The X-factor required for bio-printed growth success

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Bio-printed implants, optimised with growth factors, show promise in the repair of bone defects, tissue regeneration and vascularisation.

A number of recent studies have demonstrated that growth factors – the signalling proteins needed to stimulate cell growth and repair – could be key to developing therapeutics for a number of conditions including certain cancers, cardiovascular disease, hematologic-related conditions and repair of bone defects. 

Longevity.Technology: Growth factors are usually expressed during stages of vascular endothelial growth factor (VEGF) and bone morphogenetic protein (BMP). In previous studies, scientists have created therapies combining these two growth factors in order to accelerate bone defect repair.

Growing new tissue is all well and good, but it must be vascularised in order to be a success, as Michael Hufford of LyGenesis told us: “if a transplanted tissue or organ isn’t vascularized, then it doesn’t survive, much less thrive.”

However, the promise shown by these therapies has generally not been realised when it comes to larger phase 2 trials, with some growth factor clinical trials actually demonstrating adverse effects rather than the positive impact anticipated.

Temporal delivery of exogenous BMP-2 induces early bone healing via an endochondral ossification process. Source: OUP

However, a team of biomedical engineering, mechanical engineering and biomechanics researchers from the US, Ireland and the Netherlands may have developed a solution [1]. The multi-disciplinary team created 3D-bioprinted implants that were optimised with growth factors to encourage the processes of angiogenesis: where new blood vessels emerge from pre-existing vessels, and osteogenesis, new bone growth. 

Lead author Fiona E Freeman and fellow researchers used bio-inks with nanoparticles so they could print implants with distinct growth factors and then studied whether the rate of angiogenesis was dependent on the expression of vascular endothelial growth factor (VEGF).

 


 

“This demonstrates the potential of growth factor printing, a putative point of care therapy, for tightly controlled tissue regeneration…”

 


 

 

The team noted that the implants that contained a gradient of VEGF had higher levels of vessel invasion than those which were homogeneously loaded with similar protein levels. The printed implants retained levels of VEGF as well as localisation of spatially-defined bone morphogenetic protein (BMP) and demonstrated the healing of large bone defects while causing only minimal abnormal bone growth. 

When they conducted tests on their rodent models, they noted consistent healing patterns in the group which received the bio-ink implants. Looking at bone density maps within a 12-week time period from implantation, they discovered that the new bones in their study contained cortical-like bone which was similar to native bone. Vascularisation was clear, as was the formation of fibrous tissue, bone marrow and cartilage.

This latest study adds to a growing body of research involving growth factors of bio-inks in the Longevity field.

For instance, researchers at the Wyss Institute packed growth factors into hydrogel to inject skin at an injury site while Aubrey de Grey, who is chief science officer at the SENS Research Foundation has previously spoken to Longevity.Technology about how damage repair is key to future of Longevity therapeutics. 

It is now hoped that this new technique could be used for a wide range of therapies. “This demonstrates the potential of growth factor printing, a putative point of care therapy, for tightly controlled tissue regeneration,” said the report. 

While taking these tissue engineering technologies from the lab to the patient could still be a challenging process, the team now hope that by using their spatiotemporal growth factor delivery method to help to repair bone defects or to increase vascularisation of other 3D printed constructs, this technology could be used to control the regeneration of a diverse array of tissue types. 

Vascularisation: tick … now onwards to neural growth!

[1] https://advances.sciencemag.org/content/6/33/eabb5093/tab-pdf

Image by David Mark from Pixabay

Photo by Chokniti Khongchum from Pexels

Eleanor Garth
Deputy Editor Now a science and medicine journalist, Eleanor worked as a consultant for university spin-out companies and provided research support at Imperial College London and various London hospitals in a former life.

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