Introduction /               

Tendons transmit force from muscle to bone and are an important connective tissue in the human body. Often the mention of tendon injuries brings a big frown to people's faces: in most people's perception, the first time they probably learnt about tendon injuries was at the 2008 Olympic Games in China, when the Chinese athlete Liu Xiang regrettably retired because of a ruptured Achilles tendon.

 

Figure 1. from tencent.com
 

Numerous clinical studies have shown that natural repair of tendon ruptures takes more than a year and is often difficult to fully restore the original function of the tendon, which inevitably leads to scarring and persistent pain.

Scientists have long searched for an intervention that would be more effective in repairing tendon injuries and shorten the duration of treatment. The relatively conservative approach of immobilising the tendon in a cast and limiting the movement of the orthosis allows for minimal functional recovery in a relatively short period of time. The use of artificial grafts, while providing better results than conservative treatments, comes with considerable risks, such as immune rejection due to allografts and infection and inflammation due to autografts.

The birth and development of regenerative medicine has provided a more ideal and physiological method for tendon injury repair: mesenchymal stem cells are cultured and expanded in vitro and combined with a biodegradable scaffold to form a complex, which is then implanted into the defective area to proliferate, differentiate and secrete factors to achieve the effect of repairing the tissue. After a period of time, the biomaterials will gradually degrade, and complete biological repair will be achieved.

Most of the existing biologic scaffolds require additional fixation, and poor fixation may lead to synovitis, implant rupture, and various complications, in order to achieve better repair results, and to eliminate the occurrence of adverse reactions. There is an urgent need for a biodegradable and structurally sound scaffold that not only possesses good mechanical properties, but also provides the ability to favour MSC cell growth and guide tissue regeneration.

II. Biological scaffolds combined with MSCs for tendon repair

In an article published in Small titled "Co-Electrospun Silk Fibroin and Gelatin Methacryloyl Sheet Seeded with Mesenchymal Stem Cells for Tendon Regeneration," the authors have The authors used a bioscaffold consisting of silk fibroin (SF) combined with methacrylated hydrogel (GelMA) to inoculate mesenchymal stem cells. Silk fibroin provides supportive strength and ductility to the scaffold, while methacrylated hydrogel promotes cell adhesion and growth, and the composite scaffold is easy to adhere to without the need for additional immobilisation, and is capable of controlled biodegradation. The inoculation of mesenchymal stem cells on the composite scaffold greatly improved the efficiency of tendon regeneration.

 

 《Wiley Online Library》

 

The article of this public number, "Focusing on the research on the application of silk protein in medical science and technology to promote the upgrading of Guangxi's mulberry sericulture industry" https://mp.weixin.qq.com/s/Pd-ntyOrFyJrnaxBjXdFpw, describes in detail the structure and physicochemical properties of silk protein.

Silk proteins alone, although high in performance and strength, are not very compatible with cells, so researchers are looking to develop a hybrid scaffold with improved mechanical and biological properties in order to improve the regeneration efficiency of tendons. Methacrylated hydrogel (GelMA) is a photosensitive biohydrogel with excellent biocompatibility and can be rapidly cured under visible or ultraviolet light to form a three-dimensional structure suitable for cell growth with strength, which is widely used in tissue engineering and regenerative medicine. The researchers formed mixtures (SG) of silk protein and methacrylated hydrogel in different ratios and fabricated them into nanofibrous sheets, and then performed structural and tensile tests to obtain the ratio with the best performance (SF:GelMA=7:1). The researchers then inoculated the SG nanofibre sheets with MSCs and performed various cellular adaptation tests as well as tests on the ability of the SG composite scaffolds to improve tendon regeneration in a tendon injury model in mice.

 

Figure 3. from the literature [1]

 

III. Cytocompatibility of SG nanofibre sheets

The researchers inoculated the SG nanofibres with MSCs and determined the cytocompatibility by observing the cell viability and cell proliferation over a period of seven days. The results of the study showed that there was a significant increase in cell viability and cell proliferation at all mixing ratios of the SG material, and the positive effect of the SG7 nanofibre sheets on the cells was maximised at a ratio of 7:1. This result demonstrates that SG materials play a positive role in promoting the growth of MSC.

 

Figure 4. from the literature [1]

 

After obtaining this result, the researchers then proceeded to assess the phenotype of MSC on SG nanofibre sheets by qPCR, as well as the assessment of cell attachment and morphology on SG fibre membranes, and the results of the experiments all indicated that the GelMA component in SG7 nanofibre sheets provides a crucial adhesion site for the growth and spreading process of MSC.MSC can attach and spread well on SG7, and express various factors favourable to tendon growth.

 

In vivo tendon regeneration effect

 

In order to verify the therapeutic effect of SG7 nanofibrous membrane on tendon injury in vivo, the researchers sampled rat Achilles tendon injury models and divided them into six groups for a four-week study. After implantation into the mice, SG7 adhered well to the tendon tissue without additional fixation.

 

Figure 5. from the literature [1]

 

At week 2, both damaged and regenerated tendon tissue was observed in all groups, but in the MSC group (included) there were significantly fewer sites of tendon damage compared to the damage group. Analysed by Masson trichrome staining, fewer sites of tendon loss were observed in the SG7 group and the newly formed tendon fibres were denser and neater.

By week 4, it was observed that the tendons in the damaged group still showed a loose, disorganised structure, whereas the MSC group formed a relatively neat, densely stacked regenerated tendon, and the most obvious effect, analysed by Masson trichrome staining, was observed in the SG7 group, with fewer damaged sites than in the other groups, and even with partially negative results identical to those of the healthy group with undamaged tendons.

This result indicates that SG nanofibres are more effective in promoting the repair of tendon injuries, reducing the number of damaged areas in a shorter period of time, and forming well-aligned and dense tendon tissues and muscle components.

 

Figure 6. from the literature [1]

 

V. Summary

In this study, the researcher conducted in vitro and in vivo analyses of tendon repair ability, and the results showed the excellent tendon repair performance of SG7, which provides a favourable environment for the proliferation of MSCs, induces the secretion of cell growth factors, greatly promotes the healing of tendon injuries, and greatly advances the process of tendon tissue remodelling. However, there is still a long way to go as the practical application effect of this study on human body needs to be verified by a large number of experiments.