Design and Manufacture of Combinatorial Calcium Phosphate Bone Scaffolds

Abstract

It is well known that pore design is an important determinant of both the quantity and distribution of regenerated bone in artificial bone tissue scaffolds. A requisite feature is that scaffolds must contain pore interconnections on the order of 100-1000 μm (termed macroporosity). Within this range, there is not a definitive optimal interconnection size. Recent results suggest that pore interconnections permeating the scaffold build material on the order of 2-20 μm (termed microporosity) drive bone growth into the macropore space at a faster rate and also provide a new space for bone growth, proliferating throughout the interconnected microporous network. The effects of microstructural features on bone growth has yet to be fully understood. This work presents the manufacture and characterization of novel combinatorial test scaffolds, scaffolds that test multiple microporosity and macroporosity designs within a single scaffold. Scaffolds such as this can efficiently evaluate multiple mechanical designs, with the advantage of having the designs colocated within a single defect site and therefore less susceptible to experimental variation. This paper provides the manufacturing platform, manufacturing control method, and demonstrates the manufacturing capabilities with three representative scaffolds.

Micropore-induced capillarity enhances bone distribution in vivo in biphasic calcium phosphate scaffolds

“…For MP scaffolds, poly(methyl methacrylate) (PMMA) microspheres (Matsumoto Microsphere M-100, Tomen America, New York, NY) with a nominal size of 5 μm (5.96 ± 2.00 μm with a range of 2–14 μm [36]) were added to the ink as sacrificial porogens in equal volume to the HA contained in the slurry; hence the MP scaffolds were nominally 50% microporous. HA ink was loaded in a syringe and a micro-robotic deposition system [37,38] was used to deposit scaffolds, 12 mm in diameter and 8 mm in height, with alternating layers of orthogonal rods. Deposited scaffolds were sintered at 1300 °C for two hours to burn out all of the chemical additives and porogens and to densify the powder.…”

A mechanism for effective cell-seeding in rigid, microporous substrates

“…First, we precisely control porosity on two distinct length scales. We fabricate scaffolds using a robotically controlled, directed deposition, ink extrusion system [7–10], which allows us to control macropore size and geometry directly. We control microporosity in part by incorporating different ink formulations in a single scaffold [7] and/or through the use of PMMA microspheres as sacrificial porogens.…”

Net shape fabrication of calcium phosphate scaffolds with multiple material domains

“…Accurate filament starting and stopping requires an extrusion rate control method that is more sophisticated than the simple static relationship given above. We use machine vision feedback and learning-based control to automatically construct a library of calibration maps that are accessed by the central computer to perform the correct plunger displacement profile for transient flow rate modulation; details on this algorithm can be found in [45] and [68]. The accurate start-stop capability enables two different filaments to abut, thereby seamlessly integrating multiple materials into a single scaffold.…”

“…The two primary scaffold design variables are the scaffold envelope and the location of different material domains. Scaffold macroporosity is the same in all designs as the authors have explored this design space in previous works [45]. Macroporosity designs are nominally Ø=398 μm, H=257 μm, and W=351 μm after sintering (figure 1).…”