This study analyzed the in vivo performance of composite degradable bone repair products fabricated using the TheriForm process, a solid freeform fabrication (SFF) technique, in a rabbit calvarial defect model at 8 weeks. Scaffolds were composed of polylactic-co-glycolic acid (PLGA) polymer with 20% w/w beta-tricalcium phosphate (beta-TCP) ceramic with engineered macroscopic channels, a controlled porosity gradient, and a controlled pore size for promotion of new bone ingrowth. Scaffolds with engineered macroscopic channels and a porosity gradient had higher percentages of new bone area compared to scaffolds without engineered channels. These scaffolds also had higher percentages of new bone area compared to unfilled control defects, suggesting that scaffold material and design combinations could be tailored to facilitate filling of bony defects. This proof-of-concept study demonstrated that channel size, porosity, and pore size can be controlled and used to influence new bone formation and calvarial defect healing.

Tight control of pore architecture in porous scaffolds for bone repair is critical for a fully elucidated tissue response. Solid freeform fabrication (SFF) enables construction of scaffolds with tightly controlled pore architecture. Four types of porous scaffolds were constructed using SFF and evaluated in an 8-mm rabbit trephine defect at 8 and 16 weeks (n = 6): a lactide/glycolide (50:50) copolymer scaffold with 20% w/w tri-calcium phosphate and random porous architecture (Group 1); another identical design made from poly(desaminotyrosyl-tyrosine ethyl ester carbonate) [poly(DTE carbonate)], a tyrosine-derived pseudo-polyamino acid (Group 2); and two poly(DTE carbonate) scaffolds containing 500 microm pores separated by 500-microm thick walls, one type with solid walls (Group 3), and one type with microporous walls (Group 4). A commercially available coralline scaffold (Interpore) with a 486-microm average pore size and empty defects were used as controls. There was no significant difference in the overall amount of bone ingrowth in any of the devices, as found by radiographic analysis, but patterns of bone formation matched the morphology of the scaffold. These results suggest that controlled scaffold architecture can be superimposed on biomaterial composition to design and construct scaffolds with improved fill time.

The current study analyzes the in vivo performance of porous sintered hydroxyapatite (HA) bone repair scaffolds fabricated using the TheriForm solid freeform fabrication process. Porous HA scaffolds with engineered macroscopic channels had a significantly higher percentage of new bone area compared with porous HA scaffolds without channels in a rabbit calvarial defect model at an 8-week time point. An unexpected finding was the unusually large amount of new bone within the base material structure, which contained pores less than 20 microm in size. Compared with composite scaffolds of 80% polylactic-co-glycolic acid and 20% beta-tricalcium phosphate with the same macroscopic architecture as evaluated in a previous study, the porous HA scaffolds with channels had a significantly higher percentage of new bone area. Therefore, the current study indicates that scaffold geometry, as determined by the fabrication process, can enhance the ability of a ceramic material to accelerate healing of calvarial defects.

Intraosseous transcutaneous amputation prostheses may be able to overcome the problems that stem from the nonuniform distribution of pressure seen in the conventional stump-socket prosthetic replacement devices. Transcutaneous devices have had limited success in amputees. By optimizing the attachment of the skin to the prosthetic, intraosseous transcutaneous amputation prostheses may become clinically viable options. This report details studies evaluating the development of a modified titanium construct with a specially machined surface to increase the adherence of tissue as well as scaffold. A computer-aided biology tool was used to fabricate polycaprolactone (PCL) scaffolds with a specific three-dimensional architecture. To extrude the PCL, it was dissolved in acetic acid to produce a 70% PCL liquid. A scaffold with a porosity of >50% was fabricated to have a tensile strength similar to skin. The presence of a specially machined surface greatly increased the adhesion of the PCL scaffold to the titanium constructs. When the 70% PCL was properly neutralized by heating at 55 degrees C and washing in 90% ethanol (EtOH), there was only a decrease (10%) in the viability of cells seeded onto the PCL constructs when compared with the cells in culture. The antibacterial properties of titanium dioxide anatase, silver nanoparticles, and chlorhexidine diacetate mixed in either type I collagen or hyaluronic acid (HA) were assessed. The addition of 1% (w/w) chlorhexidine diacetate in HA resulted in a 71% decrease in bacteria seen in nontreated HA. These results show promise in developing a novel engineered titanium and PCL construct that promotes effective adhesion between the titanium-skin interface.

Numerous solid freeform fabrication (SFF) or rapid prototyping (RP) techniques have been employed in the field of tissue engineering to fabricate specially organized three-dimensional (3-D) structures such as scaffolds. Some such technologies include, but are not limited to, laminated object manufacturing (LOM), three-dimensional printing (3-DP) or ink-jet printing, selective laser sintering (SLS), and fused deposition modeling (FDM). These techniques are capable of rapidly producing highly complex 3-D scaffolds or other biomedical structures with the aid of a computer-aided design (CAD) system. However, they suffer from lack of consistency and repeatability, since most of these processes are not fully controlled and cannot reproduce the previous work with accuracy. Also, these techniques (excluding FDM) are not truly direct-print processes. Certain material removing steps are involved, which in turn increases the complexity and the cost of fabrication. The FDM process has good repeatability; however, the materials that can be used are limited due to the high temperature needed to melt the feedstock. Some researchers also reported that the scaffolds fabricated by FDM lack consistency in the z-direction. In this paper, we will present a true direct-print technology for repeatedly producing scaffolds and other biomedical structures for tissue engineering with the aid of our Computer Aided Biological (CAB) tool. Unlike other SFF techniques mentioned above, our direct-print process fabricates scaffolds or other complex 3-D structures by extruding (dispensing) a liquid material onto the substrate with a prescribed pattern generated by a CAD program. This can be a layer-by-layer 2.5 dimension build or a true 3-D build. The dispensed liquid material then polymerizes or solidifies, to form a solid structure. The flexibility in the types of materials that can be extruded ranges from polymers to living cells, encapsulated in the proper material. True 3-D structures are now possible on a wide range of substrates, including even in vivo. Some of the advantages of the process are a) researchers have full control over the patterns to be created; b) it is a true direct-print process with no material removing steps involved; c) it is highly consistent and repeatable; and d) it is highly efficient and cost-effective. This paper will first give a detailed description of the CAB tool. Then, it will present a detailed process for printing polycaprolactone (PCL) into a defined 3-D architecture, where the primary focus for these constructs is for use in tissue engineering applications. Finally, mechanical characterization results of the printed scaffolds will be included in the paper.