Tendon injuries suffer from a slow healing, often ending up in fibrovascular scar formation, leading to inferior mechanical properties and even re-rupture upon resumption of daily work or sports. Strategies including the application of growth factors have been under view for decades. Insulin-like growth factor-1 (IGF-1) is one of the used growth factors and has been applied to tenocyte in vitro cultures as well as in animal preclinical models and to human patients due to its anabolic and matrix stimulating effects. In this narrative review, we cover the current literature on IGF-1, its mechanism of action, in vitro cell cultures (tenocytes and mesenchymal stem cells), as well as in vivo experiments. We conclude from this overview that IGF-1 is a potent stimulus for improving tendon healing due to its inherent support of cell proliferation, DNA and matrix synthesis, particularly collagen I, which is the main component of tendon tissue. Nevertheless, more in vivo studies have to be performed in order to pave the way for an IGF-1 application in orthopedic clinics.
One great challenge in surgical tendon repair is the minimization of peritendinous adhesions. An electrospun tube can serve as a physical barrier around a conventionally sutured tendon. Six New Zealand White rabbits had one Achilles tendon fully transsected and sutured by a 4-strand suture. Another six rabbits had the same treatment, but with the additional electrospun DegraPol tube set around the sutured tendon. The adhesion formation to the surrounding tissue was investigated 12 weeks post-operation. Moreover, inflammation-related protease-activated receptor-2 (PAR-2) protein expression was assessed. Finally, rabbit Achilles tenocyte cultures were exposed to platelet-derived growth factor-BB (PDGF-BB), which mimicks the tendon healing environment, where PAR-2 gene expression was assessed as well as immunofluorescent staining intensity for F-actin and α-tubulin, respectively. At 12 weeks post-operation, the partially degraded DegraPol tube exhibited significantly lower adhesion formation (− 20%). PAR-2 protein expression was similar for time points 3 and 6 weeks, but increased at 12 weeks post-operation. In vitro cell culture experiments showed a significantly higher PAR-2 gene expression on day 3 after exposure to PDGF-BB, but not on day 7. The cytoskeleton of the tenocytes changed upon PDGF-BB stimulation, with signs of reorganization, and significantly decreased F-actin intensity. An electrospun DegraPol tube significantly reduces adhesion up to twelve weeks post-operation. At this time point, the tube is partially degraded, and a slight PAR-2 increase was detected in the DP treated tendons, which might however arise from particles of degrading DegraPol that were stained dark brown. PAR-2 gene expression in rabbit tenocytes reveals sensitivity at around day 10 after injury.
Tendon injuries can result in two major drawbacks. Adhesions to the surrounding tissue may limit the range of motion, while fibrovascular scar formation can lead to poor biomechanical outcomes. Prosthetic devices may help to mitigate those problems. Emulsion electrospinning was used to develop a novel three-layer tube based on the polymer DegraPol (DP), with incorporated insulin-like growth factor-1 (IGF-1) in the middle layer. Scanning electron microscopy was utilized to assess the fiber diameter in IGF-1 containing pure DP meshes. Further characterization was performed with Fourier Transformed Infrared Spectroscopy, Differential Scanning Calorimetry, and water contact angle, as well as through the assessment of mechanical properties and release kinetics from ELISA, and the bioactivity of IGF-1 by qPCR of collagen I, ki67, and tenomodulin in rabbit Achilles tenocytes. The IGF-1-containing tubes exhibited a sustained release of the growth factor up to 4 days and showed bioactivity by significantly upregulated ki67 and tenomodulin gene expression. Moreover, they proved to be mechanically superior to pure DP tubes (significantly higher fracture strain, failure stress, and elastic modulus). The novel three-layer tubes intended to be applied over conventionally sutured tendons after a rupture may help accelerate the healing process. The release of IGF-1 stimulates proliferation and matrix synthesis of cells at the repair site. In addition, adhesion formation to surrounding tissue can be reduced due to the physical barrier.
Large bone defects after trauma demand for adequate bone substitutes. Bone void fillers should be antibacterial and pro-angiogenic. One viable option is the use of composite materials like the combination of PLGA and amorphous calcium phosphate (aCaP).
30 January 2024 in ACS Applied Materials & Interfaces
Tendon ruptures are common musculoskeletal injuries associated with prolonged healing and complications such as adhesion formation and rerupture. Despite advancements in treatment strategies, full functional recovery remains a challenge. Growth factors (GFs) like insulin-like growth factor-1 (IGF-1) and platelet-derived growth factor-BB (PDGF-BB) play key roles in tendon repair and may have synergistic effects when applied together. To support tendon healing, a bioactive electrospun polymer scaffold made of Degrapol® (DP) was developed, incorporating IGF-1, PDGF-BB, or both. A range of in vitro and in vivo analyses were performed to assess scaffold structure, cell behavior, gene expression, metabolism, and biomechanical and adhesion outcomes three weeks post-surgery. Interestingly, the combined application of IGF-1 and PDGF-BB did not simply amplify individual effects but showed a complex interaction. Depending on the parameter and time point, the combination led to either enhanced or reduced responses compared to single-factor treatments, indicating a synergistic modulation rather than a purely additive effect. These findings suggest that the combination of IGF-1 and PDGF-BB can modulate key cellular and molecular processes in tendon regeneration, making this approach a promising strategy to improve tendon healing.