Role Of Scaffold Internal Structure On In Vivo Vascularization In Porous β-TCP

Revascularization, osteanagenesis, and extre- mities syzygium are three close coherent parts in bone trans- plantation. Revascularization is a initial and basic part in the procedure, having a crucial effecting on modus of steanage- nesis and bone healing. Bone substitutes vascularisation in vivo, besides providing nutrients essential for tissue survival, plays also a crucial role in coordinating the activity of bone cells and their migration for bone remodelling , especially in healing en-block bone defect. Revascularization is a bottleneck to bone tissue engineering ,most of studies are limited by revascularization in big extent because of the shortage of blood in implants that will lead to cell trophopathy.Thus, revascularization of bone implants is a problem that must solved.Recently, various methods have been used in the improvement of the efficiency of bone substitutes vascularisation in vivo, such as combination with vascular endothelial cell(VEC)and vascular endothelial growth factor(VEGF),and microsurgical technique in bone tissue engineering But other studies demonstrated that porous structure which can provoke the fast vascularisation in cancellated bone transplants is a key to bone remodeling though cancellated bone being abundant of cell and osteoinductive factor. Thus like cancellated bone, the porous structure for fast vascularisation in tissue engineering bone scaffold is a important effect factor to bone substitutes transplantation.Searching structural agent and determining optimal texture parameters are very important in find the most suitable scaffold internal structure on in vivo vascularization. But there are seldom study about the role of scaffold internal structure on in vivo vascularization in bone tissue engineering scaffold,and all studies were lack of quantitation result.On the other hand, most of these conclusions were based on studies using implants of random pore geometry and random pores of various sizes with smaller interconnecting,which limited result and leaded to imcompatible conclusions. Thus the objective of our study is searching the best scaffold internal structure on in vivo vascularization and optimal texture parameters. The implants used in the study are wafe-type porousβ-TCP bioceramics contain global pores of near the identical and pore interconnection pathway between all adjacent pores, the density of pore interconnection pathway is 100%. The size of an individual pore can be adjusted precisely according with requirement.This experiment has two parts, the first objective is to study the role of general structure of scaffold and search the structural agent.Two different three-dimensional structureβ-TCP biomaterials(waferβ-TCP , which have regular pore and the higher rate of pore interconnection, and granulationβ- TCP, which is the same with waferβ-TCP in weight ) were implanted separately into fascia lumbodorsalis of every rabbit in order to compare the role of two scaffold internal three dimensional structure of on vascularization ofβ-TCP bio- materials in vivo. The result indicated that vascularization of wafer porousβ-TCP in vivo is better than granulation In four weeks of implantation, the result of histology indicated that the wafer artificial bone had vascularized completely. The number and lumens of blood vessel had increased, and the blood vessel had been mature. To compare with the wafer artificial bone, the vascularization rate of the granulation artificial bone biomaterials is slower in vivo, and the number of blood vessel is less. On the other hand, the smaller lumens diameter and the infaus structure exist in most of blood capillaries. Many blood vessels were not mature in four weeks. We concluded that regular pore and the higher rate of pore interconnection are good to vascularization of scaffold. There are many irregular natural pore between gran- ulationβ-TCP which is stuffed closed, so some pore interconnection pathways are narrow and irregular, even interconnection blind area. These narrow pore interconnection pathways are disadvantageous to blood vessels ingrowth, particularly larger vessels. Blood vessels can't run through several pore and link into vessel web because of interconnection blind area. So the pore and interconnection pathway in scaffolds is a key factor for vascularization.In second study, on the base of result of the first experiment, eight kinds of wafe-type porousβ- tricalcium phosphate (β-TCP) with different pore size and different pore interconnection pathway were obtained through same procedure. Purpose of this study was the analysis of the role of pore size and pore interconnection pathway on in vivo vascularization in porous bioceramic to be used as bone substitutes and search for mechanisms about the role of structure on vascularization,and conclude the specifical texture parameters. Allβ-TCP blocks were implanted into the animal model that is same with the first study. On weeks 1, 2, 4, and 8 after the operation, the implantedβ-TCP blocks were extracted and use the same indicatrix and method with the first study to observe. The histological analysis of specimens at different time after in vivo implantation revealed different vascularization depended on pores and pores interconnection. The vascularisation in the scaffolds with larger pore size and interconnection pathway size was better than in the small pore size and interconnection pathway size. The larger blood vessels were more abundant in large pore size. In the scaffolds with larger interconnection pathway size, a significant amount of blood vessel was observed, as well as the vessels were larger than small interconnection pathway size. The result of RBI supported the conclusion sufficiently. Interestingly enough, the best proportion of not only the number of blood vessels but also vessels diamete were represented in the scaffold (pore sizes is 400～500μm,the size of pore interconnection pathway is 120μm).Here we show that pore size and pore interconnection of scaffolds can influence the pattern of blood vessels invasion. The interconnections appeared to be limiting the number of blood vessels running through adjacent pores. Both the pore size and interconnection pathway could limit the size of blood vessels, interconnection pathway is the portal of blood vessels accessing the pores,pore is seen as the space for the growth of vessel ,the larger pores will support the larger space.Larger interconnection pathway and higher density of interconnection will can make more new blood vessels into web. On the other hand, the composition of pore and interconnection pathway was also a critical and regardful factor of vascularisation in bioceramic, the best composition of two structure factors will promote vascularization. The idea of experiment and variation of scaffolds structure are newer than studies in the past.On the other hand ,the conclusion is newer and more specifical.We conclude that both the pore size and interconnection pathway can affect vascularization of scaffolds and mechanism of two factors affecting the quantity and size of vessels.Moreover, the optimal texture parameters are determined. These conclusions in two studies will support new ideal for the improvement of the efficiency of bioceramic bone substitutes vascularisation in vivo.At the same time, these conclusions will help to choose the optimal structure of bone implants.