Bioprinting for bone repair improved with genes

Date:
April 12, 2022
Source:
Penn State
Summary:
Given enough time and energy, the body will heal, but when doctors
or engineers intervene, the processes do not always proceed as
planned because chemicals that control and facilitate the healing
process are missing. Now, an international team of engineers is
bioprinting bone along with two growth factor encoding genes that
help incorporate the cells and heal defects in the skulls of rats.



FULL STORY ========================================================================== Given enough time and energy, the body will heal, but when doctors or
engineers intervene, the processes do not always proceed as planned
because chemicals that control and facilitate the healing process are
missing. Now, an international team of engineers is bioprinting bone
along with two growth factor encoding genes that help incorporate the
cells and heal defects in the skulls of rats.


========================================================================== "Growth factors are essential for cell growth," said Ibrahim T. Ozbolat, associate professor of engineering science and mechanics. "We use two
different genes encoding two different growth factors. These growth
factors help stem cells to migrate into the defect area and then help
the progenitor cells to convert into bone." The researchers used gene
encoding PDGF-B, platelet derived-growth factor, which encourages cells
to multiply and to migrate, and gene encoding BMP-2, bone morphogenetic protein, which improves bone regeneration. They delivered both genes
using bioprinting.

"We used a controlled co-delivery release of plasmids from a
gene-activated matrix to promote bone repair," the researchers stated
in the journal Biomaterials.

Ozbolat and his team embedded the DNA for the protein in plasmids --
ringlike loops of DNA that can transport genetic information. Once the
DNA enters the progenitor cell, it begins to produce the appropriate
proteins to enhance bone growth.

The two genes were printed during surgery onto a hole in the skull of
a rat using a device very similar to an ink-jet printer. The mixture
was created to release a burst of PDGF-B encoding gene in 10 days and
a continuing release of BMP-2 encoding gene for five weeks.

The rats that received bioprinted genes with controlled release of BMP-
2 encoding gene saw about 40% bone tissue creation and 90% bone coverage
in six weeks compared to 10% new bone tissue and 25% bone coverage for
rats with the same defect, but no treatment.

"This method is better than simply dumping the growth factors," said
Ozbolat.

"If we do that, the amounts of proteins are finite, but if we use gene
therapy, the cells continue to produce the necessary growth factors."
Working with Ozbolat from Penn State were Kazim K. Moncal, graduate
student in engineering science and mechanics; Gregory S. Lewis, assistant professor and Hwabok Wee, postdoctoral fellow both in orthopedics and rehabilitation; Kevin P. Godzik, undergraduate in biomedical engineering:
and Elias Rizk, associate professor of neurosurgery.

Others contributing to the research include R. Seda Tigli Aydin, former
Penn State postdoctoral fellow now at Bulen Ecevit University, Turkey;
Dong N. Heo, former Penn State postdoctoral fellow now at the Kyung Hee University, South Korea; and Timothy M. Acri, former graduate researcher,
and Aliasger K. Salem, Lyle and Sharon Bighley Endowed Chair & Professor
in Pharmaceutical Sciences, University of Iowa.

The International Team for Implantology, the National Institutes of
Health, the National Science Foundation, the Osteology Foundation and
the Scientific and Technological Research Council of Turkey supported
this work.


========================================================================== Story Source: Materials provided by Penn_State. Original written by
A'ndrea Elyse Messer.

Note: Content may be edited for style and length.


========================================================================== Related Multimedia:
* Bioprinting_during_surgery ========================================================================== Journal Reference:
1. Kazim K. Moncal, R. Seda Tigli Aydın, Kevin P. Godzik,
Timothy M.

Acri, Dong N. Heo, Elias Rizk, Hwabok Wee, Gregory S. Lewis,
Aliasger K.

Salem, Ibrahim T. Ozbolat. Controlled Co-delivery of pPDGF-B and
pBMP- 2 from intraoperatively bioprinted bone constructs improves
the repair of calvarial defects in rats. Biomaterials, 2022; 281:
121333 DOI: 10.1016/ j.biomaterials.2021.121333 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2022/04/220412161608.htm

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