Abstract
Fused deposit modeling (FDM) 3D printing technology cannot generate scaffolds with high porosity while maintaining good integrity, anatomical-surface detail, or high surface area-to-volume ratio (S/V). Solvent casting and particulate leaching (SCPL) technique generates scaffolds with high porosity and high S/V. However, it is challenging to generate complex-shaped scaffolds; and solvent, particle and residual water removal are time consuming. Here we report techniques surmounting these problems, successfully generating a highly porous scaffold with the anatomical-shape characteristics of a human femur by polylactic acid polymer (PLA) and PLA-hydroxyapatite (HA) casting and salt leaching. The mold is water soluble and is easily removable. By perfusing with ethanol, water, and dry air sequentially, the solvent, salt, and residual water were removed 20 fold faster than utilizing conventional methods. The porosities are uniform throughout the femoral shaped scaffold generated with PLA or PLA-HA. Both scaffolds demonstrated good biocompatibility with the pre-osteoblasts (MC3T3-E1) fully attaching to the scaffold within 8 h. The cells demonstrated high viability and proliferation throughout the entire time course. The HA-incorporated scaffolds demonstrated significantly higher compressive strength, modulus and osteoinductivity as evidenced by higher levels of alkaline-phosphatase activity and calcium deposition. When 3D printing a 3D model at 95% porosity or above, our technology preserves integrity and surface detail when compared with FDM-generated scaffolds. Our technology can also generate scaffolds with a 31 fold larger S/V than FDM. We have developed a technology that is a versatile tool in creating personalized, patient-specific bone graft scaffolds efficiently with high porosity, good scaffold integrity, high anatomical-shaped surface detail and large S/V.
Highlights
With an annual cost of more than $2.5 billion, diseases and trauma resulting in bone defects have affected 500,000 lives/year in the US and can be classified as a serious health problem [1]
Large surface area-to-volume ratio are always desirable for tissue engineering [23]
As with previous studies that focused on producing “anatomically-shaped scaffolds”, we focused on recapitulating the outer anatomic shape of the bone rather than the internal structure [12,17]
Summary
With an annual cost of more than $2.5 billion, diseases and trauma resulting in bone defects have affected 500,000 lives/year in the US and can be classified as a serious health problem [1]. Teflon cannot be used to generate anatomical shapes and ceramic requires a wax inverse-mold which increases the processing time and risks reducing accuracy They share a common limitation that the mold is difficult to remove after the scaffold is fabricated. We report on our success fabricating anatomically-shaped bone scaffolds using a novel indirect 3D printing and perfusion (3D P&P) technique. This innovative approach utilizes the 3D printing of an anatomically-shaped mold using PVA, casting PLA or PLA-HA mixed salt particles in the organic solvent solution, and perfusion-based methods to rapidly remove solvent, porogen particles, and residual water. CSSaliicmmiuiimllaarrDteotpoothstiehtieoonstoesotdeoifdfeiffreenretinattiiaotnioanctiavcittiyviotbyseorbvseedrvwehdenwuhseinnguAsLinPgasAaLPbioams aarkebri,otmhearpkreer-, tohsetepoSrbimel-aoislstastresothoboltawhsetisnoscshrteeooawsdeiidfnfecarrceetniavtsiieatdytiooancftciavaclitctiyivuiotmyf cdoabelpsceioursvmiteidodnewp(hFoeisgnituiuroesni8n()gFwiAghuLerPne a8cs)ulwatuhbreieondmcwaurilktthueirne, dtbhowethipthrtehin-e obPsoLtetAhobtlhaaenstdsPLshPAoLwAan-iHdncAPreLaAssce-aHdffAaocldtsicsv.aitffyBoooldfthsc.alABcioLutPmh AdaenLpdPosacintaidolcnicua(mFlciiguudmreepd8oe)spiwtoihosneitniocanurelatruebreibodimowmairtakhreiknresrbsootofhf tccheeellll PooLssAtteeooddaiinffffdeerreePnnLttiiAaatt-iiHoonnAwwsiittchhafccfoaallcdciisuu.mmBddoeethppoossAiittLiiooPnn bbaeeniidnngg cmmaloocrriueemssppeedcciiefifpiccotsthhitaaionnnAALLaPPreaaccbttiiivvoiimttyya..rSSkiiemmrsiillaaorrfttoocttehhllee ooosssttteeeooodiinnifddfeuurccettniivvtiiiatttyyiooonff ttwhhieethHHcAAaloocibbussmeerrvvdeeeddpoiinnsitthhioeenaabsssseaainyygoomff AAoLrLePPsaapccettciivvifiiittcyy,,thHHaAAn--AiinnLccoPorrppacootrriaavttieetydd. ssScciaamffffioolallddr sstosshhtoohwwe osssiigtgennoiiififniccdaaunncttltlyiyvhhitiiygghhoeefrrthccaaellccHiiuuAmmoddbesepeproovsseiitdtiiooinnnttthhhaaennattshhseaeyPPLLoAfAA--ooLnnPllyyassccctaiavfffifotoylld,dH((ppA
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