• Growing Replacement Parts:
    U-M’s Tissue Engineering

    Posted on February 20th, 2012 admin No comments

    The notion that one day scientists will manufacture new body parts in the laboratory for patients who need them still seems like the kind of futuristic musings found in science fiction movies – right alongside teleportation and invisibility cloaks. But according to Dr. Scott Hollister, U-M professor of biomedical engineering, mechanical engineering, and surgery, lab-made body parts are not only possible, but their use in patients has already started and will likely accelerate in the future.

    Dr. Hollister is actually at the forefront of this incredible research. Working in partnership with a number of surgeons across many specialties, he has developed a method to recreate bone and other tissue out of biodegradable scaffolding and biologic material from patients.

    Using a combination of commercially available (Mimics from MaterialiseTM) anatomic computer aided design software (CAD), along with software his lab developed, Dr. Hollister designs the polymer scaffolding into porous customized shapes based on patient CT scans, and then “prints” them using laser-based systems. The scaffold pores are then filled with a patient’s own stem cells, along with growth factors and other biocompatible compounds, and implanted into the patient.

    Ultimately, the actual implementation process will vary, depending on the type of defect the implant is replacing. For small defects that do not need immediate re-vascularization (such as small holes in the scull), the scaffold, with attached growth factors and cells, can be implanted directly into the defect. For larger defects that need re-vascularization (blood vessels and blood flow) to survive, the prepared scaffold will first be implanted into a large muscle in the patient’s back where, over four to six weeks, blood vessels will grow and establish blood flow throughout the scaffold. This concept is known as a pre-fabricated flap.

    “The vascularization process has never been successfully performed, on the scale needed, outside of the human body; to overcome this obstacle, the patient will serve as their own bioreactor and incubate the replacement tissue,” says Dr. Hollister. “Over time, our goal is for new tissue and blood vessels to develop within the scaffolding and create an exact copy of the missing bone or cartilage. The scaffolding itself fully biodegrades and will dissolve as waste that is excreted from the body.”

    Dr. Hollister and colleagues, including oral maxillofacial surgeon Dr. Stephen Feinberg and neurosurgeon Dr. Frank LaMarca, have developed and successfully tested designed polymer scaffolds for mandible (lower jaw) reconstruction and spine fusion in pre-clinical animal models. To address the more complicated reconstruction of large defects, Dr. Hollister and oral maxillofacial surgeon Dr. Sean Edwards are currently developing a pre-clinical animal model to test the pre-fabricated flap concept, with funding support they anticipate from a recently submitted grant. If successful, the pre-fabricated flap concept could open the door for precise reconstruction of very large and complex tissue defects that require vascularization with multiple tissue types.

    “And because we’re using a patient’s own cells to grow the replacement, there is no issue with rejection like there is in other kinds of transplantation,” says Dr. Edwards. “We’re really just harnessing the body’s own mechanisms for growing new tissue – the scaffolding lets us guide the shape, but the patient’s own body really does the rest.”

    If ultimately successful, the team’s technique has broad implications for reconstructive medicine throughout the body, but would offer immediate good news for patients who need major jaw reconstruction. Right now, the current standard of care for jaw reconstruction is to create a replacement out of bone segment taken from the patient’s fibula.

    “Originally, we started out using the Mimics anatomic CAD software program to help Sean and other reconstructive surgeons design and model these complex craniofacial reconstructions as well as to create 3D physical models and templates for use in the actual surgery,” says Dr. Hollister. “It allowed the surgeons to carve the bone into a more precise copy of the patient’s original jaw.”

    To date, Drs. Edwards and Hollister have used this approach in 12 patient cases, using the software design, as well as 3D modeling capabilities available at U-M’s Medical Innovation Center. The approach has not only improved the aesthetic outcomes of the reconstruction, it also significantly reduced the time it took to perform the surgeries, which meant reduced risk for patients.

    “The design and modeling has been a huge help, but in the end, we still have to take bone out of a patient’s leg in order to recreate the jaw, which is really not an ideal solution. That’s why we’ve started thinking about alternatives,” adds Dr. Edwards. “Because the scaffolding material is endlessly flexible (unlike bone), and because we can design and perfect each replica in the lab before we ever enter the OR, we can produce results that are far superior to anything we could do with bone segments.”

    In effect, using the scaffolding technique, surgeons would no longer be limited to adapting other bones in the body to fit the face; they could custom design what they want for a particular patient and then grow it to be an exact copy of the original part. While widespread use in humans is still a ways off, Dr. Edwards plans to start testing the technique soon in patients without other options.

    “The mandible is the strongest bone in the body; and a working jaw, in terms of functionality, is fairly complex. If we’re ultimately successful with this project, it opens up the possibility to recreate virtually any part of the human skeleton,” says Dr. Hollister. “We’re already testing its use in tracheal reconstruction, and plan to explore its broader application in areas of orthopaedic surgery, spine surgery, and organ transplantation.”

    To learn more about this work, watch the U-M Alumni Association’s interview with Dr. Hollister. Or, find out how you can support tissue engineering efforts at U-M by contacting Greg Witbeck at germaine@umich.edu.

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