Advances in Regenerative Sports Medicine Research

Abstract

Regenerative sports medicine aims to address sports and aging-related conditions in the locomotor system using techniques that induce tissue regeneration. It also involves the treatment of meniscus and ligament injuries in the knee, Achilles' tendon ruptures, rotator cuff tears, and cartilage and bone defects in various joints, as well as the regeneration of tendon-bone and cartilage-bone interfaces. There has been considerable progress in this field in recent years, resulting in promising steps toward the development of improved treatments as well as the identification of conundrums that require further targeted research. In this review the regeneration techniques currently considered optimal for each area of regenerative sports medicine have been reviewed and the time required for feasible clinical translation has been assessed. This review also provides insights into the direction of future efforts to minimize the gap between basic research and clinical applications.

Keywords: bone; cartilage; meniscus; regenerative medicine; rotator cuff; sports medicine; tendon-to-bone.

FIGURE 1

Sports medicine related injuries.

FIGURE 2

Orchestrated biomechanical, structural, and biochemical stimuli for engineering anisotropic meniscus. (A) Schematic diagrams for reconstruction of functional anisotropic meniscus; (B) Gross view and low-magnification immunofluorescence (IF) images of native or regenerated menisci at 24 weeks after in vivo implantation in rabbit knees. Green, COL-1; red, COL-2. Copyright 2019 American Association for the Advancement of Science.

FIGURE 3

Electrodeposition of calcium phosphate onto polyethylene terephthalate artificial ligament enhances graft-bone integration after anterior cruciate ligament reconstruction. (A) Electrodeposition of calcium phosphate onto polyethylene terephthalate artificial ligament; (B) The viability and SEM morphology of MC3T3-E1 in the PET, PET/BM-CaP and PET/ED-CaP groups; (C) Micro-CT analysis of the PET, PET/BM-CaP and PET/ED-CaP groups at 12 weeks after surgery; (D) Masson and toluidine blue staining results of pathological sections in the PET, PET/BM-CaP and PET/ED-CaP groups at 6 and 12 weeks after surgery. Copyright 2021 Elsevier.

FIGURE 4

Therapeutic potential of hAECs for early Achilles tendon defect repair through regeneration. (A) Circular defects of 5 mm created in the Achilles tendons. One defect was filled with fibrin glue, whereas the contralateral with 10 × 106 PKH26-stained cells suspended in fibrin glue (bottom); (B) Representative haematoxylin–eosin-, Herovici and immunofluorescent staining of CTR (control) and human amniotic epithelial cell (hAEC)-treated tendons. (C) Key functions associated with genes found to be up-regulated in hAECs and the top-scored network; (D) Key functions associated with genes found to be down-regulated in hAECs and the top-scored network. Copyright 2017 Wiley.

FIGURE 5

Functional decellularized fibrocartilaginous matrix graft for rotator cuff enthesis regeneration: A novel technique to avoid in-vitro loading of cells. (A) Developing a cell-free graft with chemotaxis to recruit postoperative injected cells; (B) Macroscopic observation, histological analysis, and synchrotron radiation-Fourier transform infrared spectroscopy analysis of the book-type nature fibrocartilage tissues and C-SDF-1α/BDFM, sections stained with hematoxylin and eosin (H&E), DAPI, toluidine blue (TB), and picrosirius red (PR); (C,D) Histological analyses of regenerated fibrocartilage during RC healing. Copyright 2020 Elsevier.

FIGURE 6

3D printing of a lithium-calcium-silicate crystal bioscaffold with dual bioactivities for osteochondral interface reconstruction. (A) Schematic illustration of application of Li2Ca4Si4O13 scaffolds for osteochondral reconstruction; (B) SEM images of 3D-printed Li₂Ca₄Si₄O₁₃ scaffolds after fabrication and (C) after soaking in the simulated body fluids for 14 days; Macro-photographs showed the defects in the control group and the other two experimental groups (D ₁ : blank control without scaffolds, E ₁ : pure β-TCP scaffolds, F ₁ : Li₂Ca₄Si₄O₁₃ scaffolds) at 12 weeks of post-surgery; (D₂ – F₂) showed 2D projection images of the three experimental groups at week 12; (D₃ – F₃) showed the transverse view of 3D reconstruction images of the three experimental groups at week 12; (D₄ – F₄) showed the sagittal view of 3D reconstruction images of the three experimental groups at week 12. Copyright 2019 Elsevier.

FIGURE 7

Vascularized 3D printed scaffolds for promoting bone regeneration. (A) Schematic diagram of bridging deferoxamine (DFO) on the surface of 3D printed polycaprolactone (PCL) scaffold and its biological function for bone regeneration in bone defect model; (B) Micro-CT analysis of the effect of scaffolds on bone repair in vivo; (C) Representative images of hematoxylin-eosin (HE) staining of the decalcificated bones slice, showing the new formed tissue including the fibrous tissue (F), newly mineralized bone tissue (NB) and the structure of scaffolds (S). Copyright 2019 Elsevier.

FIGURE 8

Crimped nanofiber scaffold mimicking tendon-to-bone interface for fatty-infiltrated massive rotator cuff repair. (A) Schemata of fabrication of the crimped nanofibrous scaffold for massive rotator cuff tear repairing; (B) Representative micro-computed tomography (micro-CT) images of the proximal humerus and quantitative analysis. Copyright 2022 Elsevier.