PInChPitt Innovation Challenge 2020

PInCh 2020 Finalists

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REPLICA

Categories:
Military medicine 3D milling & printing Cartilage Cosmetic surgery Ears Facial injuries Implants
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REPLICA: 3D-Sculpted Cartilage Implants

A custom-made cartilage ear implant that decreases complexity and operative time of facial surgeries, creating a state-of-the-art, high-precision cartilage milling process. 

Highlights

  • Due to its convoluted shape and visible position in the face, the reconstruction of the missing ear poses a complex challenge to the plastic surgeon; and unfortunately, the only existing options carry significant disadvantages.

  • To address this, we have invented REPLICA: an off-the-shelf, implantable ear framework made of pre-processed human cadaveric rib cartilage, sculpted into its final ear shape using a high-precision 3D freeze-micromilling (3DFM) process.

  • The REPLICA 3D-sculpted cartilage ear implants would remove donor site morbidity; decrease the number of surgeries and operative time; decrease surgical difficulty; and provide better integration to tissues—without the concerns of using a synthetic implant.

  • Ears are only the beginning: Our novel process to fabricate customized implants by 3D-sculpting cadaveric cartilage could potentially be used for a wide variety of applications in the body where cartilage is missing or defective, such as nasal reconstruction.

  • The PInCh award will allow us to take REPLICA to the next stage by helping develop and test our prototype, while obtaining key data to access larger funding sources and move this idea into clinical translation.

Problem

The ear is a critical, identifying feature of the human face, and its deformity can have profound effects on self-confidence and psychological development—as well as carrying functional problems, like the inability to wear prescription glasses. Ear anomalies can occur by either congenital causes (microtia and anotia) or acquired injury (e.g., trauma, bites, burns, or malignancy), affecting both children and adults.

Unfortunately, reconstructing the ear is particularly challenging due to its complex 3D geometry. Existing options carry significant disadvantages: the gold-standard technique involves harvesting the patient’s ribs and sculpting them into an ear, which is very technically demanding, time consuming, requires several stages, and creates considerable donor-site morbidity. The alternative is using a synthetic ear implant that is placed under the skin, which carries its own risks of exposure, severe infections, and full ear loss.

Bioengineering solutions proposed to date have not resulted in clinical translation mostly due to the lack of structural support and ultimate resorption. A better solution is needed.

Solution

Our innovation is called REPLICA: an off-the-shelf, implantable ear framework made of pre-processed human cadaveric rib cartilage, sculpted into its final ear shape using a high-precision 3D freeze-micromilling process (3DFM).

This ear reconstruction alternative combines the advantages of biologic cartilage (biocompatibility, integration, relative resistance to infection and ischemia, and structural support) and synthetic materials (customization, ease of use, and lack of donor site). The cartilage ear framework could be made patient-specific to resemble the contralateral ear using imaging or be standardized into set shapes/sizes of ears.

At the time of the operation, the surgeon would obtain the shaped cartilage ear and implant it in the standard approach used for current procedures. The human cadaveric rib cartilage (HCRC) utilized is already commercially available and proven safe for facial surgery.

Advantages to our approach would include: 1) elimination of donor site morbidity, while offering a non-synthetic alternative; 2) reduction in the number of surgeries, decreasing certain risks and cost; 3) reduction in operative time; 4) decrease in technical demand for the surgeon; 5) production of consistent, high-precision, customized shapes; 6) could grant a more widespread access to ear reconstruction procedures; 7) removes concerns of using synthetic prostheses with their associated complications.

Competition

The competitive landscape analysis below summarizes key features of this solution, and current competitors working to solve similar healthcare problems.

Team

  • Jesse Goldstein, MD, Craniofacial Plastic Surgeon, Associate Program Director of the Plastic Surgery Residency at the Children’s Hospital of Pittsburgh, University of Pittsburgh Medical Center. Principal investigator (PI) who specializes in pediatric craniofacial reconstruction. Will be the main surgical/clinical translation advisor, overseeing all steps and ensuring clinical applicability.

  • Burak Ozdoganlar, PhD, Ver-Planck Endowed Chair and Professor of Mechanical Engineering, Associate Director of the Engineering Research Accelerator at Carnegie Mellon University. Co-PI who will lead the engineering aspect of the project, and direct the design and execution of the prototype, experimental design, and the custom 3D-freeze-micromilling (3DFM) process.

  • Liliana Camison, MD, Senior Plastic Surgery Resident, University of Pittsburgh Medical Center. Responsible for project conception. Fascinated by ear reconstruction; has a background in craniofacial research. Will co-direct experimental design, execution of in-vivo work, data collection/analysis, and preparation of manuscripts/publications.

  • Lucas Dvoracek, MD, Senior Plastic Surgery Resident, University of Pittsburgh Medical Center. Project co-creator and 3D-printing aficionado with an interest in craniofacial research. Will co-direct experimental design, execution of in-vivo work, data collection/analysis, and preparation of manuscripts/publications.

  • Phil Campbell, PhD, Professor of Biomedical Engineering and Institute for Complex Engineered Systems, Carnegie Mellon University. Investigator with vast experience in tissue engineering and biomaterials (including cartilage and bone science) who will lead the biomechanical and in-vitro assessments.

  • Toygun Cetinkaya, PhD, Student at Carnegie Mellon University. Graduate student who will continue to execute the hands-on engineering aspects of the 3DFM process development, prototype production, and biomechanical testing.

Milestones

  • Milestone 1: To customize our 3D-freeze-micromilling (3DFM) process and produce an implant prototype in porcine cartilage. We will first refine our 3DFM process to allow for temperature control and optimal cartilage carving conditions, and then implement it to create complex shapes in porcine cartilage. In vitro and biomechanical studies will be completed.

  • Milestone 2: To produce an ear implant prototype using 3DFM in pre-processed human cadaveric cartilage. Once perfected in porcine samples, we will replicate the process in commercially available human cadaveric cartilage.

  • Milestone 3: To demonstrate that human cadaveric cartilage processed with 3DFM into a complex shape is able to preserve its detail and 3D structure over time without significant resorption after implantation. An in-vivo animal study will allow us to determine preliminary viability and shape preservation over time, as well as biological properties.

  • Milestone 4: To complete an improved prototype of REPLICA, our implantable ear framework made from cadaveric cartilage using 3DFM, ready for the next stages of development. Gathering experiences from the aforementioned work, we will deliver an improved prototype of an ear sculpted from human cadaveric cartilage with our 3D freeze-micromilling (3DFM) technology.

Path to Impact Plan

By the end of the funding period, we will have an improved prototype of our implantable ear made from human cadaveric cartilage using our 3D freeze-micromilling (3DFM) technology, with initial biomechanical and in-vivo data to support it. Our goal is to utilize this data to apply for further grant support (NIH, DARPA, AFIRM) for project development, as well as full patent within one year.

Later steps, after PInCh, will be to develop a strict sterilization process and appropriate manufacturing protocols. Since the cadaveric cartilage that we use as a substrate is already approved and commercialized, we anticipate simplified FDA clearance once we can demonstrate that our sculpting process does not significantly alter cartilage properties. Within the next three to five years, we would aim to create a start-up or license our product to one of the biomedical companies who already commercialize human cadaveric cartilage. Within five years, assuming successful preliminary work, we aim to try it in humans. Scientific publications and presentation of findings in academic settings will be pursued along the process.


"We restore, rebuild, and make whole those parts which nature hath given, but which fortune has taken away. Not so much that it may delight the eye, but that it might buoy up the spirit, and help the mind of the afflicted."

 -Gaspare Tagliacozzi (1545 – 1599), referring to Plastic and Reconstructive Surgery

Frequently Asked Questions

Why is facial reconstruction an important matter, including the reconstruction of ears?

Our face makes us recognizable to others; the representation of our being that allows us to transmit emotion and interact with the world. The ear is a critical, identifying feature, and its deformity can profoundly affect self-confidence and psychological development—as well as carry functional problems, like the inability to wear glasses.

Why not simply make cartilage grow in an ear shape, instead of carving it?

Although scientists have tried to create ears in the lab, none of them have successfully made it to clinical translation due to the consistent lack of structural stability. Under the pressure of the overlying skin, bioengineered or matrix-grown cartilage resorbs within weeks. However, cadaveric cartilage provides lasting structural support.

Are there additional applications for your cartilage 3D freeze-milling technique?

While our initial focus will be on the ear—chosen for its incredible complexity to manually reproduce—our novel process to fabricate customized implants by 3D-sculpting cadaveric cartilage could be used for a wide variety of applications where cartilage is missing or defective. Ears are only the beginning.

Is the human cadaveric cartilage safe? Can it be rejected or be immunogenic?

Fortunately, the main substrate (human cadaveric cartilage) of this project has already been studied in depth. Human cartilage is clinically available and in use, and research has shown no immunogenicity, good tolerance, and stability over time. Regardless, we will work hard to ensure safety and durability before clinical application.

Do you have any questions, feedback, or suggested contacts for the team?

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