Calcium Phosphate Nanoclusters For Hard Tissue Treatment

Biomineralization is an important tactic by which biological organisms produce hierarchically structured minerals with marvellous functions.Biomineralization studies typically focus on the mediation function of organic matrices on inorganic minerals,which helps scientists to design and synthesize bioinspired functional materials.However,the presence of inorganic minerals may also alter the native behaviors of organic matrices and even biological organisms.This thesis discusses the latest achievements relating to biomineralization mechanisms,the manufacturing of biomimetic materials and relevant applications in biological and biomedical fields.The successful modification of biological systems using materials is based on the regulatory effect of inorganic materials on organic organisms,which is another aspect of biomineralization control.This thesis is composed of six chapters:In chapter 1,we learn from nature that organic matrices can regulate inorganic crystallization,including the processes of nucleation,growth,phase transformation,orientation and assembly.To date,scientists have synthesized and biomimetically designed various advanced bioinspired materials with tuneable morphologies,well-organized structures and improved properties based upon the established biomineralization mechanisms.These achievements have great importance in biomedical applications,including collagen mineralization for hard tissue repair.Furthermore,biomineralization not only produces materials but also protects living organisms in nature.Accordingly,biomimetic mineralization represents another tactic that scientists can utilize to generate biological units with functional materials.Biomineralization studies have progressed from organically controlled material crystallization to material-based biological improvements,opening up a new avenue for related research and applications.However,although we have made great progress regarding crystallization mechanisms and their applications,many processes that remain unknown and/or controversial.In chapter 2,the role of organics in regulating the inorganic crystallization is discussed.For example,N-stearoyl-L-glutamic acid(N18-Glu)can switch calcite crystallization from classical ion-by-ion to non-classical particle-by particle pathway.The synergistic effect of poly acrylic acid(PAA)and poly aspartic acid(PASP)can also control the synthesis of the calcium phosphate nanoclusters(CPNCs),which have small size and characterized by transmission electron microscopy(TEM),cryogenic transmission electron microscopy(cryoTEM),scanning electron microscope(SEM),x-ray diffraction(XRD),Fourier-transform infrared spectroscopy(FT-IR),small angle x-ray scattering(SAXS),Energy dispersive spectroscopy(EDS),thermogravimetric and differential thermal analysis(TG/DTA),etc.The results show that the size of the CPNCs is about 1 nm,and the organic-inorganic ratio as well as the hydration level of the CPNCs is similar to that of native rat bone.These findings emphasize the controllable effect of organic additives on inorganic crystallization.In chapter 3,we study the mineralization process of collagen fibrils in bone and human dentin using the CPNCs.The results show that mineralization preferably occurs on/in the collagen fibrils and that HAP is the final mineral product.The fibrillar mineralization of the collagen was demonstrated using three dimensional(3D)super-resolution stochastic optical reconstruction microscopy(STORM).The CPNCs could also be used for dentin collagen mineralization and human dentin regeneration In this chapter,we provide a simple and safe method to collagen and dentin regeneration.In chapter 4,we use the CPNCs for bone regeneration,as an alternative to traditional bone-regeneration materials.The CPNCs have characteristics similar to that of the biological hydrogel-like matrix in that induces bone formation in vivo.The CPNCs can permeate into collagen fibrils to promote intrafibrillar mineralization with apatite,which we think is a key aspect in effective bonding to the existing bone materials and thus in bone healing.Moreover,the CPNCs efficiently fills the defect,shows no adverse effect,and regenerated part displays satisfactory mechanical performance comparable with the natural rat bone.In chapter 5,we develop the CPNCs for osteoporotic bone treatment,which could be injected into the tibial plateau fractures using injection syringe and permeate into the collagen fibrils.Moreover,the repaired osteoporotic bone by the CPNCs display satisfactory mechanical performance comparable with the natural rat bone.The ability of the injectable CPNCs to permeate into osteoporotic bone fractures,allows osteoporotic bone repair without a surgical incision in biomedical practices.The results demonstrate that bioinspired approaches based on an in-depth understanding of biological biomimetic processes provide a new avenue to materials for regenerative medicine.In chapter 6,we emphasize the biomineralization and biomimetic tactics for hard tissue treatment.Our attempts about the discovery and utilization of CPNCs described here provide a promising bioinspired strategy for collagen mineralization,dentin and bone defection regeneration,and osteoporotic bone treatment.However,some unsolved issues also need to suggest in this chapter.