| Supercritical CO2 foaming(scCO2 foaming)can be utilized to form porous scaffolds under mild conditions,because polymer plasticization caused by scCO2 could reduce its glass transition temperature and melting temperature.Even though scCO2 foaming has been widely applied in preparation of cellular porous materials,the fabrication of porous tissue engineering scaffolds is still on the run.In this study,poly(lactic-co-glycolic acid)(PLGA)was selected as foaming matrix,and porous scaffolds with controllable pore structure were fabricated by scCO2 foaming.Based on the results,bioactive porous PLGA scaffolds were obtained and the release behavior and release mechanism of different bioactive factors were studied in detail.PLGA scaffolds with open pores were prepared by scCO2 foaming/particle leaching,in which submicron NaCl particles(<1?m)served as porogen.Herein,micropores could be formed after leaching out NaCl particles.In addition,NaCl particles could enhance nucleation behavior during foaming process.PLGA scaffolds with open pores were fabricated at 5%and 20%NaCl addition,and the average pore sizes were 170±44 ?m and 67±25 ?m,respectively.The effect of NaCl particles on nucleation was enhanced by the increase of NaCl addition amount to 50%,while the ability of pore growth was weakened due to increased stiffness of the composites.In other words,more micropores or small pores were formed in this case.Meanwhile,the number of pores formed by leaching out NaCl particles increased,and as a result,average pore size of porous PLGA scaffolds decreased.Moreover,operating pressure and temperature had a dominant effect on porous structure of scaffolds by affacting solubility and diffusion of CO2 in the polymer together with the glass transition temperature and viscosity of the polymer.Scaffolds with open pores could be fabricated by regulating addition amount of porogen and operating parameters in scCO2 foaming.Bi-/multi-modal porous PLGA composite scaffolds were one-step fabricated by scCO2 foaming,in which bioactive hydroxyapatite(HA)was selected as nucleation agent The presence of HA could also improve mechanical property and bioactivity of porous scaffolds.Bimodal porous scaffolds could be prepared by adjusting HA addition amount(5-20%),operating temperature(35-55?)and depressurization rate(as low as 0.1 MPa/min).Pressure showed a significant effect on foaming process.Multimodal porous scaffolds with large pores were fabricated under 9 MPa,while cellular porous structure was formed above 15 MPa.The interconnected porosity of scaffolds ranged from 52.53±2.69%to 83.08±2.42%,while compression modulus ranged from 2.67±0.37 to 18.15±5.16 MPa,which could meet the basic requirement for bone and cartilage tissue.Composite scaffolds with bi-/multi-modal porous structure could be fabricated in one step by this method,when compared with supercritical CO2 foaming/particle-leaching.Bioactive porous PLGA scaffolds could be fabricated by scCO2 foaming.In general,loading of bioactive factors was decisive on the final distribution and release behavior in porous scaffolds.Different loading methods were applied for ibuprofen,dexamethasone and HSA in order to achieve uniform distribution of bioactive factors and sustained release from porous scaffolds in this study.(1)Combining supercritical solution impregnation(SSI)and foaming could allow simultaneously drug-loading and foaming to prepare ibuprofen-loading porous PLGA scaffolds with a loading capacity 3.65±0.67%(w/w).Noteworthily,ibuprofen loaded by SSI could subsequently serve as nucleation agent to enhance nucleation behavior.(2)Dexamethasone-loading PLGA microspheres were prepared by co-dissolving/emulsion-solvent evaporation,in which dexamethasone was distributed uniformly in PLGA matrix.Subsequently,dexamethasone-loading porous PLGA scaffolds were fabricated by scCO2 foaming/particle-leaching.Similar with ibuprofen,dexamethasone also served as nucleation agent to strengthen nucleation behavior.(3)Sustained release could be achieved by encapsulating water soluble albumin into Sephadex G50,followed by mixing and foaming of PLGA.Three kinds of bioactive factor-loading porous scaffolds exhibited different release profiles to lay the foundation of loading and multimodal release of two or more bioactive factors.The release behaviors of ibuprofen and albumin were Fickian diffusion by fitting with Ritger-Peppas equation,while the release behaviors of dexamethasone was non-Fickian diffusion.Dexamethasone and ibuprofen were selected as model drugs to study the release mechanism of drugs from porous PLGA scaffolds.The interactions between polymer and dnigs,polymer and water molecules,as well as drug and water molecules in this temary system were studied in detail.Both ibuprofen loaded by SSI and dexamethasone loaded by co-dissolving/emulsion-solvent evaporation' method were molecularly dispersed in PLGA matrix.The diffusion of drug was largely influenced by free volumes of polymer and the wriggle of polymer chains,in which the wriggle of polymer chains played the key role.When free water or water with relatively weak hydrogen bonds diffused into PLGA matrix,the motion of the polymer chains was enhanced to affect total volume,porous structure and porosity of scaffolds,especially for scaffolds with high density of macaopores.The hydrophilicity of scaffolds could be improved by copolymerization with hydrophilic polymer,and modified PLGA scaffolds still had the ability of maintaining the peaformance.Besides,release behavior of drug from porous scaffolds was affected by the interaction between polymer and water molecules.On one hand,the motion of PLGA groups were enhanced by the wriggle of polymer chains to increase the release amount of drug,when water molecules diffused into PLGA.On the other hand,enhanced group motion would prevent more water molecules diffusing into PLGA,therefore the release amount of drug by dissolution decreased.Furthermore,all of PLGA microspheres,dexamethasone and ibuprofen had negative charge to show electrostatic repulsion in solution.It was verified by the fact that ibuprofen had a faster release rate than dexamethasone from porous scaffolds.Composite scaffolds with bi-/multi-modal porous structure and bioactive scaffolds were successfully fabricated by scCO2 foaming,which took advantage of solvent-free property and mild operating terperature.Release mechanism of drug from porous scaffolds was tentatively elucidated.The results see a promising guide for novel tissue engineering scaffolds design and cells culture in the future. |
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