Translating Bioprinting - Lab to Clinic

Pooja Venkatesh (Co-Founder and Co-CEO of Next Big Innovation Labs) sheds light on the transition of 3D Bioprinting from the lab to the clinic

20th August 2019

The world of 3D Bioprinting is a mixture of multiple disciplines. One of the key ingredients to a successful 3D Bioprint is the biotechnology. At Next Big Innovation Labs, we believe the biotechnology is what drives the engineering goals. Heading the Biotechnology, IP and regulatory efforts at NBIL is Mrs. Pooja Venkatesh. Pooja is a biotechnologist with a masters degree in business management from CASS University. With experience in working in cross-functional setups, Pooja currently works at NBIL. She is heading the scientific research activities, with a vision to bridge the abyss between transplantable organ requirement and availability. Let’s dive deep and understand the nuances of 3D Bioprinting..

Hi Pooja, tell us about your journey at Next Big Innovation Labs..

It all started in May of 2016, with a vision of 3D printing being used to revolutionize the healthcare sector. The four of us started out initially by making maxillofacial 3D models for doctors using patient specific scans. On further interactions with doctors and researchers, we realized that there is a growing need for customizable implants which would be made from biomaterials that could mimic the human scenario. This led us to explore the niche area of bioprinting, where 3D printing technology can be modified to handle biological materials and print them with micron level precision.  With the combined expertise of engineering and biotechnology in-house, we built our own bioprinter under the Make in India Initiative. We began interacting with the 3D bioprinting community in India to understand the problems faced by researchers during 3D bioprinting, these interactions combined with the technical expertise of having built our own 3D bioprinter had a two-fold effect.

Pooja showcasing NBIL’s Trivima at Bengaluru Tech Summit in November 2018

Firstly, it gave us an opportunity to work with researchers who approached us to 3D  bioprint scaffolds with their choice of biomaterials . Secondly, working with diverse biomaterials helped us in technical validation for our in-house built 3D bioprinter, Trivima. After validating our bioprinter, we decided to build our first line of bioprinted products – 3D bioprinted skin, Innoskin®. The reasoning behind bioprinting skin was that a ban on animal testing for cosmetic R&D was enforced by the EU in 2013, that many other countries are enforcing currently. This resulted in an immediate need for an ethical and an effective alternative for animal testing and 3D bioprinted skin can cater to this demand.

The hallmark for any innovative company lies in it’s IP, and we at Next Big Innovation Labs identify with this thought. Along the course of our journey we have filed for three patents, one on the process of bioprinting and two on our bioprinting technology.The long term vision for us at NBIL is to use our  technology to develop organs in the lab and bridge the gap between organ demand and availability.

Top – Image of NBIL’s propietary Bioink housed within the micro extrusion setup.        Bottom – 3D Bioprinted Scaffold right after printing

Can you explain the process of 3D Bioprinting?

The whole bioprinting process can be split  into 3 stages – the pre-processing stage, processing and post-processing stage. During the first stage we have to choose an appropriate biomaterial which could be natural,synthetic polymers or  both. Biomaterials are chosen akin to the ECM (Extra Cellular Matrix) of the 3D bioprinted tissue of interest. After choosing the biomaterials, battery of tests are done to determine the rheological properties, printability and cytocompatibility of the Bioink. The next stage would be the actual Bioprinting. It is crucial to maintain the rheological properties of the Bioink so that cell viability is not affected by the mechanical stresses exerted by the bioprinter. The 3D construct that is printed is called a scaffold, the scaffold provides a framework for the cells to grow.

The next crucial step is the crosslinking, which is done to ensure that the scaffolds are intact until they can create their own ECM. This step is most critical since the crosslinker chosen should crosslink the scaffold without affecting cell viability. As well as at the same time provide an internal microporosity for the cells to migrate within the scaffold. After crosslinking, the scaffolds are placed in media and kept in an incubator to maintain physiological conditions. The post processing stage is most fascinating. The cells migrate inside the scaffold and form cell-cell interactions like they would inside our body. The cells would ultimately metabolize the scaffold to form their own ECM and finally form the tissue.

Can you tell us a little about Innoskin®?  What are its applications?

InnoSkin® is 3D bioprinted skin tissue and the first of its kind in India. It has been developed using our patented bioprinting technology and processes. InnoSkin® is a cutting edge alternative to current in-vitro models for testing used in cosmetic, ingredient and pharmaceutical R&D.

“3D Bioprinted skin can enable testing with multiple prototypes at the same time. The studies pertaining to mode of action involving the biochemical pathways can be carried out using 3D Bioprinted skin models with ease following even the invasive analytical techniques which is not possible with human volunteers.” – Dr. Rajan Raghavachari – Global expert in cosmetic research & innovation and advisor to Next Big Innovation Labs

The first in the line of Innoskin® products is Innoskin® HE (Human Epidermis). InnoSkin® HE can be used for a plethora of tests, like skin irritation, corrosion and skin hydration to name a few. Currently these tests are being conducted on cadaver skin, pig skin,animal models and 3D Modelled Skin.

InnoSkin® FT comprises of the dermal and the epidermal component of skin. InnoSkin® FT  will be used for cosmetic ingredient testing and for drug efficacy and toxicity tests for topical applications. InnoSkin® provides a cost effective, accurate and time saving solution to current models that are used for testing. The InnoSkin® HE and InnoSkin® FT will outplay the current models used, in terms of repeatability and batch wise consistency.

Innoskin® Clinical is the ultimate goal of developing Innoskin® products, to develop 3D bioprinted skin using patient specific cells in the lab. This can be used to treat burn victims and for wound healing applications.

Top – Scanning Electron Microscope Image 3D Bioprinted Skin Scaffold

Middle – No Animal Testing Symbol – Source – Google 

Bottom – 3D Bioprinted Skin Scaffold

How long will it take us to get 3d bioprinted tissues for implants? or for wound healing?

The 3D bioprinting industry is growing leaps and bounds since its inception. Antony Atala pioneered in this field when he transplanted a 3D bioprinted urinary bladder more than a decade ago, which is still functional today. This shows us the future of 3D bioprinting and how it can be used to develop fully functional organs. There has been a lot of progress made by the 3D bioprinting community. Researchers across the globe are using  bioprinting to develop complex organs like heart, kidney and lungs to name a few. Although these organoids are a few years away from being translated into fully functional organs, they reinforce the fact that 3D bioprinting technology is the answer to organ transplantation. The researchers are using various 3D bioprinting technologies to get the placement of different cells in the bioprinted construct similar to the in-vivo scenario.

Apart from the aforementioned efforts, the community is also tackling the issue of achieving vascularization within these 3D bioprinted constructs. Bioprinting multiple cell types and precise vasculature within a 3D bioprinted construct will allow us to move closer to fully functional organs. Fully functional 3D bioprinted organs will have to clear the regulatory guidelines before it can be used for organ transplantation. In this light, the USFDA has finalised two guidance documents in February, 2019 under the Regenerative Medicine Advanced Therapy (RMAT) policy. The aim of these guidelines is to provide an opportunity to researchers, industry and clinicians, working with cutting edge technologies like 3D bioprinting, to fastrack breakthrough therapies that can positively impact patients lives.

The ban on animal testing for cosmetic products in the EU and the in-vitro toxicology testing have driven the adoption of 3D bioprinting technology and products. From an ethical standpoint, one must always look at how technological advancements can improve the quality of life of a patient suffering from terminal illness. Hence with this goal in mind, we at NBIL are developing Innoskin® Clinical which can positively impact the lives of people.