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Otorhinolaryngology research lab Thomas Walks and Emilie RabutIn collaboration with Oren Friedman, MD, Director of Facial Plastic Surgery at Penn Otorhinolaryngology – Head and Neck Surgery, George R. Dodge, PhD, and his colleagues at the McKay Orthopaedic Research Laboratory in the Department of Orthopaedic Surgery and the Translational Musculoskeletal Research Center at the Philadelphia VA Medical Center, are finding ways to improve the use of autologous septal cartilage grafts in rhinoplasty and other routine surgeries.

“Our failures (in orthopaedics) in regard to joint cartilage regeneration where the need is for high mechanical strength, may become otorhinolaryngology’s successes”. — Dr. George R. Dodge, PhD

Symmetry, Stability, Form and Function in Rhinoplasty

One of the greatest challenges to surgeons performing rhinoplasty, perhaps, is the unpredictability of healing. If too much bone and cartilage is removed from the structure of the nose, the dorsum may collapse or warp over time; if too little, the desired effect is lost, and may be obscured by residual scarring. Additionally, trauma, systemic diseases, cancer defects, birth defects, or nasal infection may each result in cartilage loss and long term nasal deformities.

To compensate for these events in primary surgery, plastic surgeons rely on numerous grafts (such as batten, spreader and rim grafts) created from autologous cartilage transplanted to the nose to provide structural support, improve function and enhance appearance. Autologous septal and sometimes auricle or rib cartilage is considered ideal for grafting for its strength, malleability and endogenous origin (a natural bulwark against extrusion, inflammation and infection).

Cartilage manipulation

Analysis of the effect of manipulations on extracellular matrix loss from cartilage: proteoglycan glycosaminoglycan (GAG) assay: Demonstrates there is significant loss of matrix after the crushed and shaved manipulations and the least loss in moralized on a loss per cell basis. 

Wounding to Heal: Autologous Cartilage Preparation Successes and Challenges

Typically, the cartilage is removed and prepared by manipulation in one of four ways: scoring, shaving, dicing or crushing. Each of these maneuvers involves further preparation at the surgeon’s discretion to achieve pliability and form, with varying densities of scored and shaved cartilage, for example, and differing degrees of dicing and crushing.

Despite its advantages, the use of manipulated autologous septal cartilage is not a “sure thing”, and the rates of long term survival of the grafts is uncertain. In situations where the cartilage fails to engraft or tissues are resorbed, the patient may require revision surgery. It was clear that the degree of success could be linked to the survival of the cartilage cells transplanted.

Drs. Oren Friedman and Noam Cohen brought the issue of graft failure in rhinoplasty to the attention of Dr. George Dodge at the McKay Orthopaedic Research Laboratory several years ago. As a specialist in cartilage and chondrocyte biology, Dr. Dodge heads a Lab at the McKay and directs the Translational Musculoskeletal Research Center at the Corporal Michael J. Crescenz VA Medical Center in Philadelphia. His work has primarily focused on translational and regenerative medicine approaches as it relates to joint diseases and cells response to injury.

demo of manipulations

Demonstration of manipulations (top panel) and the loss of extracellular matrix (lower panel) by safranin-O red staining the glycosaminoglycan): Loss is greatest in (moderately) crushed samples.

Evaluating Cartilage Manipulation Methods

“I often collaborate with surgeons in orthopaedics and it seemed a natural extension to explore common ground with otorhinolaryngology,” Dr Dodge says, “and kept running into the idea that the cartilage manipulations I was hearing about had parallels to cartilage injuries we see in orthopaedics as a result of sport, accidents or combat trauma. The manipulations while necessary for increasing plasticity all likely injure the chondrocytes, the resident cells in cartilage.”

The surgeons’ needs were clear—to improve the cartilage to make it more plentiful, plastic and useful for reconstruction. However, Dr. Dodge’s years of practical experience with cartilage and research into approaches repairing cartilage damage and promoting cartilage regeneration lead to him to believe that an excessive degree of trauma to the cellular matrix of cartilage could be detrimental to its viability.

To evaluate this hypothesis, Dr. Dodge along with Dr. Friedman, and a team of residents and faculty colleagues from the Penn Otorhinolaryngology-Head and Neck Surgery conducted a study to ascertain which of the methods (scoring, dicing, shaving and crushing) caused more cell stress and death. Using bovine septal cartilage, the study compared each method to an unmanipulated control.

Crushed cell sample

Analysis of cell viability at at early and late time points after manipulations: Demonstrates the degree of dead cells is greatest in crushed samples and sustained after the initial crushing injury.

Which Prep is Best?

For each of the four preparation methods, the degree of cell stress, death and matrix damage correlated with the degree of injury. Moderate crushing was shown to cause the most damage compared to scoring, dicing or shaving. However, by cutting the cartilage surface, scoring and shaving caused enough injury to induce significant damage but also increased bending and plasticity. In general, dicing emerged as the least injurious method of manipulation.

Each manipulation should be considered carefully in specific clinical applications since less viable cells and more matrix damage could eventually distort the initial favorable post-operative result of rhinoplasty.

While none of the methods are ideal, crushing causes sufficient trauma to the cellular matrix to potentially negatively affect the success of any procedure using the technique. This joins a growing body of literature that suggests these surgical manipulations need to be carefully considered and alternatives explored.

The Take Away and Beyond – Engineering New Solutions

This cross disciplinary collaboration produced results with real translational application. “We’re trying to inform clinical practice by applying practical research approaches to clinical problems,” Dr. Dodge says. “It’s our hope that our study will inspire surgeons to consider the range of cartilage injury when selecting their surgical manipulation method.”

In the meantime, Dr. Dodge and his orthopaedic colleagues are actively exploring a variety of alternative approaches to septal autografting using cartilage tissue engineering approaches used in attempts to repair articular cartilage defects or damage from diseases such as osteoarthritis. Studies are underway to develop techniques and products to improve the stability and viability of cartilage grafting, and lessen the extent of injury. The advantage of septal cartilage is that it doesn’t have the strict requirement to bear high forces found in the joint.

Ideally with tissue engineering approaches we should be able to fabricate structurally similar cartilage analogs that one day may provide functionally suitable, viable grafts that will more readily and permanently restore structure and function for rhinoplasty and head and neck surgery.

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