Pioneering 3-D Bioprinting Research Offers Glimpse into Future Treatment for Cartilage Injury and Osteoarthritis

Researchers at Penn State Health Milton S. Hershey Medical Center, in conjunction with bioengineers at Penn State’s Huck Institutes of the Life Sciences, are pioneering a new approach to repair cartilage damage to the knee. 3-D bioprinting technology offers the potential to correct issues ranging from small cartilage defects to entire knee replacements. The Centers for Disease Control and Prevention estimates that 22.7 percent, or 52 million, U.S. adults reported doctor-diagnosed arthritis in a 2010-2012 survey.¹

“Studies demonstrate that up to 60 percent of knee arthroscopies reveal cartilage damage to the knee,” says Aman Dhawan, MD, Penn State Bone and Joint Institute, a principal investigator and associate professor, Department of Orthopaedics and Rehabilitation, Milton S. Hershey Medical Center. “These chondral lesions have potential to progress to osteoarthritis, a burden to both patient and society in terms of cost, physical pain and disability.”

Current treatments for cartilage damage in the knee include cell-based solutions, cell-with-scaffold solutions, and marrow-stimulating techniques. Another involves injecting a gel of chondrocytes into the defect and covering it with a biological patch, with the anticipation that the cellular gel self-organizes into native cartilage. This method provides only limited success, however; the gel creates a filler tissue that has neither the mechanical properties nor the durability of native cartilage. None of these treatments can replicate the complex and necessary native microarchitecture and anatomy of articular cartilage.

Due to its well-formed architecture, osteoarticular allografts have demonstrated the best clinical success of the surgical options available for reconciling chondral and osteochondral lesions. However, these osteoarticular allografts are increasingly difficult to obtain, due to high demand and matching requirements. Average wait time for an osteoarticular allograft is 6-12 months, with patients experiencing continued debilitating pain and continued changes to the chondral surfaces of their knee. In addition to the significant supply and demand disparity, as with all allogeneic tissues, there remain concerns with infection and incorporation.

Researchers at Milton S. Hershey Medical Center are working to develop readily available, reliable osteochondral reconstructive grafts with durability, which recapitulates anatomy and promotes rapid, successful biologic integration utilizing 3-D bioprinting. This technique prints functional tissue using biological ink, which can include cells and components of the extracellular matrix, such as collagen. This work is currently in vitro and experimental, but researchers plan to translate it to the animal model soon, and someday potentially treat human beings with this technology in the operating room. The goal is to create structurally correct articular cartilage that replicates the normal anatomy and structure of articular cartilage. The articular cartilage also needs to contain a highly complex structure with multiple zones, each having a separate cell organization and extracellular matrix, and non-cellular biologic components.

“Currently, we have techniques to place cells into the defect or a scaffold with hopes that they self-organize into native tissue, but they do not,” Dr. Dhawan explains. “Using the 3-D bioprinting method, we think about it in reverse: ‘Can we start by envisioning the structure and then incorporate the elements, including cells, to fit that structure?’ The purpose of the cells that are inserted is to add to the organization and to help support the organization. The cells are printed into the structure in a very precise fashion that guides the production and organization of the extracellular matrix. With 3-D bioprinting, we are printing the architecture and organization.” This innovative technique can help to fill in small cartilage defects, as well as large defects, and is scalable to potentially resurface an entire joint and create a biological joint replacement.^3-6

3-D printed materials offer many potential advantages:

• Specific geometric and volumetric shapes can be created to fill a variety of different defects and can be applied to any size and location in the knee.
• Using autografts of cells from the patient rather than cartilage from a cadaver reduces the risk of disease transmission, decreases costs and eliminates the need for storage and transport of the material.
• The need for donor materials would be eliminated. Clinicians would use a sample of the patient’s stem cells to expand the patient’s own cell line; these stem cells then are driven towards cell lineages that are required for the printing, namely cartilage and bone.

Dr. Dhawan and colleagues recently received an extramural grant to support this work. The 3-D bioprinting research is an example of collaboration between the Department of Orthopaedics and Rehabilitation at Penn State College of Medicine, Penn State Health Milton S. Hershey Medical Center and the Penn State Department of Biomedical Engineering in University Park, Pa. Clinicians, basic scientists and bioengineers come together to solve an extremely relevant and debilitating clinical issue that would be impossible for any one entity to do individually. “Through the use and development of bioprinting, we are pioneering a novel approach to fabrication of zonal stratified articular cartilage for regenerative medicine to replicate native anatomy that, until now, our clinical techniques have been unable to do,” Dr. Dhawan says.

References

1. Centers for Disease Control and Prevention. Arthritis Data and Statistics. http://www.cdc.gov/arthritis/data_statistics/national-statistics.html. Accessed December 8, 2016.
2. Yu Y, Moncal KK, Li J, Peng W, Rivero I, Martin JA and Ozbolat IT. Three-dimensional bioprinting using self-assembling scalable scaffold-free “tissue strands” as a new bioink. Nature.com/Scientific Reports. June 27, 2016; 6:28714:1-11.
3. Datta P, Dhawan A, Yu Y, Hayes D, Ozbolat I. Bioprinting of osteochondral tissues: a perspective on current gaps and future trends. International Journal of Bioprinting. July 2017; [S.l.], 3(10), 109-120.
4. Leberfinger, A, Ravnic, D, Dhawan, A, and Ozbolat, IT. Concise review: bioprinting of stem cells for transplantable tissue fabrication. Stem Cells Translational Medicine. Aug. 24, 2017; 6(10), 1940-1948.
5. Dhawan A, Kennedy P, Rizk E, Ozbolat I. 3D bioprinting for bone and cartilage restoration in orthopaedic surgery. In revisions: Journal of J Am Acad Orthop Surg. November 2017; 25(11).
6. Dhawan A, Yang W, Ozbolat I. Fabrication of scaffold-free bioink “tissue strands” utilizing human ADSCs for 3-D bioprinting of articular cartilage. Abstract accepted: Magellan Society Meeting, Perthshire, Scotland. May 5-8, 2018.