Collagen-Inspired Nano-fibrous Poly(L-lactic acid) Scaffolds for Bone Tissue Engineering Created from Reverse Solid Free
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Collagen-Inspired Nano-fibrous Poly(L-lactic acid) Scaffolds for Bone Tissue Engineering Created from Reverse Solid Freeform Fabrication Victor J. Chen,1 Laura A. Smith,1 and Peter X. Ma1-3 1 Department of Biomedical Engineering, 2Biologic and Materials Sciences, and 3 Macromolecular Science and Engineering Center, University of Michigan. Ann Arbor, MI 48109-1078, U.S.A. ABSTRACT Reverse solid freeform (SFF) fabrication was used to create highly-controlled macroporous structures in nano-fibrous poly (L-lactic acid) (PLLA) scaffolds. By using a computer-aided design (CAD) program to create a negative template for the scaffold, the three-dimensional (3-D) mold was created on a 3-D printer using a wax. After the template was printed, a solution of PLLA in tetrahydrofuran (THF) was cast into the mold, and was subsequently phase separated at -70°C which gives the nano-fibrous morphology. This resulted in a 3-D nano-fibrous scaffold with a uniform fiber mesh throughout the entire matrix, and greatly increased the surface area within the scaffold. Fiber diameters in these scaffolds were 50-500 nm, similar to type I collagen, and the densities of the fiber meshes can be altered by changing the polymer concentration. To examine the scaffold’s potential for tissue regeneration, MC3T3-E1 osteoblasts were seeded and cultured on the scaffolds. Results show that the osteoblasts attached and proliferated on the scaffolds. After 6 weeks in culture, bone-like tissue was evident within the nano-fibrous scaffolds. By having the ability to control the macroporous architecture, interconnectivity, orientation, and external shape of the scaffold, as well as the nanometer-scaled fibrous features in the pore walls, this SFF fabrication/phase separation technique has great potential to design and create ideal scaffolds for bone tissue engineering. INTRODUCTION Tissue engineering is a promising field that strives to create biological alternatives for harvested tissues, implants, and prostheses [1]. One method involves the introduction of cells and/or tissue-inducing factors on a biodegradable scaffold, where the neo-tissue can regenerate and eventually replace the volume of the degrading scaffold. Since most primary organ cells are believed to be anchorage-dependent and require specific environments for growth, the success of tissue engineering relies greatly on the development of suitable scaffold systems for both in vitro tissue culture and subsequent in vivo neo-tissue formation [2]. To accomplish this, scaffolds should possess the following characteristics. First, the scaffold should have an open macroporous network for uniform cell seeding and neo-vascularization, as well as a microporous architecture to maximize mass transport of nutrients and metabolic waste removal throughout the scaffold. Secondly, the scaffold should possess a suitable surface and a high surface area/volume ratio for cell attachment, proliferation, and differentiation. Finally, the scaffold should provide a three-dimensional (3-D) template that has suffici
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