Amorphous calcium phosphate nanoparticles using adenosine triphosphate as an organic phosphorus source for promoting tendon–bone healing

Abstract

Background: Rotator cuff tear (RCT) is a common problem of the musculoskeletal system. With the advantage of promoting bone formation, calcium phosphate materials have been widely used to augment tendon-bone healing. However, only enhancing bone regeneration may be not enough for improving tendon–bone healing. Angiogenesis is another fundamental factor required for tendon–bone healing. Therefore, it’s necessary to develop a convenient and reliable method to promote osteogenesis and angiogenesis simultaneously, thereby effectively promoting tendon–bone healing. Methods: The amorphous calcium phosphate (ACP) nanoparticles with dual biological activities of osteogenesis and angiogenesis were prepared by a simple low-temperature aqueous solution method using adenosine triphosphate (ATP) as an organic phosphorus source. The activities of osteogenesis and angiogenesis and the effect on the tendon–bone healing of ACP nanoparticles were tested in vitro and in a rat model of acute RCT. Results: The ACP nanoparticles with a diameter of tens of nanometers were rich in bioactive adenosine. In vitro, we confirmed that ACP nanoparticles could enhance osteogenesis and angiogenesis. In vivo, radiological and histological evaluations demonstrated that ACP nanoparticles could enhance bone and blood vessels formation at the tendon–bone junction. Biomechanical testing showed that ACP nanoparticles improved the biomechanical strength of the tendon–bone junction and ultimately promoted tendon–bone healing of rotator cuff. Conclusions: We successfully confirmed that ACP nanoparticles could promote tendon–bone healing. ACP nanoparticles are a promising biological nanomaterial in augmenting tendon–bone healing. Graphic abstract: [Figure not available: see fulltext.]