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03.15 Mind the Gap
Mind the Gap    
 

There are plenty of naturally occuring gaps in our skeletal system, like the open spaces surrounding our joints that allow for flexibility and movement. But there are also gaps that are caused by injury or congenital defects that interfere with movement and can be quite painful. New research by Dr. Melissa Grunlan and a team of researchers at Texas A & M University demonstrates novel remedies for filling in these skeletal gaps.

The most common unwanted gap in our skeletal system occurs when a bone is broken. Our bones have an incredible capacity to heal themselves after injury, and the basic process is the same no matter the size of the broken bone.

When a bone is broken, a space is created between the two parts of the original bone. Immediately after injury, cells begin to move into the space created by the broken bone to stop the bleeding and heal tissue damage. After a period of time (days to weeks, depending on the size of the injury), new cartilage cells are produced on either side of the gap, forming a bridge-like structure that becomes the basis for a single, fully-healed bone. Although it may take some time, bone cells then replace the softer cartilage tissue, and the space created by the broken bone disappears.

Principles of Fracture Healing


Unwanted skeletal gaps can also be caused by congenital birth defects, injuries or removal of tumors.

In addition to broken bones, unwanted skeletal gaps can also be caused by congenital birth defects, injuries or removal of tumors. In patients with congenital birth defects, bones or parts of bones may be missing entirely; in the case of tumors, the removal of large pieces of bone surrounding the tumor site may sometimes be necessary. In either case, the intervening space is so large or irregular that the bone tissue surrounding the area cannot bridge the gap, and proper healing cannot occur.

In these cases, medical intervention may be necessary to first fill in the gap, and then allow for bone growth and healing to occur. Current approaches usually involve the removal of some bone from other areas of the patient’s body such as the thigh bone, skull or jaw, which is then fitted and placed into the existing space. This is known as a bone graft or autograft.

There are two major problems associated with this procedure. First, it involves the creation of an additional injury to remove the bone from another part of the body, with the same risks as any surgical procedure. Second, the injured spaces are often irregularly-shaped: it can be difficult to mold the bone graft into the necessary shape. Without the proper fit, bone grafts are often resorbed partially or completely by the body entirely, leaving behind the unfilled/unhealed gap.

"This is why we think polymers could be so useful," explains Dr. Melissa Grunlan, Associate Professor of Biomedical Engineering and Materials Science & Engineering at Texas A & M University. "Unlike bone, certain polymers can be molded to an exact fit." Dr. Grunlan's laboratory is devoted to using the newest polymer technology to improve medical devices and regenerative therapies. Dr. Grunlan looks at current treatments to determine if she and her team can improve treatment outcomes with polymers.



The polymer foam

For bone healing, Dr. Grunlan and her team of researchers developed a new way to fill in gaps in bone. To create a scaffold for bone growth, Dr. Grunlan chose the polymer known as polycaprolactone (PCL). PCL has been used in other medical devices and is known to be biocompatible, meaning that it generally does not produce a negative response by the body and can perform its function. Using PCL, Dr. Grunlan developed a porous, temperature-sensitive foam that can be molded to fit any shape. This type of polymer is called a shape memory polymer; it changes shape when it is heated and locks into shape as it cools.

"This is why we think polymers could be so useful. Unlike bone, certain polymers can be molded to an exact fit."

To create the foam, Dr. Grunlan poured the polymer over a salt template. The polymer was then exposed to ultraviolet or UV light, which solidifies the connections between the polymer molecules to create a rigid, 3-dimensional polymeric structure, like a sponge. This structure is then placed into water to dissolve the salt template, leaving behind a porous foam. The pores are critical to the success of the polymer scaffold because they provide spaces for the bone cells to latch onto and grow and make new bone tissue. When the PCL is placed into warm saline, it softens and can be pressed to fit any space, including an irregularly shaped bone defect. When it cools, the foam locks into place, creating the perfect fit and good contact with adjacent bone tissue, which is critical for healing.



Shape memory process

After developing the scaffold, Dr. Grunlan and her team tested the material for cytocompatibility (i.e., non-toxicity to cells) and bioactivity, meaning the ability to promote bone cell attachment and growth as well as mineralization – the ability to stimulate mineralization which is helpful to bond the polymer to adjacent bone tissue). In cytocomptability tests, bone cells were exposed to the polymer and then examined for markers of cell damage. Results of these experiments showed that the PCL foam is non-toxic to cells. Tests for bioactivity determined that further cell attachment, growth and mineralization could be stimulated by coating the polymeric foam with a second polymer called polydopamine. As a result, the creation of the polymeric foam now includes coating the PCL with polydopamine.


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Face repairing bone


So far, experiments in the laboratory provide good evidence that the PCL foam could be an effective alternative to bone grafting. The next step is to test the foam in animal models with bone injuries. "We still have a long way to go," cautions Dr. Grunlan, "but we are hopeful that this new technology could really help a lot of patients."



Shape-shifting material could help reconstruct faces


Dr. Melissa Grunlan is Associate Professor of Biomedical Engineering and Materials Science & Engineering at Texas A & M University. Her research focuses on using polymeric technologies to improve medical devices and create new regenerative therapies. A chemist by training, Dr. Grunlan works in close collaboration with biologists, physicists, engineers and other chemists to ensure the success of her research. When not in the laboratory, Dr. Grunlan enjoys traveling, running, yoga, and reading.

For More Information:

  1. Zhang D, George OJ, Petersen KM, Jimenez-Vergara AC, Hahn MS, Grunlan MA. A bioactive "self-fitting" shape memory polymer scaffold with potential to treat carnio-maxillo facial bone defects. Acta Biomaterialia 2014, http://dx.doi.org/10.1016/j.actbio.2014.07.020

To Learn More:

Polymer Foam

  1. Grunlan Research Group. http://grunlanlab.tamu.edu/
  2. Hahn Tissue Lab (at Rensselaer) http://www.hahntissuelab.com/the-superstars/#DrMariahHahn
  3. Wired Magazine. “This Sponge-like Polymer Could Fix Facial Deformities.” http://www.wired.com/2014/08/bone-repair-polymer/
  4. “Polymer Solutions” Blog. “Polymers May Fill the Gap for Bone Growth.” https://www.polymersolutions.com/blog/polymers-may-fill-gap-for-bone-growth/

Congenital Defects

  1. World Health Organization. http://www.who.int/mediacentre/factsheets/fs370/en/
  2. Centers for Disease Control and Prevention. http://www.cdc.gov/ncbddd/birthdefects/index.html

Bone Grafts

  1. MedlinePlus. http://www.nlm.nih.gov/medlineplus/bonegrafts.html
  2. Cleveland Clinic. http://my.clevelandclinic.org/services/orthopaedics-rheumatology/treatments-procedures/bone-grafting

Written by Rebecca Kranz with Andrea Gwosdow, PhD at www.gwosdow.com



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Dr. Melissa Grunlan


Dr. Grunlan with Olivia George (right)


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