B. Holmes, C-Y Kuo, N. Arumugasaamy, N. Gandhi, C. Rossi, J.P. Fisher, L. Zhang, M. Oetgen
Nanochon, Children's National Medical Center,
Keywords: 3D printing, bioprinting, vascular, osteochondral
Summary:Osteochondral lesions of the knee are difficult injuries to treat [1, 2]. Despite improvements in the diagnosis of these lesions, optimal treatment remains elusive, likely as a result of the complex interactions between host factors and lesions specific factors. Lesions with disrupted cartilage that are unstable are especially difficult to treat in skeletally immature patients with current treatment methods leading to mixed results overtime . New and novel materials used to treat joint injury in these populations need to be compatible with industrial scale quality and economies of scale in order to serve as commercially viable implantable devices. We investigated the feasibility of using three-dimensional biologically inspired implants, manufactured using novel 3-dimensional printing techniques and synthetic bio-nanomaterials for treatment of osteochondral defects in a rodent model. An osteochondral defect was created in the trochlear groove of the left knee of 6-week old female Sprague-Dawley rats. A lateral parapatellar approach to the knee was used and the defect was created with a 2.0mm Kirschner wire. Four experimental groups included a blank control, a solid hydrogel implant and two experimental implants. Two different experimental implants were designed mimicking the complex micro-structure of the osteochondral transition zone and fabricated using a 3-d bioplotter: 1) a polycaprolactone and polyethylene glycol blended resin which is photocured via UV light and a nonoporous thermoplastic polyurethane (TPU) based material . The osteochondral defect was created and then immediately repaired by press-fitting the experimental implant into the defect. At 1 and 3 months samples were stained for hematoxylin and eosin (Figure 1). The surgical procedure was successful in all animals and all subjects survived to the follow-up time point. Histologic analysis (Figure 1) demonstrated some bone remolding and mostly formation of trabecular bone and marrow in the control, and in the PEG group. The PCL based experimental implant showed the formation of extensive fibrosis and scar tissue around the implant, with some bone remodeling. TPU based material showed the formation of fully remodeled bone around the implant, and some bone invading the implant microstructure. In an exciting development, a periosteum like membrane formed over the articulate surface of the implant. At 3 months this yielded the formation of new fibrocartilage over the implant surface, and fusing the implant to existing articulate cartilage. Additional in vitro study was performed to evaluate vascularized bone formation (Figure 2). It has been shown here that an experimental highly nanoporous TPU material can effectively be 3D printed into a complex microstructure implant for the repair of osteochondral lesions, accelerating bone growth with no fibrosis, as compared to controls and other experimental designs. The implant also showed signs of encouraging vascular and cartilage formation. There is great potential for a scaled up implant which could quickly graft to bone and even fuse to the healthy cartilage in a human patient’s defect.