On The Model Of Angiogenesis And Growth Of New Tissues

Angiogenesis is an essential biological behavior for the growth of new tissues.Under normal conditions,the new tissues are self-controllable and tissue vascularization can also follow a specific growth law spontaneously to complete the process that is from genesis to development and then to a stable state.But the vascularization and growth of a pathological tissue must be guided by medical intervention toward a direction favorable to health,including to inhibit excessive vascularization and to promote insufficient vascularization properly.In this study,the relationship between angiogenesis patterns and tissue growth in two typical regenerative tissues of tumor and dermal wound has been investigated.In order to explore the mechanisms of angiogenesis and the effects of various patterns of angiogenesis on the growth of regenerative tissues in each stage,we try to find and ascertain the similarities and differences between physiological and pathological angiogenesis.This study included three aspects as follows:(1)To explore the roles of oxygen supply and the endothelial progenitor cells in capillary network constructionEstablishing polygon models for two-dimensional capillary network,we analyzed the oxygen distribution of their network units in normoxic and hypoxic states.The results showed that the hexagon model is most reasonable structure for a uniform two-dimensional(or quasi-two-dimensional)tissue either in a stable state or a development state.This result confirmed by the images of a related literature.Establishing a chemotactic migration model of vascular endothelial/endothelial progenitor cells,we simulated the migration paths of the tip endothelial cells and endothelial progenitor cells which respond to angiogenic growth factors.By the statistical analysis of the simulation results,it was considered that vascular endothelial progenitor cells play a role assisting anastomosis of the vascular sprouts during the construction of new vascular loops.(2)To explore the effects of tumor angiogenesis on tumor growthAn autonomous growth model of layered solid tumor and a mathematical model of tumor vascularization process have been proposed.Based on the proliferative activity of tumor cells depend on oxygen supply and other microenvironment factors the growth model is constructed,which follows the law of autonomous growth of tumor cells under the microenvironment conditions.In the mathematical model of tumor vascularization process,the new blood vessels are formed from three types of angiogenesis pattern that are the angiogenesis in situ,the sprouting and the vasculogenesis from endothelial progenitor cells.The simulation results of two models showed that the ability of angiogenesis affects directly the tumor growth rate.In contrast,the angiogenesis in situ plays a main role in tumor growth and metastasis.(3)To explore angiogenesis mechanisms of skin regeneration induced by usingbiological materials in the wound-healing processA mathematical model of vascularization process in skin regeneration has been proposed.In the model the factors including the variation in the concentration of angiogenic factors,the chenges of capillary density and the formation of microvessels were considered.The source of the new blood vessels in the regenerative tissue has also been described as above three types of angiogenesis.The vascularization of the material undergoes a process in which the quantity of blood vessels changes from nothing to something,reaches the maximum,and then decreases.The three types of angiogenesis play different role in the process.Such as because of endothelial progenitor cells being mobilized,the vascularization of an avascular area is triggered;the sprouting angiogenesis promotes vascularization developing toward avascular area;the angiogenesis in situ increases the density of blood vessels in the material.An animal model of skin wound repair with three control groups in rat was established.While porous films of SF(silk fibroin)and PVA(polyvinyl alcohol)were implanted into a same wound bed in rat dorsal skin,a blank area was set as control group to analyze the vascularization during the regenerative process of dermal tissue induced by biological materials.By H.E staining and immunohistochemical staining of CD34,VEGF,CD 133,and Flt-1,the time evolutions of the distribution of new blood vessels,and the expression level of VEGF of histiocytes,and the representation of endothelial progenitor cells and hematopoietic stem cells participating in formation of new blood vessels were identified.We verified the correlation between the levels of VEGF and the strength of the inflammatory response,and the facts of the endothelial progenitor cells assisting the formation of vascular sprouts,and both the endothelial progenitor cells and the hematopoietic stem cells differentiating into parietal cells and contributing to the maturation of naive blood vessels.In addition,both the SEM and TEM images of appearance characteristics of new blood vessels and their ultrastructure provided convincing evidences to help to understand the mechanisms of angiogenesisThe experimental results have shown that the biodegradable SF was completely degraded on day 60 after surgery,and was substituted by the new tissues.Most of the area in the wound was transformed into normal dermal tissue.It is showed that wound healed well,the scar was less,and the skin appendage regeneration was observed in the scarless area.These studies suggest that the silk fibroin materials as a scaffold for skin regeneration have good prospects.