOI: 10.1007/s00264-018-4274-3