The Challenges and Advances of Imitating Nature

Allevi Advanced Biomatrix additives bioink additives for 3d bioprinting tissue and organs on 3d bioprinter

One of the largest hurdles of in vitro cell culture has been to mimic conditions that closely resemble in vivo outcomes. Significant strides have been made to this end in the past decades with progress accelerating in more recent years.

One approach that has widely-contributed to progress in tissue engineering and regenerative medicine has been to imitate the human body as accurately as possible. Tissues and organs consist of a milieu of extracellular matrices with varying quantities and placements.

With the advances in 3D bioprinting, scientists now have another tool to move closer to engineering tissues and organs that are more in vivo-like. Employing 3D bioprinting, a variety of ECMs can be precisely deposited in more native formats. 3D bioprinters now have multiple dispensing heads that can simultaneously lay down the ECM with cells in tissue and organ-like configurations. Furthermore, discoveries have recently been made creating native bioinks that are compatible with 3D bioprinters. A combination of such advances and discoveries with 3D bioprinters and native ECM bioinks likely propel future advancements in tissue and organ fabrication.

Further, native collagen bioinks consisting of Type I collagen can also be blended with other ECM’s to formulate more in vivo-like bioinks. Some of these ECMs include Type I, II, III, IV, V collagens, hyaluronic acid, elastin (tropoelastin), fibronectin and vitronectin. ECMs play a major role in achieving the proper cell behavior, cell adhesion signals and binding sites.

In addition to formulating a more optimal ECM environment, cells can be pre-mixed with the bioinks and bioprinted. The cells, in many cases, have been shown to remodel the tissue. Cells secrete and deposit their own intrinsic ECMs, growth factors, cytokines and other biologically relevant components.

The combination of these advanced 3D bioprinters, and cell-laden yet native-to-the-body bioinks, greatly enhance the capabilities and tools available to tissue engineers and scientists.

Allevi is excited to begin offering a broad line of native extracellular matrix proteins from Advanced BioMatrix (ABM) to serve as additives to many of Allevi’s BioInks. Bowman Bagley, Director of Business Development at ABM, comments: “The bar is being raised each day as new publications come out. Researchers are beginning to reject non-native materials as new native, yet printable, bioinks have emerged and are commercially available. The quest to bioprint tissues and organs begins with bioinks composed of native proteins that best replicate a natural, in vivo-like cellular environment. Our goal is to provide all of the proteins that help best replicate the human body when bioprinting. To print native tissues, we need native bioinks.”

As we continue to try and control tissue design, Allevi continues to provide the tools that will allow scientist to most accurately represent human architecture.

Allevi Author: UPenn bioprints custom nasal defects

Allevi 2 bioprinter bioprints nasal bone nose cartilage

We're proud to bring you yet another #AlleviAuthor - this one from down the street at University of Pennsylvania.  Dr. Chamith Rajapakse's Lab at UPenn focuses on the development and application of image guided 3D bioprinting for personalized clinical applications.

In his most recent publication, Dr. Rajapakse bioprinted a scaffold that precisely matched a patient’s nasal septal defect, in both size and shape using the Allevi 2 bioprinter. This serves as the first step in a major goal to create patient-specific tissue engineered grafts for NSP repair and beyond.

Here at Allevi, we envision a future of truly personalized medicine. The research by Dr. Rajapakse and his lab brings this future that much closer within the bone, cartilage and muscle tissue types.  One can being to imagine the future of being able to reconstruct cleft palates, nasal septal perforations, broken bones, torn ligaments, vertebrae and so much more.

Read on for the abstract and check out the full publication here.

Abstract: Nasal septal perforations (NSPs) are relatively common. They can be problematic for both patients and head and neck reconstructive surgeons who attempt to repair them. Often, this repair is made using an interpositional graft sandwiched between bilateral mucoperichondrial advancement flaps. The ideal graft is nasal septal cartilage. However, many patients with NSP lack sufficient septal cartilage to harvest. Harvesting other sources of autologous cartilage grafts, such as auricular cartilage, adds morbidity to the surgical case and results in a graft that lacks the ideal qualities required to repair the nasal septum. Tissue engineering has allowed for new reconstructive protocols to be developed. Currently, the authors are unaware of any new literature that looks to improve repair of NSP using custom tissue-engineered cartilage grafts. The first step of this process involves developing a protocol to print the graft from a patient's pre-operative CT.

In this study, CT scans were converted into STereoLithography (STL) file format. The subsequent STL files were transformed into 3D printable G-Code using the Slic3r software. This allowed us to customize the parameters of our print and we were able to choose a layer thickness of 0.1mm.  A desktop 3D bioprinter (Allevi 2) was then used to construct the scaffold.

This method resulted in the production of a PCL scaffold that precisely matched the patient’s nasal septal defect, in both size and shape. This serves as the first step in our goal to create patient-specific tissue engineered nasal septal cartilage grafts for NSP repair.

Allevi Author: New platelet-rich bioink boosts healing

platelet-rich-bio-ink-could-boost-healing-of-3d-printed-tissue-implants-and-skin-grafts-allevi

New #AlleviAuthor coming at you! 

Platelets are a component of blood that play a crucial role in wound healing: they induce clotting! Remember the last time you nicked yourself with a kitchen knife? The platelets in your blood rushed to the site of the wound and coagulated to staunch the bleeding and start the healing process. But platelets don't stop there - they also release growth factors to help repair the tissue which is why it is increasingly common to mix them with plasma for use in treatment of wound care and post operative procedures. 

Researchers at MIT, University of Nebraska-Lincoln, and Massachusetts General Hospital used the Allevi #BetaBot to develop a platelet-rich bioink to boost the healing properties of 3D printed tissues and skin grafts.

"In less than a day, the platelet-rich ink had prompted enough cell migration to heal about 50 percent of a scratch on some artificial skin, whereas the platelet-less version had covered just 5 percent of it. The ink also demonstrated the other unique property that platelets can offer, which is its ability to call for ‘reinforcement’ cells. It encouraged more than twice as many mesenchymal stem cells to migrate towards it than the platelet-less version, in a 24-hour period. These stem cells can then develop into muscle, cartilage or bone."  🅰️🅱️🆎🅾️

As the field of 3d bioprinting matures, bioinks like this one will be crucial for organ replacement procedures to help with wound healing and tissue regeneration. 

Their findings were published in Advanced Healthcare Materials.

BBC's The One Show Visits Allevi Power User, Dr Sam Pashneh-Tala

BBC's The One Show recently stopped by Dr. Sam Pashneh-Tala's lab at the University of Sheffield to learn more about tissue engineering and 3D bioprinting.

Dr. Pashneh-Tala’s research is focused on developing novel tissue-engineered blood vessels for use in vascular surgery. Current strategies rely on autograft vessels; which are of limited availability, variable quality and are prone to infection and blood clotting. Using tissue engineering and 3d biofabrication techniques, Dr. Pashneh-Tala is developing methods to allow blood vessels of custom geometries to be produced.

Check out the video below to learn more about the amazing research that is being performed today in his lab and the future of 3d bioprinting:

Dr. Pashneh Tala's research is bringing the future of 3d bioprinted tissues and organs that much closer. We can't wait to see what he will do next.  

New Product Alert: Organ-on-a-Chip Kit

allevi organ on a chip organ-on-a-chip microfluidics PDMS carbohydrate glass volumetric inc vasculature

Organ-on-a-chip technology, developed by the Wyss Institute at Harvard, has had a revolutionary impact on the field of tissue engineering by allowing the creation of models that mimic organ function and model diseases in a device that fits in the palm of your hand.

We were amazed in 2012 when we read Dr. Dongeun Huh and Dr. Donald Ingber's paper in Science Translational Medicine that successfully created a diseased lung-on-a-chip. Their findings demonstrated the ability to identify a drug's life-threatening toxicity that went unnoticed through traditional experimental methods, such as animal testing models. It was a milestone achievement and it inspired us to learn more about tissue engineering and its possible impact on humanity.

Since then, however, organ-on-a-chip manufacturing has mostly remained unchanged. Conventional methods give you little freedom to easily customize and create inner-chip architectures for your experimental models. We think it's time for a change...

Today, we're excited to offer Carbohydrate Glass from Volumetric™ Inc. and published in Nature Materials in our new 3D Organ-on-a-Chip Kit. Carbohydrate Glass is an incredible sacrificial material that has excellent printability and makes high-resolution microchannels. This new bioink kit will provide you the ability to create custom 3D geometries within organ-on-a-chip devices and allow for design freedom to create custom in vitro organ systems that were previously not possible. 

Our mission here at Allevi is to get technologies like this one into the hands of researchers who can really make a difference. We have worked closely with Dr. Jordan Miller, co-founder of Volumetric Inc, to perfect the protocol for the Allevi platform. We believe that custom organ-on-a-chip designs will be a major area of innovation for the tissue engineering and pharmaceutical community. This new kit provides another unique high impact application for biofabrication to not only change the field today, but the healthcare industry tomorrow. We can't wait to see what you will do with it.