Bone Regeneration and Infection Management using 3D Printed Scaffolds

Chronic osteomyelitis (OM) is a serious clinical problem in orthopaedic surgery, as approximately 112,000 orthopaedic device-related infections occur every year in the US alone, with an estimated overage in hospital costs of $15,000-30,000 per incident. While the infection rates over the past decade have been only 2% and 5% for joint prosthesis and fracture-fixation devices, respectively, these problems typically require a very costly and complicated multi-stage reconstruction techniques to first remove the infected devices and tissues and control the infection using antibiotic-laden cement spacers or bead, before attempting to replace the hardware and induce bone regeneration. Moreover, this multi-stage approach is associated with failure rates as high as 50% with catastrophic results that could lead to amputation or death.

Our lab is developing alternative fabrication technologies of spacers that can enhance the reproducibility of sustained release of antibiotics over a sufficient period to ensure eradication of bone infections and osteomyelitis, and potentially eliminate the need for the costly reconstruction procedures. Our hypothesis is that image-guided 3D printing of antibiotic-loaded, osteoinductive ceramic scaffolds can be effective in a single-stage reconstruction of infected nonunions with segmental bone loss.

Specifically, our work has led to the development of innovative strategies for adapting low- temperature 3D printing technology to fabricate osteoconductive calcium phosphate (CaP) scaffolds for applications in preclinical models of bone regeneration and infection. This technology has translational potential in medical image-guided reconstruction of massive bone loss in scenarios involving extremity bone and craniomaxillofacial trauma or infections.  Some specific foci of research include:

1. Development of novel mouse models with an established bone S. aureus infection in association with a fracture fixation plate to explore 3D printing alternatives to PMMA spacers n single- and two-stage reconstruction procedures of massive bone defects.
2. Adapting different modalities of low-temperature 3D printing of antibiotic-laden CaP scaffolds for sustained bactericidal delivery.
3. High-throughput screens (HTS) to identify candidates that are not only bactericidal against S. aureus normal colony phenotype (NCP) and biofilm, but also bactericidal to small-colony variant strain (SCV) and S. aureus colonization of canaliculi and submicron cracks in cortical bone.
4. μSiM-CA (Microfluidic - Silicon Membrane - Canalicular Array) as an in vitro screening platform for the genetic mechanisms of S. aureus invasion of the osteocyte lacuno-canalicular network (OLCN) of cortical bone during chronic osteomyelitis.
5. Stem cell strategies to vitalize and vascularize 3D printed scaffolds for bone regeneration in craniofacial bones including mandible and jaw.

Collaborators: Edward Schwarz, Paul Dunman, James McGrath

Funding: NIH/NIAMS P50 AR072000

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