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Enthesis is a structurally complex and functionally critical interface connecting tendon and bone that plays an essential role in maintaining integrity of the shoulder joint. Despite the availability of advanced surgical procedures for rotator cuff repair, there is a high rate of failure following surgery due to suboptimal enthesis healing and regeneration. Novel strategies based on tissue engineering are gaining popularity in improving tendon-bone interface (TBI) regeneration. Through incorporating physical and biochemical cues into scaffold design which mimics the structure and composition of native enthesis is advantageous to guide specific differentiation of seeding cells and facilitate the formation of functional tissues. In this review, we summarize the current state of research in enthesis tissue engineering highlighting the development and application of biomimetic scaffolds that replicate the gradient TBI. We also discuss the latest techniques for fabricating potential translatable scaffolds such as 3D bioprinting and microfluidic device. While preclinical studies have demonstrated encouraging results of biomimetic gradient scaffolds, the translation of these findings into clinical applications necessitates a comprehensive understanding of their safety and long-term efficacy.<\/jats:p>","DOI":"10.1088\/1758-5090\/ad467d","type":"journal-article","created":{"date-parts":[[2024,5,2]],"date-time":"2024-05-02T18:27:11Z","timestamp":1714674431000},"page":"032005","update-policy":"https:\/\/doi.org\/10.1088\/crossmark-policy","source":"Crossref","is-referenced-by-count":27,"title":["Biomimetic gradient scaffolds for the tissue engineering and regeneration of rotator cuff enthesis"],"prefix":"10.1088","volume":"16","author":[{"given":"Yang","family":"Chen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yexin","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weihong","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6906-5350","authenticated-orcid":true,"given":"Qian","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"266","published-online":{"date-parts":[[2024,5,15]]},"reference":[{"key":"bfad467dbib1","doi-asserted-by":"publisher","first-page":"1954","DOI":"10.1016\/S0140-6736(22)00652-3","article-title":"Subacromial balloon spacer for irreparable rotator cuff tears of the shoulder (START:REACTS): a group-sequential, double-blind, multicentre randomised controlled trial","volume":"399","author":"Metcalfe","year":"2022","journal-title":"Lancet"},{"key":"bfad467dbib2","doi-asserted-by":"publisher","first-page":"208","DOI":"10.1177\/03635465211054512","article-title":"Rotator cuff tear size regulates fibroadipogenic progenitor number and gene expression profile in the supraspinatus independent of patient age","volume":"50","author":"Davies","year":"2022","journal-title":"Am. 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