Adipose Micro-Grafts Enhance Tendinopathy Healing in Ovine Model: An in Vivo Experimental Perspective Study

Abstract

In Europe, approximatively 100 000 to 500 000 tendon repairs are performed every year. These procedures are associated with a considerable rate of postoperative complications (from 6% to 11%). Autologous micro-grafts (AAMG) and stromal vascular fraction (SVF) have been shown to improve tendon healing in 60% to 70% of treated rodents. The purpose of this study was to evaluate the effects of AAMG in a sheep model with tendinopathy. We used sheep models because, as a large animal, they are more comparable to humans. The hypothesis was that SVF injection would improve tendon healing compared with the control group, reducing inflammatory and matrix degrading, while increasing anti-inflammatory expression and collagen synthesis in the early stage of tendon injury. Sixteen Apennine sheep aged 2 to 5 years underwent 500 UI type I collagenase injection into both common calcaneal tendons (CCT) to induce tendinopathy. After 15 days (T0), one CCT in every ovine underwent randomly to 2.5 mL of AAMG obtained by mechanical disruption and the contralateral CCTs received no treatment. Clinical, ecographic, and sonographic evaluations were performed after 4 weeks (T1) and 8 weeks (T2). Histological, immunohistochemical, real-time polymerase chain reaction (RT-PCR), and biomechanical evaluations were performed at T2. At T2, the treated group showed a final tendon diameter (9.1 ± 1.4 mm) and a hardness expression (62%) that were similar to the original healthy tendon (8.1 ± 1.1 mm; 100%), with a significant recovery compared with the control group (9.5 ± 1.7 mm; 39%). Moreover, histological analysis of the treated group revealed an improvement in the fiber orientation score, fiber edema score, infiltrative-inflammatory process, and necrosis score (4.3 ± 3.3) compared with control group (8.8 ± 2.9). Immunohistochemically, the treated group showed high expression of collagen 1, Factor

In Vitro Characterization of Canine Microfragmented Adipose Tissue Non-Enzymatically Extracted from the Thigh and Lumbar Regions

“…MSCs are located in the bone marrow, adipose tissue, synovial membrane and muscular tissue, exerting an immunosuppressive, anti-inflammatory, and antifibrotic effect. Tissue engineering considers adopting MSCs as an option for regenerating tissues, with reference to bone and cartilage, due to their ability to differentiate into multiple cytotypes, including chondrocytes and osteoblasts [ 18 , 19 ], but MSCs are also able to heal the damaged tendon [ 20 ]. Therefore, the “stromal vascular fraction” (SVF), which is mainly located around blood vessels, is a heterogeneous solution stemmed from adipose tissue and composed by adipose stem cells (ASCs), endothelial cells, and stromal cells.…”

Application of Orthobiologics in Achilles Tendinopathy: A Review

“…SVF, a product of adipose tissue, carries a wide variety of cells, including endothelial cells, preadipocytes, type 2 macrophages, T cells, pericytes as well as mesenchymal stromal/stem and progenitor cells [ 89 , 90 , 94 ]. The application of SVF for the treatment of tendinopathies, specifically, yields satisfactory regenerative outcomes [ 95 , 96 , 97 , 98 ]. An in vivo study with SVF and AD-MSCs demonstrates the maintenance and induction of tendon fiber organization [ 96 ].…”

“…The application of SVF for the treatment of tendinopathies, specifically, yields satisfactory regenerative outcomes [ 95 , 96 , 97 , 98 ]. An in vivo study with SVF and AD-MSCs demonstrates the maintenance and induction of tendon fiber organization [ 96 ]. Usuelli et al demonstrated that the intratendinous SVF injection exhibited faster recovery results at just 15 days after treatment for AT [ 95 ].…”

“…Usuelli et al demonstrated that the intratendinous SVF injection exhibited faster recovery results at just 15 days after treatment for AT [ 95 ]. Piccionello et al revealed the significant findings in the ovine model of tendinopathy [ 96 ]. Matrix composition and collagen deposits in treated tendons are significantly enriched, and neo-angiogenesis is improved within the lesion sites and it was concluded that the reorganization of tendon fibers is just as important as the proliferation, differentiation, and immunomodulatory capacities of SVF cells [ 96 ].…”

The Functions and Mechanisms of Low-Level Laser Therapy in Tendon Repair (Review)

“…Secondly, they downregulate relevant inflammatory factors, enhance fibroblast proliferation, accelerate tendon cell differentiation, and boost angiogenesis. Finally, they further spur tissue regeneration and boost the process of tendon repair ( Shen et al, 2020 ; Piccionello et al, 2021 ). While MSCs have considerable benefits in musculoskeletal disorders, there is still a certain risk of infection during the healing process.…”