Porous Scaffolds Fabricated By Phase-stabilized Foaming And Their Applications In Controlled Release And Tissue Engineering

Porous biomaterials are of great importance and have been extensively applied in the biomedical fields,such as tissue engineering scaffolds,carriers for drug and cell delivery,biosensors.To date,there are many fabrication strategies of porous biomaterials including freeze-drying,template method,foaming and electrospinning techniques.These preparation techniques,however,cannot readily control pore structure and material components at the same time in a green,economic and fast fabrication process.Recently,as an emerging fabrication strategy to prepare porous biomaterials,3D printing can satisfy the aforementioned criterion yet it is time consuming and costly,largely limiting its applications.In this work,a novel starch-assisted foaming approach based on the gelatinization and retrogradation properties of starch to fabricate porous materials was developed.Different porous ceramics and ceramic/bioglass?BG?composite foam scaffolds were prepared by this phase-stabilized foaming strategy.The properties of these materials were evaluated,and their potential applications in controlled release and tissue engineering were also explored.In the first part of this study,different ceramic powders were mixed with starch suspension and different ceramic-based porous foams were prepared by the phase-stabilized foaming approach.In addition,porous alumina?Al₂O₃?and hydroxyapatite?HA?ceramics were fabricated by sintering such ceramic-based porous foams.The properties of foams and porous ceramics were tested by apparent density and porosity calculation,scanning electron microscopy?SEM?characterization and mechanical testing.The results indicated that both porous foams and porous ceramics had high porosities of>80%,and consisted of interconnected macro-pores with diameters of400-600?m.Moreover,the compressive strength of the porous foams increased firstly and then decreased when increasing the solid contents of slurry.In addition,ceramic foams with gradient pore size distributions were prepared by setting a temperature gradient,and ceramic foams with multi-layers each of which had different pore size or material components were also fabricated by a casting strategy.For drug or cell delivery applications,HA/starch foams in situ loaded with model drugs?bromophenol blue?BPB?and bovine serum albumin?BSA??or cells were prepared,respectively.The drug-loaded foams have moisture-dependent mechanical properties,and samples with relatively high moisture content exhibit excellent resilience of>98%.Mechano-active and precise release of drug molecules and cells triggered by compressions was achieved in the HA/starch foam.The results showed that the release of BPB exhibited AND logic with dual gates of moisture content?>40%?and compressive strain?>3%?.Meanwhile,this study also confirmed that mechano-active release of BPB,BSA and cells based on the foams had a high release precision of 70 ng,150 ng and 1400 cells per 1cm³sample per compression cycle.For soft tissue engineering application,micro-tissue foams constructed by osteoblasts?MC3T3?,fibroblasts?NIH3T3?and vascular endothelial cells?HUVEC?were fabricated by the phase-stabilized foaming technique,respectively.The results indicated that cells loaded in the micro-tissue foams showed high viability of>95%.Moreover,controlled release of cells was achieved by adjusting the degradation rate of micro-tissue foams by altering the fetal bovine serum?FBS?concentration of cell culture medium.For hard tissue engineering application,HA/bioglass?BG?and Si₃N₄/BG composite scaffolds were prepared by the phase-stabilized foaming technique and sintering.The SEM results showed that these two types of scaffolds all consisted of interconnected macropores with the diameters of 400-600?m.Although these scaffolds had high porosities of 70-80%,both HA/BG and Si₃N₄/BG porous scaffolds all exhibited relatively high compressive strengths of 6.0±1.4 MPa and 19.7±3.1 MPa,respectively.In vitro experiment indicated that these two types of scaffolds all had good biocompatibility,and the in vivo evaluation further confirmed that HA/BG scaffold had good osteoconductivity and induced bone ingrowth to the scaffold.