Bi-lineage inducible and immunoregulatory electrospun fibers scaffolds for synchronous regeneration of tendon-to-bone interface

Facilitating regeneration of the tendon-to-bone interface can reduce the risk of postoperative retear after rotator cuff repair. Unfortunately, undesirable inflammatory responses following injury, difficulties in fibrocartilage regeneration, and bone loss in the surrounding area are major contributors to suboptimal tendon-bone healing. Thus, the development of biomaterials capable of regulating macrophage polarization to a favorable phenotype and promoting the synchronous regeneration of the tendon-to-bone interface is currently a top priority. Here, strontium-doped mesoporous bioglass nanoparticles (Sr-MBG) were synthesized through a modulated sol-gel method and Bi-lineage Inducible and Immunoregulatory Electrospun Fibers Scaffolds (BIIEFS) containing Sr-MBG were fabricated. The BIIEFS were biocompatible, showed sustained release of multiple types of bioactive ions, enhanced osteogenic and chondrogenic differentiation of mesenchymal stem cells (MSCs), and facilitated macrophage polarization towards the M2 phenotype in vitro. The implantation of BIIEFS at the torn rotator cuff resulted in greater numbers of M2 macrophages and the synchronous regeneration of tendon, fibrocartilage, and bone at the tendon-to-bone interface, leading to a significant improvement in the biomechanical strength of the supraspinatus tendon-humerus complexes. Our research offers a feasible strategy to fabricate immunoregulatory and multi-lineage inducible electrospun fibers scaffolds incorporating bioglass nanoparticles for the regeneration of soft-to-hard tissue interfaces

Regulating Macrophages through Immunomodulatory Biomaterials Is a Promising Strategy for Promoting Tendon-Bone Healing

The tendon-to-bone interface is a special structure connecting the tendon and bone and is crucial for mechanical load transfer between dissimilar tissues. After an injury, fibrous scar tissues replace the native tendon-to-bone interface, creating a weak spot that needs to endure extra loading, significantly decreasing the mechanical properties of the motor system. Macrophages play a critical role in tendon-bone healing and can be divided into various phenotypes, according to their inducing stimuli and function. During the early stages of tendon-bone healing, M1 macrophages are predominant, while during the later stages, M2 macrophages replace the M1 macrophages. The two macrophage phenotypes play a significant, yet distinct, role in tendon-bone healing. Growing evidence shows that regulating the macrophage phenotypes is able to promote tendon-bone healing. This review aims to summarize the impact of different macrophages on tendon-bone healing and the current immunomodulatory biomaterials for regulating macrophages, which are used to promote tendon-bone healing. Although macrophages are a promising target for tendon-bone healing, the challenges and limitations of macrophages in tendon-bone healing research are discussed, along with directions for further research