title: Rapid prototyping amphiphilic polymer/hydroxyapatite composite scaffolds with hydration-induced self-fixation behavior.
abstract: Two major factors hampering the broad use of rapid prototyped biomaterials for tissue engineering applications are the requirement for custom-designed or expensive research-grade three-dimensional (3D) printers and the limited selection of suitable thermoplastic biomaterials exhibiting physical characteristics desired for facile surgical handling and biological properties encouraging tissue integration. Properly designed thermoplastic biodegradable amphiphilic polymers can exhibit hydration-dependent hydrophilicity changes and stiffening behavior, which may be exploited to facilitate the surgical delivery/self-fixation of the scaffold within a physiological tissue environment. Compared to conventional hydrophobic polyesters, they also present significant advantages in blending with hydrophilic osteoconductive minerals with improved interfacial adhesion for bone tissue engineering applications. Here, we demonstrated the excellent blending of biodegradable, amphiphilic poly(D,L-lactic acid)-poly(ethylene glycol)-poly(D,L-lactic acid) (PLA-PEG-PLA) (PELA) triblock co-polymer with hydroxyapatite (HA) and the fabrication of high-quality rapid prototyped 3D macroporous composite scaffolds using an unmodified consumer-grade 3D printer. The rapid prototyped HA-PELA composite scaffolds and the PELA control (without HA) swelled (66% and 44% volume increases, respectively) and stiffened (1.38-fold and 4-fold increases in compressive modulus, respectively) in water. To test the hypothesis that the hydration-induced physical changes can translate into self-fixation properties of the scaffolds within a confined defect, a straightforward in vitro pull-out test was designed to quantify the peak force required to dislodge these scaffolds from a simulated cylindrical defect at dry versus wet states. Consistent with our hypothesis, the peak fixation force measured for the PELA and HA-PELA scaffolds increased 6-fold and 15-fold upon hydration, respectively. Furthermore, we showed that the low-fouling 3D PELA inhibited the attachment of NIH3T3 fibroblasts or bone marrow stromal cells while the HA-PELA readily supported cellular attachment and osteogenic differentiation. Finally, we demonstrated the feasibility of rapid prototyping biphasic PELA/HA-PELA scaffolds for potential guided bone regeneration where an osteoconductive scaffold interior encouraging osteointegration and a nonadhesive surface discouraging fibrous tissue encapsulation is desired. This work demonstrated that by combining facile and readily translatable rapid prototyping approaches with unique biomaterial designs, biodegradable composite scaffolds with well-controlled macroporosities, spatially defined biological microenvironment, and useful handling characteristics can be developed.
authors.affiliation: 1 Department of Orthopedics & Physical Rehabilitation, University of Massachusetts Medical School , Worcester, Massachusetts.
authors.forename: Artem B
authors.initials: AB
authors.lastname: Kutikov
authors.forename: Anvesh
authors.initials: A
authors.lastname: Gurijala
authors.forename: Jie
authors.initials: J
authors.lastname: Song
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D019245:Compressive Strength / Q000187:drug effects; D017076:Computer-Aided Design; D017886:Durapatite / Q000494:pharmacology*; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000187:drug effects; D051379:Mice; D008970:Molecular Weight; D041681:NIH 3T3 Cells; D010012:Osteogenesis / Q000187:drug effects; D011091:Polyesters / Q000494:pharmacology*; D011092:Polyethylene Glycols / Q000494:pharmacology*; D051381:Rats; D013501:Surface-Active Agents / Q000494:pharmacology*; D054457:Tissue Scaffolds / Q000737:chemistry*; D014867:Water / Q000737:chemistry*
chemical_list: D011091:Polyesters; D013501:Surface-Active Agents; C507889:polylactide-polyethylene glycol-polylactide; D014867:Water; D011092:Polyethylene Glycols; D017886:Durapatite