Biomimetic strategies for tendon/ligament-to-bone interface regeneration

Abstract

Tendon/ligament-to-bone healing poses a formidable clinical challenge due to the complex structure, composition, cell population and mechanics of the interface. With rapid advances in tissue engineering, a variety of strategies including advanced biomaterials, bioactive growth factors and multiple stem cell lineages have been developed to facilitate the healing of this tissue interface. Given the important role of structure-function relationship, the review begins with a brief description of enthesis structure and composition. Next, the biomimetic biomaterials including decellularized extracellular matrix scaffolds and synthetic-/natural-origin scaffolds are critically examined. Then, the key roles of the combination, concentration and location of various growth factors in biomimetic application are emphasized. After that, the various stem cell sources and culture systems are described. At last, we discuss unmet needs and existing challenges in the ideal strategies for tendon/ligament-to-bone regeneration and highlight emerging strategies in the field.

A Dual-Factor Releasing Hydrogel for Rotator Cuff Injury Repair

“…The normal tendon-bone interface consists of four layers of tissue, which are the tendon, fibrous tissue, fibrocartilage, and bone tissue in turn (Atesok et al, 2014;Patel et al, 2018;Lei et al, 2021). The arrangement of the four layers of tissue can disperse the stress of tendon and bone tissue, thus enhancing the strength of the tendon-bone interface.…”

“…The arrangement of the four layers of tissue can disperse the stress of tendon and bone tissue, thus enhancing the strength of the tendon-bone interface. Fibrocartilage is an important structure to maintain mechanical stability of the tendon-bone interface at the early stage of tendon-bone healing (Atesok et al, 2014;Patel et al, 2018;Lei et al, 2021). Accelerating the regeneration of fibrocartilage is important to promote rotator cuff healing (Zhu et al, 2021).…”

Engineering an enthesis-like graft for rotator cuff repair: An approach to fabricate highly biomimetic scaffold capable of zone-specifically releasing stem cell differentiation inducers

“…To realize that, the biomimicry and bioactivity of scaffolds are deemed to be the most critical. To date, tissue engineers and biomaterial scientists have developed some scaffolds with bionic and functional characteristics using polymers (both natural and synthetic), ceramics or most commonly a combination of them (composites) [ 14 ]. However, these scaffolds are still not highly mimic normal enthesis in morphology and composition, at the same time, satisfying the adequate mechanical needs.…”

Fibrous Polymer-Based Composites Obtained by Electrospinning for Bone Tissue Engineering

“…Over the past few decades, an approach aimed at formation of new tissues with required functions by isolation and expansion of target donor cells in vitro for their further seeding and growth in implanted constructions has become widespread, and received more study against the background of other ways to eliminate tissue damages [ 1 ]. Currently, the use of such a cellular approach in relation to bone, cartilage, tendon, and ligament tissues, among others, demonstrates moderate success [ 2 ]. However, modern materials and techniques for their manufacturing still do not meet all the necessary requirements to be applied in the field of regenerative medicine.…”