Fabrication And Properties Of Functional Calcium Phosphate/Alginate Microspheres

Calcium phosphate, its composition is similar to inorganic component of bone matrix,having a good binding to bone tissue, and can be widely used in joint spinal fusion, limb trauma,oral and maxillofacial surgery and periodontal defect. During clinical treatment, regularly spherical particles with good flowability are easy to fill, which can form a micron level void structure to lead to tissue ingrowth. Calcium phosphate microspheres used in bone tissue repair field are in a size of diameter between 0.25 mm and 2.0mm according to the size of bone defect in different parts of body. A way to adjust the size of calcium phosphate microspheres need to develop. Bioactive molecules, such as protein, play an important role in bone tissue repairing,but bioactive macromolecules can only exist in vivo for a short time. The processing of protein carrier preparation currently is involved to organic solvents or harsh conditions in the process of preparation. This study focused on the calcium phosphate microsphere for bone repairing. Two parts were developed in the study. The first part was to investigate a method to adjust the size of calcium phosphate microsphere by the electrostatic droplet method under a mild and green condition; and an in vivo study of calcium phosphate composite microsphere was carried out.The second part is to preparation and characterization of calcium phosphate composite microspheres for protein carrier.β-TCP/ALG microspheres were fabricated by the electrostatic droplet method due to the chemical cross-linking of ALG-Ca. The diameters of the microspheres can be adjusted from0.23 mm to 1.72 mm by controlling the process parameters. Based on the orthogonal experiment analysis, the effect on the microspheres particle size in a descending manner is load voltage >mass concentration of β-TCP > mass concentration of ALG-Na >feeding rate. XRD patterns results revealed that β-TCP is the principal phase in the composite microspheres. An in vivo evaluation of the application of composite microspheres for bone repairing was developed in a model of calvaria critical size defect of rats. Micro- CT and histological analysis showed that the composite microspheres promoted bone repairing in some degree, altogether with a fast degradation.An evaluation of the encapsulation efficiency(EE) and drug loading rate(DL) withdifferent sizes of β-TCP/alginate microspheres was carried out when bovine serum albumin(BSA) worked as the model drug. With the decrease of the microspheres particle size, DL and EE were markedly reduced. The addition of hydroxyapatite(HA) can improve the DL and EE,but the burst- release still existed. The composite microspheres with chitosan(CS) coating can make drug sustain-release for 30 days.In this study, a combined processing method of the high voltage electrostatic droplet method with chemical cross-linking was applied to fabricated calcium phosphate composite microspheres for bone repairing. The processing is a simple step under mild conditions without organic solvents, other toxic and harmful substances. Using the method, we could effectively control the size of calcium phosphate composite microspheres, further design to load and control-release the bioactive substances. The study not only promotes the application of calcium phosphate microspheres in bone repairing, but can widen its application scope in the domain of biological medicine.