Figure 5.

Challenges of enthesis and its regeneration (challenges within exploring physiological entheses are shown in (a) and (b). (a) Inadequate microscopic observation techniques, insufficient understanding of fiber direction, mineral distribution, complexity of fibers’ migration and obstacles in sample preparation. (b) Barriers in exploring mechanisms of embryogenesis, healing and regulation progress and few markers of three stages. Challenges within constructing engineering enthesis are shown in (c) and (d). (c) Obstacles in ensuring safety involving toxic and side effects, possible immune concerns, uncertain biodegradation rate in vivo and surgical operation risks. (d) Little knowledge of mechanical stimuli and factor stimuli, complex factor delivery, lack of techniques to edit the surface of fiber and mechanical properties of biomaterials. Challenges within clinical trials and commercialization are shown in (e). (e) Few insecure cell sources, incomplete animal model system and a lack of suitable ancillary drugs in clinical trials. (Lack of effective strategies for transplantation, postoperative monitoring and marketization of products.)