3D bioprinting for chronic wounds

Technological advances are enabling the advancement of personalized medicine, which means that treatments can be tailored to the patient, rather than generic solutions. A research team is working on developing bioinks to print patches capable of promoting chronic wound healing, skin or bone regeneration. At the same time, anti-inflammatory drugs or antibiotics based on nanotechnology can be added.

This is the sequence of research and development by the team of Martin Desimone, Sofia Munigai and Pablo Antezana from the Institute of Chemistry and Drug Metabolism, a joint center of the University of Buenos Aires (UBA) and the National Council of Science. in Scientific Research Techniques (CONICET), Argentina.

Bioprinters can create patches that promote tissue regeneration, so that chronic wounds that are difficult to heal can be much faster using organically derived inks. They are also used for skin ulcers in diabetics, burns and bone regeneration.

In previous projects, the team of researchers had already created patches from molds, which they aimed at bone regeneration of the jaw, in collaboration with the team of Daniel Olmedo from the Faculty of Dentistry of the UPA, were able to test in laboratory animals.

„The printer offers reproducibility and reliability, if you make two connections they come out the same. Something that cannot be achieved in any other way,” Martín Desimone, professor at UBA and researcher at UBA and CONICET, explained to Investica Argentina.

„What this technology does is make personalized medicine possible,” Desimone added, „because you can create a scaffold or a patch with the therapeutic molecules you need, at the appropriate concentration. You can print something tailored to a specific patient.

Bioinks and nanomaterials

„We have been working with biomaterials for some time; specifically with various biopolymers such as collagen, alginate, and gelatin. What we are looking for is to develop a material that can be used for tissue regeneration and promote faster wound healing,” Desimone explained.

The interesting thing about these biopolymers like collagen is that they are one of the main proteins in the human body, which makes them biocompatible. Not only are they not rejected by the body, but they are accepted by the body and because they are porous, they promote cell growth. They form a support to which cells can easily adhere.

Because some of these biopolymers are fragile, researchers are taking advantage of nanotechnology. That is, the growth of systems at the nanometric scale, one billionth of a meter. At that scale, materials have different physical and chemical properties that are not found at other scales. That's why scientists choose nanotechnology when it comes to fighting certain defects in our body.

„The nanomaterials act as a reinforcement of the imprinted structure and also act as a reservoir to release various therapeutic molecules, for example, to transport antibiotics,” Desimone explained.

„In recent work with Sophia, we used silver nanoparticles with antimicrobial activity. „Thus, in addition to promoting tissue regeneration, we can prevent infections that are one of the main reasons for rejecting implants or making healing difficult.”

3D printing technology has revolutionized development in various design fields, and it is doing so in health as well. This has led to great advances in dentistry, for example, the creation of molds or prostheses. But knowledge is growing to apply it to other areas of health, such as printing organic tissues.

„A year ago we incorporated 3D printing technology, which allows us to design a scaffold that has a specific structure or shape for where we are going to use it. Then it fits perfectly to the implant site. „In this way we can create patches for soft tissues like skin, or very much that can be used for a bone defect. An object with a rough texture can be created, for example, to fit exactly where the missing bone is. And it helps regeneration.” , the expert pointed out.

Thinking about a patch to be printed takes a completely different development than working with a print. Not only do you need to think about the design and materials of the patch, but those materials can go from a liquid or semi-liquid bioink to a solid.

„It's a technology that has a lot of potential in health, and it hasn't really expanded yet, because there's still a lot of focus and a lot of research into trying to develop these bioinks, which have to flow to print, but not collapse with each layer that's printed,” Desimone explained.

“Once printed the patch is placed directly on the skin or bone. And since it's a biodegradable, bioabsorbable material, in principle, there's no need to remove it, which helps integrate with tissues,” he added.

A patch is made of a composite material with different layers and each of them has a different texture. A system that can only be achieved through bioprinting. „The idea is to combine different biopolymers, such as collagen, chitosan, alginate or something else. We are looking for it according to the purpose and properties of the bioengineering we are considering,” said Sofia Munikoy, doctor of chemistry, researcher at UBA and CONICET, responsible for this part of the project.

„Various active ingredients such as nanomaterials, anti-inflammatory drugs or antibiotics are integrated into BioIng, so that it has multiple functions. That is, it increases cell growth, allows healing and at the same time prevents infection and avoids swelling of the affected area. At the same time, with this structure, It is also possible to control the release of active ingredients,” Munigai said.

Research team members. (Photo: University of Buenos Aires / Argentina Investica)

Heals chronic wounds

„Our advances are aimed at wounds with healing problems, usually classified as chronic or burns, where the tissue is too damaged or exposed,” explained Pablo Antesana, another member of the team, researcher and professor at UBA and CONICET. Faculty of Pharmacology and Biochemistry of UBA. „Now I'm doing my postdoctoral fellowship, where we're looking for substances that promote healing.”

There are many events in the development of a bioink; The first is to select polymers, the most appropriate compounds for the job you want to tackle. Researchers must ensure that the material maintains the computer-designed structure when printed.

The next step is to print and study how the bioink works during this process. What temperature is required, what speed and pressure. After printing comes the third event, which involves adding some material or compound that changes or enhances the already printed structure.

„We recently did a work in which Sofia and Pablo integrated some nanoparticles into an already printed scaffold,” explained Martin Desimone. „These are silver nanoparticles, which have good antimicrobial activity. Nanotechnology offers good approaches to combat the emergence of resistance to antibiotics.”

„Once we understand how it works, that's when we move to thinking about real applications,” explained Pablo Antezana. „In general we try to work with compounds that are very expensive and already approved by ANMAT, that's important. We work with collagen and gelatin, there are different types of products on the market with these components,” continued Antesana. „There are also products with silver nanoparticles that we use. Working with this type of material that has already been used and approved allows us to think that anything we create in the future will be easier to approve.

Globally they are at the same stage of understanding this very promising bioprinting technology. There is no progress on a commercial scale yet, but this is a technology that could be used not only in the applications mentioned by the UBA team, but also in the pharmaceutical industry, called aesthetic and personalized medicine. (Source: Martín Cagliani / University of Buenos Aires / Argentina Investica)