Advanced strategies for constructing interfacial tissues of bone and tendon/ligament

Abstract

Enthesis, the interfacial tissue between a tendon/ligament and bone, exhibits a complex histological transition from soft to hard tissue, which significantly complicates its repair and regeneration after injury. Because traditional surgical treatments for enthesis injury are not satisfactory, tissue engineering has emerged as a strategy for improving treatment success. Rapid advances in enthesis tissue engineering have led to the development of several strategies for promoting enthesis tissue regeneration, including biological scaffolds, cells, growth factors, and biophysical modulation. In this review, we discuss recent advances in enthesis tissue engineering, particularly the use of biological scaffolds, as well as perspectives on the future directions in enthesis tissue engineering.

Nanofibrous scaffolds for the healing of the fibrocartilaginous enthesis: advances and prospects

“…42,43 Each region exhibits unique characteristics in terms of cell type, ECM, collagen arrangement, and mineralization, which helps to effectively transmit stress and promote mutual fixation of bone and soft tissue grafts. 5,14,44 The main component of ECM in tendon/ligament area is type I collagen (Col I) (about 60-85% of its dry weight), and the rest is composed of proteoglycan, glycosaminoglycan (GAG), glycoprotein, and other collagen subtypes. 45 Non-mineralized fibrocartilage is rich in type II collagen, with high levels of type III collagen, and a small amount of type I and X collagen, decorin, and polysaccharides.…”

“…47 In the early stage of fibrocartilaginous enthesis injury, the levels of inflammatory factors such as interleukin (IL)-1b, IL-6, IL-8, tumor necrosis factor (TNF), matrix metalloproteinase (MMP)-1, MMP-3, and MMP-13 have been reported to be upregulated. 14 At the same time, the release of chemokines (including vascular endothelial growth factor (VEGF), transforming growth factor beta (TGF-b), and platelet-derived growth factor (PDGF)) at the fibrocartilaginous enthesis recruits fibroblasts, which in turn recruit neutrophils, macrophages, and osteoclasts to the injury site to repair the damaged tendons, ligaments, fibrocartilage, and bone. 48 However, excessive production of reactive oxygen species (ROS) by immune cells during the inflammatory stage can cause fibrosis at the enthesis, leading to the formation of excessive scar tissue and poor biomechanical properties.…”

“…During the rapid proliferative phase, fibroblasts, fibroblasts, fibrochondrocytes, osteocytes, and vascular endothelial cells proliferate rapidly, and fibroblasts produce collagen type III (the major component of scar tissue). 14,51 It has been suggested that TGF-b1 reaches peak levels at this stage and is abundant in fibrous scar tissue. 52 This may be a therapeutic target to prevent scar tissue formation.…”

“…As is known, the natural healing process of the injury is complex, including inflammation, rapid proliferation, and gradual remodeling. 14 Although musculoskeletal tissue has natural self-healing ability, its efficiency is relatively low. 16 Therefore, improving the healing of fibrocartilaginous enthesis poses great challenges.…”

“…12,13 Surgical repair and reconstruction typically only restore the anatomical structure of the fibrocartilaginous enthesis, and the scar tissue formed after healing lacks natural gradient structure and collagen fiber arrangement, resulting in poor mechanical properties that do not promote fibrocartilaginous enthesis regeneration. 14,15 In addition, some non-surgical therapies also have limitations. As is known, the natural healing process of the injury is complex, including inflammation, rapid proliferation, and gradual remodeling.…”