桃子汉化组移植游戏大全

首页  学术通知  详情

桃子汉化组移植游戏大全:学术讲座|磷酸钙陶瓷中组织形成的物理控制

日期:2023-06-29

报告题目:

磷酸钙陶瓷中组织形成的物理控制

报告时间:

2023年6月30日上午9:30

报告地点:

大学城校区 B12-318会议室



报告人个人简介


Dr. Huipin Yuan is a senior material scientist in Kuros Biosciences BV (The Netherlands). He got his BSc in 1989/his MSc in 1992 from Peking University (Beijing, China) and his Ph.D in 2001 from Leiden University (Leiden, The Netherlands). He is a co-founder of Kuros Biosciences BV (The Netherlands) and Scinus Cell Expansion BV (The Netherlands), the owner of Huipin Yuan’s Lab (Sichuan, China) and the founder of Chengdu Aorigin Science and Technology Lt.D (Chengdu, China). Majored in biological science, he optimizes biomaterials according to biological requirements for tissue regeneration. By doing so, he identified surface topography as a key material factor to initiate material-induced bone formation and made two novel synthetic bone grafting materials (AttraX and MagnetOs) available on market for bone regeneration. He clarified osteoclastogenesis as a driving force for material-induced bone formation and thus demonstrated a possibility to improve tissue regeneration by modulating immune responses. He is now working on biological functions of physical cues and novel approaches for tissue regeneration and disease control. He got more than 100 publications (in Advanced Science,  PNAS, Advanced materials, Biomaterials and Acta Biomaterialia) and his work was well accepted with a citation of more than 10,000.


报告摘要

Physical controls of tissue formation in calcium phosphate ceramics

 

Huipin Yuan

 Kuros Biosciences BV, Bilthoven, Netherlands (huipin.yuan@kurosbio.com)

 

   Being chemically similar to the main inorganic components of bone, calcium phosphate ceramics (CaPs) are biocompatible. Meanwhile, the easy formation of bone-like apatite layer on their surface makes CaPs bioactive, allowing a chemical bonding to the newly formed bone. Moreover, the resorption rates of CaPs could be adjusted by the ratio of hydroxyapatite to tricalcium phosphate and cell (e.g. osteoclasts)-mediated resorption guarantees a creeping substitution of the resorbed CaPs with newly formed bone. Furthermore, porous structures similar to those of cancellous bone could be generated in CaPs to facilitate conductive bone ingrowth from the host bone. More interestingly, having specific physicochemical properties, CaPs  can be osteoinductive and give rise to bone formation in non-osseous sites, being capable to  repair large bone defects (e.g. critical-sized bone defects) without additional growth factors and/or osteogenic cells. In short, the discovery of CaPs so far has shed a light on developing ideal bone grafting materials which could replace autologous bone (the gold standard bone substitute) in clinics for bone regeneration.

   Among the physicochemical properties governing material-induced bone formation in CaPs, the surface microstructure appeared to be the key material factor. The presence of micropores (strut pores) in CaPs (in other words, microporosity) was firstly found to be essential for material-induced bone formation to occur, and the critical roles of the dimension of surface microstructure (or surface topography) in material-induced bone formation was identified later on, with the loss of the ability to induce bone formation once the strut pores and the crystal grains are bigger than 1.5?m [as verified with osteoinductive TCP-S (a tricalcium phosphate ceramic with strut pores and crystal grains smaller than 1.0?m) and non-osteoinductive TCP-B(a tricalcium phosphate with strut pores and crystal grains larger than 1.5?m) ].

Chemical cues of calcium phosphate ceramic implants [protein adsorption (e.g. adsorption of growth factors such as bone morphogenetic proteins), ion release (e.g. calcium and phosphate release) and bone-like apatite layer formation] are employed to explain how physicochemical properties of CaPs play their roles in material-induced bone formation. The chemical theory explained well the different tissue responses between TCP-S and TCP-B (bone or no bone formation following an intramuscular implantation). With similar microporosity, TCP-S has a larger surface area to concentrate more proteins (including growth factors), to release more calcium ion and phosphate ion and to facilitate bone-like apatite layer formation than TCP-B. However, material-induced bone formation in AlO ceramic implants with strut pores and crystal grains smaller than 1.5?m (following intramuscular implantation) is obviously against the chemical theory. AlO ceramic did hardly adsorb rhBMP-2 in a cell culture medium containing serum proteins with extra rhBMP-2, AlO ceramic inhibited surface mineralization of containers instead of getting surface mineralization on its own in vitro, Ca and P in AlO in vivo implants were not detected before mineralized bone was observed and of course there is no release of calcium and phosphate from AlO ceramics.

   It is likely that surface microstructure of CaPs instructs material-induced bone formation via physical cues generated therein. The biological functions of physical cues have indeed been shown in the cases of surface pattern-guided mesenchymal cell differentiation, while instead of the responses of mesenchymal stem cells, responses of cells in  innate immune system to surface microstructures including macrophage polarization to M2 and fusion of M2 macrophages to osteoclasts are the key cellular events in material-induced bone formation, with osteoclastogenesis being the driving force for material-induced bone formation. As such, the ability of monocytes to form osteoclasts in vitro could predicate material-induced bone formation in vivo in individuals (and as such, animal dependence of material-induced bone formation were seen). How cells in innate immune system respond to physical cues generated by surface microstructure is not known as yet, while surface microstructure-dependent cell morphology regulating mechanosensitive ion channels (e.g. piezo 1) would be a possible mechanism.

   With macrophage polarization to M2 and fusion of M2 macrophages to osteoclasts being the key cellular events in material-induced bone formation, anything affecting macrophage polarization and osteoclastogenesis has influences on material-induced bone formation. As a result, chemicals enhancing macrophage polarization to M2 and osteoclastogenesis enhanced material-induced bone formation and could make material-induced bone formation possible in non-osteoinductive TCP-B implants. Via macrophage polarization and osteoclastogenesis, hypoxia plays its roles in material-induced bone formation. As such, macrostructure of CaPs has influences on material-induced bone formation. Macropores (with the size of hundreds micron) and concave surface which creates local hypoxia in implants favored material-induced bone formation in CaPs, and because of the more hypoxic status could be reached, ìmplants composed of 212-300?m osteoinductive calcium phosphate ceramic particles enhanced largely material-induced bone formation as compared to their counterparts of 1-2mm (20% bone in available space vs 1% after a 6-week intramuscular implantation).

   Although lots of questions remained un-answered, the identification of the roles of physical cues and the functions of the innate immune system  in tissue formation shed a light on novel approaches for tissue regeneration and disease control.



桃子汉化组移植游戏大全最新网页版在线平台(2025已更新)