The RegenMed Development Organization (ReMDO) is a non-profit organization that manages a consortium of more than 60 industry and academic members to advance regenerative medicine manufacturing technologies.
In partnership with the US Army Medical Research & Materiel Command (USAMRMC), the Medical Technology Enterprise Consortium (MTEC) awarded ReMDO a five million, five-year programme to develop universal bioink with tunable mechanical properties for regenerative manufacturing of clinical products.
Biogelx joined the ReMDO Advanced Biomanufacturing Initiative in 2017 and have been collaborating with other consortium members, such as Wake Forest Institute for Regenerative Medicine (WFIRM), to achieve the overall objective of this program. The aim is to formulate a base bioink with a modular cocktail of cross-linkers that can be used to tune the mechanical properties of the hydrogel, both for bioprinting, and for adjusting the final stiffness of the bioprinted construct to match the stiffness of native tissues, ensuring optimal cell survival and tissue construct function.
Biogelx specializes in tunable peptide hydrogels and bioinks that can be configured to mimic specific tissue types, and are compatible with a range of 3D printing technology.
3D bioprinting is a novel and innovative method for the 3D fabrication of living tissue/organ-like structures through the deposition of small units of a substance known as a bioink. The bioprinting process relies on the deposition of either cell-laden droplets or cell embedding in a hydrogel to create such structures. The benefits from this technique include the reduced production times, an increased versatility, and the possibility to work under room temperature. Furthermore, this technology combined with patient’s medical imaging systems creates an opportunity of the fabrication of custom-made products. Such options could improve the match between implant and defect size, can reduce the time required for surgery and for patient recovery, and positively affect treatment success. In general, this possibility to tailor therapy, also known as personalized medicine, is promising for improving health care and, at the same time, decreasing costs.
Healthcare improvement by 3D bioprinted cartilage
Today, the available scaffold options for bioinks are hydrogels, decellularized ECM (dECM), or microcarriers. Hydrogels are the most commonly used bioinks, due to their swelling and lubricating characteristics that best match with cartilage properties, and their potential to induce cells towards a chondrogenic phenotype. They are semi-liquid hydrophilic materials composed of a network of natural or synthetic cross-linked polymer chains. The gel consistency allows easy casting into the desired shapes and a uniform mixing with cells and growth factors. Depending on their origin, hydrogels can be natural or synthetic. Synthetic biocompatible hydrogels have a huge protentional in tissue engineering since their properties can be custom-designed in a more controllable manner than natural hydrogels.
As we know, the chondral and osteochondral lesions represent one of the most challenging and frustrating scenarios for the orthopedic, and oral and maxillofacial surgeons. Articular cartilage is a hyaline tissue covering bone ends to enable free movements. Joint tissues consequently tend to deteriorate. The issue is that cartilage lesions fail to heal spontaneously, leading to the development of chronic conditions, thereby reducing the quality of life and work capacity of patients, resulting in enormous costs for health and social care systems.
Things you must know about articular cartilage
Three-dimensional scaffold-based bioprinting holds the potential of cartilage tissue regeneration.and may provide a viable alternative to current treatment modalities. This technique displays important advantages to mimic natural cartilage over traditional methods by allowing a fine control of cell distribution, and the modulation of mechanical and chemical properties. It is well known that cartilage seemingly displays a simple structure, in fact, it is characterized by a zonal architecture defining specific mechanical properties which are very difficult to reproduce artificially. The “superficial zone” represents the top 10–20% of the cartilage and is characterized by the highest cell density. Just deep to it, the “middle zone” represents the next 40–60% of the cartilage, and the “deep zone” the bottom 30–40%, which then is in direct contact with the subchondral bone. Moving deeper from the “superficial zone”, there is a progressive decrease in cell density and an increase in the amount of glycosaminoglycan. Furthermore, the chondrocytes in the different zones differ. In the “superficial zone”, the cells are small and flattened, while in “deep zone”, the cells are larger and round. Additionally, different types of proteins are present in the articular cartilage, and their secretion and prevalence differ among zones. In the “superficial zone”, the most represented proteins are clusterin, proteoglycan-4, and Del-1, while in “middle zone”, cartilage intermediate layer protein (CILP) is at its peak. The specific distribution of these proteins probably contributes to the “zone-specific functionality” of the cartilage.
Some scientists question strategies based on the use of zonally harvested cells, considering these as overcomplicated. Therefore, they are working on approaches that are based on the use of a single cell source coupled with adequate biochemical and/or biomechanical stimuli. Stem cells, already demonstrated to be valuable mediators for tissue regeneration, are also promising candidates for this technology. Many studies have been conducted using adult stem cells derived from different sources such as bone marrow, adipose tissue, muscles, synovial membrane, trabecular bone, dermis, blood, periosteum, and perichondrium.
Bioprinting Articular cartilage
Hydrogels are defined as “water-swellable, yet water-insoluble, cross-linked networks” that can provide multiple advantages in tissue engineering as cell carriers for the creation of a multiple tissues. The 3D environment that they provide is able to maintain a high-water content, which resembles biological tissues and, therefore, facilitates cell proliferation. There are a multitude of natural polymers (i.e., collagen, chitosan, hyaluronic (HA) acid, silk proteins, gelatin, and alginates) that are widely used as hydrogel materials for tissue-engineering applications. The main limitation of these hydrogels for tissue engineering is their inability to maintain a uniform 3D structure. To overcome this problem, the synthetic hydrogels, such as peptide hydrogel might provide solution. Peptide hydrogel can also provide natural microenvironment for cells, which is considered paramount in cartilage tissue engineering. Therefore, these products might play a key role in 3d bioprinted cartilage research in the next few years.
Opportunities for Collaboration
As part of Biogelx Academic Collaboration Programme, we offer academic incentives to researchers interested in incorporating our synthetic 3d bioink materials into new projects. If you are in academia, have interests in the area of 3D Bioprinting and are looking to collaborate then contact us, there is no cost to exploring potential collaboration opportunities.
Livia Roseti et.a. (2018) Three-Dimensional Bioprinting of Cartilage by the Use of Stem Cells: A Strategy to Improve Regeneration Materials 11, 1749; doi:10.3390/ma11091749
Yu Liuet.al. (2017) Recent Progress in Cartilage Tissue Engineering—Our Experience and Future Directions EngineeringVolume 3, Issue 1https://doi.org/10.1016/J.ENG.2017.01.010
Di Bella C et.al. (2015) 3D bioprinting of cartilage for orthopedic surgeons: reading between the lines. Front. Surg. 2:39. doi: 10.3389/fsurg.2015.00039
CPhI Worldwide, the world’s largest pharma trade show, drives growth and innovation at every step of the global pharmaceutical supply chain from drug discovery to finished dosage. Through exhibitions, conferences and online communities, CPhI brings together more than 100,000 pharmaceutical professionals each year to network, identify business opportunities and expand the global market.
This year, CPhI Worldwide will host more than 45,000 visiting pharma professionals, 2,500+ exhibitors from 153 countries during 9 – 11 October in Madrid, Spain. Biogelx will exhibit within the Scottish Pavillion (Hall 9 – Stand J40) and will present the company’s innovative 3D Cell Culture and Bioink technology.
If you are visiting the event, please make sure to stop by and meet our representatives, Elia Lopez-Bernardo, PhD and Sandy Bulloch for a chance to discuss the applications of Biogelx products in drug discovery and regenerative medicine.
If you want to secure time to speak with Elia and Sandy, please click here and arrange a meeting.
Interview with Mitch Scanlan, CEO, who speaks about the recent and future R&D and innovation at Biogelx.
What is Biogelx for those who may not have heard of the company’s novel 3D peptide-based hydrogels?
Biogelx is helping people working in translational science, drug discovery and tissue engineering by “making in vitro cell cultures more in vivo”. We do this through manufacturing and supplying 3D cell cultures that can be tuned to specific tissues and synthetic bioinks that are reproducible and easy to handle.
Our portfolio of biomaterials is comprised of synthetic peptide hydrogels that act as extracellular-matrix environments to support cell growth. In addition, the chemical and physical properties of our biomaterials can be precisely tuned to replicate the characteristics of specific tissues so that the cells experience and engage with a realistic 3D environment. These unique cell-matching capabilities enable pharmaceutical and cosmetic companies, medical researchers and academics to better predict the safety and efficacy of screened compounds before they enter expensive clinical trials.
What are the biggest challenges the 3D Cell Culture industry is facing today?
On the whole, the 3D cell culture industry is an exciting field in which to be operating. In fact, the global 3D cell culture is expected to grow by 15% between now and 2024 to $1.69bn. This growth is driven by a demand in the areas of stem cell research, tissue engineering, drug discovery and, in particular, toxicity testing. That’s because pharmaceutical companies are increasingly looking for in vitro models that better predict the safety and efficacy of compounds before they are studied in humans. A report by BIO in 2016 found that over 90% of drug candidates entering Phase I trials fail to make it to marketing authorisation and a recent report from Deloitte found that, as a result, the cost of bringing a drug to market increased from $1.5bn in 2016 to $2bn in 2017.
However, although the benefits of 3D cell culture over 2D screening are increasingly recognised there are considerations that prevent a wholesale adoption of phenotypic screening in industry.
Firstly, the development of cell-based models to identify more specific cell behaviours costs more than traditional, 2D high throughput screening and represents an additional step in the drug discovery process. This means the methods and outcomes need to be proven and validated in order to demonstrate value to industry. This takes time, requires investment and demands benchmarking that isn’t necessarily well established.
Secondly, this is an emerging field and awareness of the different technologies and evidence supporting them isn’t widespread. So, sharing of data, insights and education with industry is important. In addition, this emerging field doesn’t yet have the imaging and analysis techniques associated with it in the same way they exist for more traditional high throughput screening.
Finally, the need for industry to outsource these capabilities is clearly an opportunity for 3D cell culture providers but it also takes many organisations (pharmaceutical companies included) into the unknown territory of joint ventures and collaborations. Navigating intellectual property agreements and the development of new business models is something that requires time and an appetite for trying something new.
What is new for this year as opposed to the previous one at Biogelx?
This year we have been focusing on better serving the end user through the commercial transformation of the company. We have developed a new sales and marketing strategy that aims to educate, share data and provide insight. To achieve this, we’ve recruited additional science and commercial professionals, and we’ve increased our spend on Research and Development.
We recently launched our new 3D Cell Culture product range, which offers functionalized cell culture matrices in response to market demand and in October we will launch our new generation peptide-based 3D bio-ink portfolio (BiogelxTM-INK).
In addition, we have been supporting Masters and Ph.D. students who are developing an osteogenic sarcoma model, an osteoarthritis model, wound healing applications and 3D bioprinting application for biomimetic bone grafts. We have also collaborated with external partners on two cancer research projects and applied for funding for a third.
Can you tell us more about the future product and service developments at Biogelx?
After the launch of our new, tissue specific 3D cell cultures and our synthetic bioink this year we will be working to launch another product before the end of 2018. This product will retain the key features of our biomaterials and will be particularly interesting for researchers currently using Matrigel.
Beyond 2018, we will be working to realise our ambition of developing the biological capability within the company to complement the chemistry that makes our products unique. We are also extremely excited to be starting a research project that aims to make personalised cancer treatment a reality for the future.
Biogelx will host a live webinar on October 25; what do the audience gain from attending this webinar?
This webinar has been designed for industry researchers, translational scientists and academics working in drug screening, toxicity testing and cell biology. The audience will gain insight from leading academics into the role of 3D cell culture in preclinical biomedical research as well as the specific role of Biogelx’s 3D cell culture in stem cell research and developing liver models for toxicity texting. The speakers will provide insight and experience gained through their work at the Sanford I. Weill Medical College of Cornell University, the City University of New York, the University of Strathclyde and the University of Glasgow.
The webinar will provide insight into the increasing role of 3D cell culture techniques in providing more physiologically-relevant results to more traditional 2D culture systems. There will also be perspectives as to why hydrogels are the most promising option in the development of 3D cell cultures that mimic both the salient elements and mechanics of native ECMs. The audience will also see the evidence for Biogelx’s 3D cell culture products in stem cell research and in the development of liver models.
Biogelx is a biomaterials company designing and supplying a range of 3D cell culture products and tunable bioinks. We specialize in synthetic biology, hydrogel design and bioprinting, and offer research services and product customization to match our collaborators’ needs. We are delighted to collaborate with partners on a variety of applications.
Examples of our previous collaborations include the development of new hydrogel chemistries for a specific tissue, cell type or research application in applications such as cancer biology and stem cell research. We have also adapted and optimized the printability of our hydrogels for specific printer systems and are currently working closely with other experts in bioprinting to develop our materials further.
Opportunities for Research Projects
Opportunities for scientific collaboration are abundant between groups with similar interests and complementary strengths. In particular, academic collaborations are very important to generate key application data to provide evidence of the successful application of innovative new technologies. Moreover, through collaboration it is also possible to spread the risk and cost of a research project and establish connections with leading scientific expertise, which can increase the opportunities to succeed with your R&D.
Opportunities for Materials Supply
As part of our academic collaboration programme we understand the constraints of research budgets and Biogelx offer academic incentives to researchers interested in incorporating our synthetic biomaterials into new projects. By collaborating effectively with industry academia can benefit from early access and introductory offers on innovative products. If you are in academia, have interests in the area of 3D cell culture and are looking to collaborate then contact us, there is no cost to exploring potential collaboration opportunities.