Poor angiogenesis and bony ingrowth are the major factors causing unsatisfactory healing between the tendon graft and the bone tunnel surface. Exogenous biological factors, biomaterials, and cells have been considered as new strategies to promote healing quality in recent years. However, it remains challenging for their clinical use because of insufficient in-situ retention time and release efficiency. Increasing attention has been paid to the hydrogel microspheres (HMPs) as potential drug-loading deliveries in biomedicine due to their minimally invasive manner, extended drug retention time, and high loading efficiency. In this review, the healing mechanism between the tendon graft and the bone tunnel is introduced, which is followed by a brief summarization of current methods applied for enhancement of the healing quality. Then, the preclinical studies focusing on HMPs as novel drug carriers are summarized to address the aforementioned concerns in the treatment of tendon-bone healing. Of note, the challenges and perspectives of HMPs in clinical conversion are also outlooked. Collectively, this review may inspire researchers and clinicians to develop clinical available HMPs in orthopedics such as sports medicine from both material and biomedical aspects.
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