Bioengineered growth factors lead to better wound healing

Scientists at École Polytechnique Fédérale de Lausanne have greatly improved the effectiveness of clinical growth factors, paving new strategies for regenerative medicine.

When we are wounded, our bodies naturally begin a process of repair of the damaged tissue. This process is mediated by biological molecules called growth factors, which are proteins that occur naturally in our cells and guide processes ranging from embryonic development to healing. Given their regenerative role in the body, growth factors have been investigated for use in drugs but with limited success. Publishing in Science, an EPFL group has used bioengineering to significantly improve the efficacy of clinical growth factors in the context of soft tissue and bone repair, while maintaining low and safe doses.

Growth factors are employed in a wide range of clinical applications that require . A major one is , which addresses tissue repair and . A number of growth factors have been explored in pharmaceutical compounds to promote new blood vessel and bone formation, and even to trigger the generation of granulation tissue – a collagen-rich tissue that forms at the site of an injury. Despite their extensive therapeutic exploration, growth factors have been very limited in terms of clinical translation, mostly because drug formulations often fail to properly reflect the biological function of growth factors in wound healing.

This video is not supported by your browser at this time.
Immunofluorescence imaging, (10 frames/s) of exposed dermis that was IV-injected with 100 μl of 10 mg/ml 155 kDa TRITC-dextran. Basal blood vessel leakage was recorded, while tissue was incubated with Ringer’s solution (saline). Immediately after, the exposed dermis was covered with Ringer’s solution supplemented with 10 μg/ml of appropriate vascular endothelial growth factor A and imaging of the dextran leakage in identical field of dermis was repeated. Credit: Science/AAAS

A group led by Jeffrey A. Hubbell at EPFL has found a way to vastly improve the efficiency of growth factors, while keeping their usage at low doses. The group screened 25 growth factors against six key proteins of the extracellular matrix – the supporting structure that surrounds organs and tissues in the body and is heavily associated with mediating the function of growth factors. Physiologically, the growth factors interact with these proteins to stimulate cell growth in damaged tissues by activation of receptors. In the screening test, the 25 growth factors bound to the six proteins with varying strengths, allowing the researchers to select one growth factor (PIGF-2) that showed the strongest binding across all six proteins.

By analyzing the sequence of the growth factor, the scientists isolated a 22-amino acid section that is responsible for the powerful binding of PIGF-2 to . By fusing that sequence to three growth factors they were able to increase their binding affinity by 2- to 100-fold, which could reduce the need for higher doses in the future. In addition, the bioengineered growth factors showed that they could mimic interactions in the formation of a blood clot, which would be additional beneficial to wound-healing.

The group also tested low-dose topical application of growth factors on diabetic mice, which are a common model for impaired wound healing. Compared to their unmodified counterparts, the growth factors containing the PIGF-2 sequence resulted in much faster wound closing and production of granulation tissue, and also led to a more pronounced new blood vessel formation, which is essential in sustaining the latter. The researchers also saw similar effects in bone repair, with the engineered growth factors showing a much higher deposition of bone tissue in rats with skull defects. Finally, they were able to show that the clinical side-effects of one particular growth factor could be alleviated by replacing it with its bioengineered counterpart.

The results show that a relatively simple modification can greatly improve the clinical use of growth factors, by making them more efficient, cost-effective and safe. The group is now fusing the PIGF-2 sequence to additional growth factors, which they can do in a virtually plug-and-play fashion. "Evolution has provided a close interaction between the and ", says Hubbell. "By re-engineering the molecules, we are able to exploit that interaction and open the way for clinical translation, turning these molecules into useful drugs." The researchers are now planning to extend their studies to larger animal models and eventually begin preliminary human trials.

More information: Martino MM, Briquez PS, Güç E, Tortelli F, Kilarski WW, Metzger S, Rice JJ, Swartz MA, Hubbel JA. 2014. Growth Factors Engineered for Super-Affinity to the Extracellular Matrix Enhance Tissue Healing. Science Feb 21 2014. Manuscript Number: science.1247663

add to favorites email to friend print save as pdf

Related Stories

Researchers regrow hair, cartilage, bone, soft tissues

Nov 07, 2013

Young animals are known to repair their tissues effortlessly, but can this capacity be recaptured in adults? A new study from researchers at the Stem Cell Program at Boston Children's Hospital suggests that ...

Regenerating orthopedic tissues within the human body

Feb 18, 2014

A team of Duke University biomedical engineers has developed a polymer scaffold for growing cartilage that includes gene therapy vectors to induce stem cells to produce the growth factors they need. The new ...

Recommended for you

Unlocking the secrets of pulmonary hypertension

2 hours ago

A UAlberta team has discovered that a protein that plays a critical role in metabolism, the process by which the cell generates energy from foods, is important for the development of pulmonary hypertension, a deadly disease.

New molecule sneaks medicines across the blood/brain barrier

7 hours ago

Delivering life-saving drugs across the blood-brain barrier (BBB) might become a little easier thanks to a new report published in the November 2014 issue of The FASEB Journal. In the report, scientists describe an antibo ...

User comments

Adjust slider to filter visible comments by rank

Display comments: newest first

soniabrito44
not rated yet Feb 20, 2014

Research Chemicals

We sell and supply high quality

and purity research chemicals

in both large and small

quantities worldwide.
Our shipping and delivery cost

is 100% safe and convinient.
We are ready to sell minimum

quantities and large deliveries

to the world of our product.
Below is a list of currently

available products we have in

stock.
pain killers . oxy adderal

etc..
Nopaine
Mephedrone (4-MMC)
Methylone (bk-MDMA)
MDAI
Ketamine hcl crystal powder
Dimethocaine (Larocaine/DMC)
Bulytone (bk-MBDB)
MDPV
JWH-018 / JWH-250,JWH-018,JWH-

073,JWH-200
JWH-250
2C-B
2C-B-FLY 2C-Bromo-Fly
2C-C
2C-D
2C-E
2C-I
2C-T-2
2C-T-4
2C-T-7
2C-T-2
5-Meo-DMT
4-Aco-DMT
Naphyrone

We have some other chemicals we

supply upon request.
You can therefore make your

order by contacting us

soniabrito44@gmail.com

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.