Novel composite scaffolds based on alginate and Mg‐doped calcium phosphate fillers: Enhanced hydroxyapatite formation under biomimetic conditions

Abstract

In the present study, we synthesized hydroxyapatite (HAP) powders followed by the production of alginate based macroporous scaffolds with the aim to imitate the natural bone structure. HAP powders were synthesized by using a hydrothermal method, and after calcination, dominant phases in the powders, undoped and doped with Mg 2+ were HAP and β-tricalcium phosphate, respectively. Upon mixing with Na-alginate, followed by gelation and freeze-dying, highly macroporous composite scaffolds were obtained with open and connected pores and uniformly dispersed mineral phase as determined by scanning electron microscopy. Mechanical properties of the scaffolds were influenced by the composition of calcium phosphate fillers being improved as Ca 2+ concentration increased while Mg 2+ concentration decreased. HAP formation within all scaffolds was investigated in simulated body fluid (SBF) during 28 days under static conditions while the best candidate (Mg substituted HAP filler, precursor solution with [Ca + Mg]/P molar ratio of 1.52) was investigated under more physiological conditions in a biomimetic perfusion bioreactor. The continuous SBF flow (superficial velocity of 400 μm/s) induced the formation of abundant HAP crystals throughout the scaffolds leading to improved mechanical properties to some extent as compared to the initial scaffolds. These findings indicated potentials of novel biomimetic scaffolds for use in bone tissue engineering. K E Y W O R D Sbiomimetic perfusion bioreactor, bone tissue engineering, macroporous scaffolds, β-tricalcium phosphate | INTRODUCTIONBone tissue is reported to be the second most transplanted tissue after blood due to an increasing number of patients with bone defects due to trauma, tumors, infection, and genetic diseases. 1,2 Bone tissue engineering could be a promising strategy to address the shortage of bone transplants by in vitro regeneration of functional tissue equivalents. In recent years, research in this area is focused on developing biomimetic scaffolds with structural similarity to bone tissue and exhibiting bioactive, biocompatible, osteoconductive, and osteoinductive features, as well as suitable mechanical strength, while being cost-effective and easy to handle. [3][4][5] Bone is a composite material comprised of organic components (mostly collagen type I, fibrin, and noncollagenous matrix proteins) reinforced with inorganic calcium phosphate nanostructured crystals. 6 Therefore, considerable attention has been given to the development of biomimetic composite scaffolds based on polymers with embedded inorganic calcium phosphate materials. [7][8][9] The most frequently