| The research of growth factors has been active since nerve growth factor and epidermal growth factor were found in 1950. The function of growth factor in the healing process of the bone and soft tissue was extensively studied. But, little was known about the specific growth factors which might contribute to flexor tendon healing.Up to the present, the specific tendon growth factor has not been found. At present, the definition of growth factor used extensively is:growth factor is composed and secreted by varieties of cells, with low molecular weigh protein, proteoglycan or multiple peptides protein. By combining with the specific receptors of the aim target, it modulates the varieties of biological behaviours of cells, such as cell proliferation, differentiation and migration etc. The important growth factors include seven categories as follows: (1) epidermal growth factor (EGF):transfer growth factor (TGF) was within the category; (2) nerve growth factor(NGF); (3) fibroblast growth factor(FGF); (4) platelet-derived growth factor(PDGF); (5) insulin-like growth factor(IGF); (6) hemapoietic cell growth factor:such as Epo,CSF; (7) interlukin growth factor. Growth factors possess multiple resources characteristics. In unwound tendon, both tenocytes and tendon sheath cells can synthesize partial growth factors; After tendon wounded, local inflammatory cells, such as macrophage can arrive at the injury site by blood circulation, and release the growth factor like platelet. These growth factors act by autosecretion and parasecretion forms. With the development of the molecular biological technique, multiple growth factors have been found in tendon. Up to the present, more definitely existing growth factors include bFGF, IGF, TGF- β ,PDGF, and EGF etc. In the wound healing process, growth factors first are released and activated during the inflammatory stage, and further act in the process of angiogenesis, cell recruitment and proliferation, deposition of extracellar matrix and remodelling.There are several growth factors in the wound tendon healing process. At present, growth factors often studied are IGF, bFGF, and TGF- 0 etc. As a kind of multiple peptides, IGF-1 shares multiple physiological functions in vivo. It has been demonstrated that it could promote the mitosis of the glomerulose mesangial cell line, fibroblast line and osteoblast line. In recent years, the function of IGF-1 in the tendon healing has been noted day by day. IGF-1 has distinct function of promoting tenocytes proliferation, and in a dose dependent in some extent. IGF-1 effects the cell cycle by promoting substance synthesis concerning cell mitosis, thus accelerating the process of the cell mitosis, shortening the tenocyte cycle and promoting tenocyte development. Pietrzkowski etc. studied the inhibition of cellular proliferation by peptide analogues of insulin-like growth factor. These analogues were able to inhibit the autohosphorylation of the IGF-1 receptor as well as the growth of several different cell types. Consequently, these analogues seem to show great potential both as probes of the structure/function, activities of the IGF-1 signalling pathway and as novel clinical strategies in controlling abnormal cellular growth.In recent years, concerning bFGF molecular level study of promoting tendon healing mechanism has been hot topic. Chang studied the New Zealand white rabbit forepaws in a zone II flexor tendon wound-healing model by in situ hybridization and immunohistochemistry technique. Chang found that both normal tenocytes and tendon sheath cells could produce bFGF, and bFGF mRNA expression increased in tenocytes, tendon sheath cells and inflammatory cells after injury. The function of promoting wound healing of bFGF was related with promoting cell proliferation and cellular matrix synthesis. bFGF promoted tendon healing by promoting cell proliferation response, rather than by chemotaxis. XuYan's research showed that bFGF could distinguishly stimulate DNA and type I collagen synthesis in tenocytes, and increasedNF- k B instant transcript gene expression. Therefore, when designing and using the experiment of growth factor to promote tenocyte growth, it is very likely that promoting growth substances could arrive at aim by one kind of growth factor or mainly by one kind of growth factor. Direct modulation of the NF- k B factor expression level, or extracorporeal addition of NF- k B factor could cause the same results as multiple growth factors. So it cound modulate tenocytes growth and proliferation in genetic transcriptive level.Their isoforms of human transforming growth factor beta family exist—TGF- ft1, TGF- ft 2, and TGF- ft 3. TGF- ft is found to stimulate, inhibit, or stimulate and inhibit in cell differentiation, immune system, cell proliferation and inflammatory response to some degree. It is a chemical inducer ^specially to the extracellular matrix synthesis and remodelling. TGF- ft 1 is a cytokine with numerous biologic activities related to wound healing and pathologic excessive scar formation. During the operation week, modulation of the TGF- ft 1 amount would help decrease tendon adhesion formation. TGF- ft 1 plays an important role in both intrinsic and extrinsic mechanisms of tendon wound healing. There is great intrest in inhibitors of transforming growth factor beta, including neuralizing antibody and proteoglycans such as decorin. By using these agents to modulate the deleterious effects of transforming growth factor beta-1, surgeons might be able to manipulate flexor tendons to heal with minimal adhesions, thus allowing improved postoperative range of motion and hand function. Wang Zhengguo found that the modulation of TGF family ratio, such as upregulation the level of TGF- ft 3 higher than TGF- ft 1/TGF- ft2, could benefit to limit scar formation.Of course, there are many agents of modulating tendon healing in vivo. Growth factors like IGF, bFGF and TGF- ft etc. are in the correlated network of multiple growth factors. They interact each other, and increase their biological effects. So the genuine function of one factor will be studied in the future. About tendon, there are only IGF, bFGF, TGF etc. several factors been discussed in tendon repairing. Up to the present, it hasn't been definite whether exists the specific tendon growth factor. A lot of growth factors which have been found are low molecular weight protein withlow secretion. Cui Zhiming etc. found that 45kDa protein secretion in the extract from healing tendons increased in the early injury stage, and could promote proliferation of tenocytes growth, thus concluding that this protein might be a kind of specific tendon growth factor.Adhesion happens inevitably after tendon injury or transplant. It is an emergency problem to be resolved. In recent years, with the development of molecular biology research and genetic engineering technique, some scholars began taking advantage of growth factors to modulate the proliferation of tenocytes, further to study promoting wound tendon healing, prevention of adhesion, and artificial tendon by tissue engineering etc. Up to date, there hasn't been an optimal growth factor of promoting tendon healing. In the future, on one hand, we'll choose specific promotion factors of tendon healing from these factors been found, and investigate the mechanisms of these factors to promote tendon healing; on the other hand, we'll look for novel factors from aim targets. Especially, people are confident to extract an optimal factor of promoting tendon healing from the wound-healing flexor tendon. An optimal growth factor would be found, purified and applied to clinical practice soon. Summary1. There are several growth factors in the wound tendon healing process. At present, growth factors often studied are IGF, bFGF and TGF- P etc.2. IGF-1 has distinct function of promoting tenocytes proliferation, and in a dose dependent in some extent.3. The function of promoting wound healing of bFGF is related with promoting cell proliferation and cellular matrix synthesis. bFGF promotes tendon healing by promoting cell proliferation response, rather than by chemotaxis.4. TGF- P i plays an important role in both intrinsic and extrinsic mechanisms of tendon wound healing. TGF- $ i is a cytokine with numerous biologic activities related to wound healing and pathologic excessive scar formation.5. The peptide analogues of IGF and the inhibitors of TGF- ￡ can inhibit the cellular proliferation.6. Experiments reveal that 45kDa protein might be a kind of specific tendon growthfactor.By using these research, a kind of new idea and a kind of new method are provided. It provides a definite theoretical base to solve the problem of wound tendon postoperative adhension. By modulating these agents, surgeons might be able to manipulate flexor tendons to heal with minimal adhensions, thus allowing improved postoperative range of motion and hand function.We believe that an optimal growth factor would be found, purified and applied to clinical practice soon.
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