Periodic Reporting for period 1 - CBIT (Customisable Bioink Technology Platform)
Okres sprawozdawczy: 2017-03-01 do 2017-08-31
Podsumowanie kontekstu i ogólnych celów projektu
Three- dimensional (3D) printing, has been widely proposed in tissue engineering to restore, replace or regenerate defective tissues. Currently, there are only a handful of companies that offer commercially ready-to-use bioink or kit for bioprinting. Most of the commercially available bioink kits are offered as companion product by the bioprinter companies and DIY hybrid hydrogel for bioprinting can be a false economy to end users. PeptiGelDesign Technologies offer a broad portfolio of biomaterials for soft and hard tissue engineering and drug discovery. The portfolio is comprised of synthetic hydrogels acting as extra cellular matrix environment for 3D cell culture experiments and bioprinting, which is supported with scientific evidences. Exploiting the Company’s know-how in self assembling behaviour of short peptide in water, PeptiGelDesign Technologies provide a platform of tuneable mechanical strength and functionalities so that researchers can control the flexibility of the 3-D architecture to meet their applications specific needs.
3D Bioprinting has the potential to revolutionise the fields of cell biology, biomedical science and regenerative medicine. The ability to print autologous 3D tissues with exacting ECM requirements and special arrangement of biological molecules could enable: the production of customised tissue implants, hence reduce / remove the need for tissue donation; the production of disease models for the development of personalised medicines; and eliminate the use of animals in research or safety testing.
PGD Bioink Technology Platform will play a role in growing the global biotechnology sector by providing researchers with a fast and accurate method of producing large volumes of 3D cell culture models. The life science sector contributes significantly to the global economy (JLL, 2014). Scale up of 3D cell cultures could be used for; pharmaceutical development, toxicity testing, personalised diagnostics and regenerating tissues. Drug toxicity results in the failure of 16% of drug candidates and lack of efficacy results in the failure of a further 21% of candidates (Moore, 2003). The cost of drug candidate failure can run into the $100’s millions (The Economist, 2014). PGD bioink and disposable mixing chamber will reduce drug candidate rejection and decrease time to market by delivering a ready to use model for drug development in the pharmaceutical industry.
The objectives of the Phase 1 feasibility study:
• Technical / practical feasibility: Conduct pilot studies of 3D Bioprinting using PGD peptides, with and without
the inclusion of cells. This will enable PGD to assess the need for formulation alterations, gather initial 3D
Bioprinting data and conduct a technical feasibility assessment of the technology.
• Competitor analysis: Investigate competitor’s technology and compare to PGD’s proposed bioink and
disposable mixing chamber system. Potential future partners will also be identified.
• Intellectual property landscaping: Ensure PGD has freedom to operate and conduct a thorough IP review.
• Economic feasibility & risk assessment: Explore market feasibility and produce a suitable market entry plan,
including a pricing structure. The global size, growth and market dynamics will in explored and an appropriate
exploitation and dissemination strategy will be produced.
• Completion of business plan: Integrate technical, commercial, market, operational, and IP feasibility studies to
produce a coherent business plan. The business plan preparation will also provide PGD with a development to
commercialisation timeline and RoI timescales.
• Prepare and apply for SME Instruments Phase 2.
3D Bioprinting has the potential to revolutionise the fields of cell biology, biomedical science and regenerative medicine. The ability to print autologous 3D tissues with exacting ECM requirements and special arrangement of biological molecules could enable: the production of customised tissue implants, hence reduce / remove the need for tissue donation; the production of disease models for the development of personalised medicines; and eliminate the use of animals in research or safety testing.
PGD Bioink Technology Platform will play a role in growing the global biotechnology sector by providing researchers with a fast and accurate method of producing large volumes of 3D cell culture models. The life science sector contributes significantly to the global economy (JLL, 2014). Scale up of 3D cell cultures could be used for; pharmaceutical development, toxicity testing, personalised diagnostics and regenerating tissues. Drug toxicity results in the failure of 16% of drug candidates and lack of efficacy results in the failure of a further 21% of candidates (Moore, 2003). The cost of drug candidate failure can run into the $100’s millions (The Economist, 2014). PGD bioink and disposable mixing chamber will reduce drug candidate rejection and decrease time to market by delivering a ready to use model for drug development in the pharmaceutical industry.
The objectives of the Phase 1 feasibility study:
• Technical / practical feasibility: Conduct pilot studies of 3D Bioprinting using PGD peptides, with and without
the inclusion of cells. This will enable PGD to assess the need for formulation alterations, gather initial 3D
Bioprinting data and conduct a technical feasibility assessment of the technology.
• Competitor analysis: Investigate competitor’s technology and compare to PGD’s proposed bioink and
disposable mixing chamber system. Potential future partners will also be identified.
• Intellectual property landscaping: Ensure PGD has freedom to operate and conduct a thorough IP review.
• Economic feasibility & risk assessment: Explore market feasibility and produce a suitable market entry plan,
including a pricing structure. The global size, growth and market dynamics will in explored and an appropriate
exploitation and dissemination strategy will be produced.
• Completion of business plan: Integrate technical, commercial, market, operational, and IP feasibility studies to
produce a coherent business plan. The business plan preparation will also provide PGD with a development to
commercialisation timeline and RoI timescales.
• Prepare and apply for SME Instruments Phase 2.
Prace wykonane od początku projektu do końca okresu sprawozdawczego oraz najważniejsze dotychczasowe rezultaty
The work has been focused exclusively on two following theme: Technical and Operational Feasibility study, a Business Plan and Financial Feasibility study .
Technical and Operational Feasibility study
PeptiGelDesign hydrogels have been characterised to ascertain product requirement specifications for cell encapsulation and extrusion.
• Cell Encapsulation: Independently of the nature of PeptiGelDesign hydrogels and their pH pre-buffering with cell culture media, cell survival rate remains acceptable for cell culturing and bioprinting applications.
• Hydrogel Printability:
o A minimum shear thinning modulus (G’) is necessary to print the hydrogels with respect to the bioprinter used in this study. The hydrogel formulations must meet a 120 Pa threshold to print defined structure.
o The extrusion rate and fluid dynamics during the printing process has initially an impact on printed cell survival located on the edge of the constructs. This comment does not concern the bulk of the cell laden. Nevertheless, the cell population recovers after 72h.
• Demonstration: PeptiGelDesign hydrogels are suitable for 3D cell culture and bioprinting applications for the development of tissue models (breast cancer) and tissue engineering (bone)
From an Operational point of view, key activities/ partners and route to markets have been identified.
Key activities will be focused on R&D activities, Partnering with academics and KOLs. The company will also further its visibility and market credibility through important marketing/branding activities that will be supported by the constant company’s effort to meet regulatory approvals and product quality standards such as the CE mark. In terms of distribution channels, PeptiGelDesign will approach and supply its 3D bio-printing products to end users through direct sale, via bioprinter manufacturers and via life science distributors. Direct sale, although time consuming and may be least cost effective at first, it will present PeptiGelDesign with a major marketing opportunity to build customer relationship and credibility. Many academic researchers at leading universities are also KOLs in their fields. Therefore, it is important to build a community by getting leading researchers to acknowledge the benefits of PeptiGelDesign’s bioprinting products and especially getting them to publish academic articles using bioink by PeptiGelDesign. If successfully implemented, these activities will transition to wider acceptance by R&D directors at larger pharmaceutical companies who keep a close eye at the latest developments that happens in academia too. Partnering with bioprinter and biotechnology companies based on complementary product lines will be mutually beneficial as it offers wider selection of solutions to end users.
In order to reach to reach out to various customers in Europe, North America and advanced Asia, PeptiGelDesign will engage with known large distributors that help other companies to sell their hydrogels and bioinks in these markets.
Business Plan and Financial Feasibility study
Because 3D bioprinting can also be referred to as the next generation 3D cell culture where precise spatial arrangement of cells, extracellular matrix (ECM) components, and biochemical factors are deposited layer by layer using a pre-programmed software and a bioprinter, we focused on 3D Cell Culture and Bioprinting markets
• 3D cell culture market
A range of 3D cell culture platform do exist today, namely, hydrogel, scaffolds, scaffold-free spheroid, bioreactors and microchips. The global 3D cell culture market size was worth around $465 million in 2016 , hydrogels dominated the market with a share of over 41% ($191 million). Analysts expect that the whole market will reach $1345.2 Million by 2021, at a CAGR of 23.6% during the forecast period of 2016 to 2021 with main markets being North America and Europe. 3D cell culture has suffered from slow market adoption due to the poor quality of the products on the market so far, their lack of compatibility with automated liquid handing system and lack of scientific evidence.
The 3D cell culture market is driven by increased investment in healthcare, R&D, and other research-related activities. The novel concept of customized 3D cell culture products has allowed small companies to enter the market. While there is a clear need to provide the market with an easy to use, ready to use generic and application specific bionk formulations, other opportunities lies in contract researching using 3D cell culture for toxicology and pre-clinical testing, drug discovery and therapeutic use.
• Bioprinting and Bioink market
The 3D bioprinting market is currently at an early stage of research and development. It is steadily emerging as an area that that has huge potential for both academic research, clinical and therapeutic applications. Researchers at leading medical universities and pharmaceutical companies use 3D bioprinting to print cells and build tissues. These printed cells and tissues are used for the preclinical assessment of disease models and drug development, including applications in predictive toxicology, absorption, distribution, metabolism, excretion, and drug metabolism and pharmacokinetics.
The bioink market segment is estimated to grow from $71.4 million to $135.9 million by 2021 CAGR of 13.7%. The bioprinting industry is segmented 5 types of users: Drug discovery and development (Pharmaceutical, toxicology services, biotechnology), Research (Support from funding agencies for innovative 3D approaches to study diseases such as cancer, developmental biology, stem cell and tissue engineering), Cosmetic (Cosmetic companies that do not use animal testing), Clinicals (Cardiovascular, craniofacial repair, orthopaedics, wound care) as well as those non healthcare related stakeholders such as agrochemical or veterinary sectors. These 5 pillars represented a $295M market size in 2016 and a growth forecasted to reach $2Bn by 2021 (43.9% CAGR)
• Product differentiation
One of the key advantage of PGD bioink is that it requires no post-printing processing, which makes it easily adaptable for high throughput screening. Other USPs include: printability, cell viability and control over cell behaviour, compatibility with cell/protein extraction from 3D matrices for cell counting or proteomic wok. Also, peer reviewed scientific evidences demonstrate the use of PGD bioink with various stem cell and primary cell types.
Other differentiators are: tuneable matrix stiffness, simple functionalisation, ease of use as the products are designed to be used at room temperature.
• Business Opportunities
Today, PGD bioinks (generic and customised products) and consumables to improve patient experience
Tomorrow, development of toxicology testing activities, customised reagent for specific applications and regenerative medicine
Technical and Operational Feasibility study
PeptiGelDesign hydrogels have been characterised to ascertain product requirement specifications for cell encapsulation and extrusion.
• Cell Encapsulation: Independently of the nature of PeptiGelDesign hydrogels and their pH pre-buffering with cell culture media, cell survival rate remains acceptable for cell culturing and bioprinting applications.
• Hydrogel Printability:
o A minimum shear thinning modulus (G’) is necessary to print the hydrogels with respect to the bioprinter used in this study. The hydrogel formulations must meet a 120 Pa threshold to print defined structure.
o The extrusion rate and fluid dynamics during the printing process has initially an impact on printed cell survival located on the edge of the constructs. This comment does not concern the bulk of the cell laden. Nevertheless, the cell population recovers after 72h.
• Demonstration: PeptiGelDesign hydrogels are suitable for 3D cell culture and bioprinting applications for the development of tissue models (breast cancer) and tissue engineering (bone)
From an Operational point of view, key activities/ partners and route to markets have been identified.
Key activities will be focused on R&D activities, Partnering with academics and KOLs. The company will also further its visibility and market credibility through important marketing/branding activities that will be supported by the constant company’s effort to meet regulatory approvals and product quality standards such as the CE mark. In terms of distribution channels, PeptiGelDesign will approach and supply its 3D bio-printing products to end users through direct sale, via bioprinter manufacturers and via life science distributors. Direct sale, although time consuming and may be least cost effective at first, it will present PeptiGelDesign with a major marketing opportunity to build customer relationship and credibility. Many academic researchers at leading universities are also KOLs in their fields. Therefore, it is important to build a community by getting leading researchers to acknowledge the benefits of PeptiGelDesign’s bioprinting products and especially getting them to publish academic articles using bioink by PeptiGelDesign. If successfully implemented, these activities will transition to wider acceptance by R&D directors at larger pharmaceutical companies who keep a close eye at the latest developments that happens in academia too. Partnering with bioprinter and biotechnology companies based on complementary product lines will be mutually beneficial as it offers wider selection of solutions to end users.
In order to reach to reach out to various customers in Europe, North America and advanced Asia, PeptiGelDesign will engage with known large distributors that help other companies to sell their hydrogels and bioinks in these markets.
Business Plan and Financial Feasibility study
Because 3D bioprinting can also be referred to as the next generation 3D cell culture where precise spatial arrangement of cells, extracellular matrix (ECM) components, and biochemical factors are deposited layer by layer using a pre-programmed software and a bioprinter, we focused on 3D Cell Culture and Bioprinting markets
• 3D cell culture market
A range of 3D cell culture platform do exist today, namely, hydrogel, scaffolds, scaffold-free spheroid, bioreactors and microchips. The global 3D cell culture market size was worth around $465 million in 2016 , hydrogels dominated the market with a share of over 41% ($191 million). Analysts expect that the whole market will reach $1345.2 Million by 2021, at a CAGR of 23.6% during the forecast period of 2016 to 2021 with main markets being North America and Europe. 3D cell culture has suffered from slow market adoption due to the poor quality of the products on the market so far, their lack of compatibility with automated liquid handing system and lack of scientific evidence.
The 3D cell culture market is driven by increased investment in healthcare, R&D, and other research-related activities. The novel concept of customized 3D cell culture products has allowed small companies to enter the market. While there is a clear need to provide the market with an easy to use, ready to use generic and application specific bionk formulations, other opportunities lies in contract researching using 3D cell culture for toxicology and pre-clinical testing, drug discovery and therapeutic use.
• Bioprinting and Bioink market
The 3D bioprinting market is currently at an early stage of research and development. It is steadily emerging as an area that that has huge potential for both academic research, clinical and therapeutic applications. Researchers at leading medical universities and pharmaceutical companies use 3D bioprinting to print cells and build tissues. These printed cells and tissues are used for the preclinical assessment of disease models and drug development, including applications in predictive toxicology, absorption, distribution, metabolism, excretion, and drug metabolism and pharmacokinetics.
The bioink market segment is estimated to grow from $71.4 million to $135.9 million by 2021 CAGR of 13.7%. The bioprinting industry is segmented 5 types of users: Drug discovery and development (Pharmaceutical, toxicology services, biotechnology), Research (Support from funding agencies for innovative 3D approaches to study diseases such as cancer, developmental biology, stem cell and tissue engineering), Cosmetic (Cosmetic companies that do not use animal testing), Clinicals (Cardiovascular, craniofacial repair, orthopaedics, wound care) as well as those non healthcare related stakeholders such as agrochemical or veterinary sectors. These 5 pillars represented a $295M market size in 2016 and a growth forecasted to reach $2Bn by 2021 (43.9% CAGR)
• Product differentiation
One of the key advantage of PGD bioink is that it requires no post-printing processing, which makes it easily adaptable for high throughput screening. Other USPs include: printability, cell viability and control over cell behaviour, compatibility with cell/protein extraction from 3D matrices for cell counting or proteomic wok. Also, peer reviewed scientific evidences demonstrate the use of PGD bioink with various stem cell and primary cell types.
Other differentiators are: tuneable matrix stiffness, simple functionalisation, ease of use as the products are designed to be used at room temperature.
• Business Opportunities
Today, PGD bioinks (generic and customised products) and consumables to improve patient experience
Tomorrow, development of toxicology testing activities, customised reagent for specific applications and regenerative medicine
Innowacyjność oraz oczekiwany potencjalny wpływ (w tym dotychczasowe znaczenie społeczno-gospodarcze i szersze implikacje społeczne projektu)
There are various different types of synthetic gels. However, many of synthetic hydrogel lack the biocompatibility and biodegradability to support cell proliferation and many require deleterious post-processing/curing mechanism (UV, thermos and chemical cross-linker). PGD synthetic peptide hydrogel, on the other hand, offers the advantages of both natural and synthetic hydrogel with the reproducibility and customisation of the synthetic polymer, and the biocompatibility, biodegradable and biomimicry of the natural ECM of the natural biopolymer, but without the additional of post-processing step.
In the present course of the project, cellular models of mice mammalian gland and human mesenchymal stem cells have been encapsulated. Further to high viability of the printed cell-laden in all PGD hydrogel products, and this independently of the printing rate, the mammalian gland models are currently analysed for casein protein production. Reaching this end point would validate the models to move with human cell donors hereby providing the healthcare community to understand and potential stratify patient exposed with life threatening diseases such as breast cancer. In parallel, the capacity to differentiate human mesenchemial stem cells into osteogenic cells supports the potential use of PGD hydrogel for translational medical application, such as bone regrowth using patient own stem cells.
In the present course of the project, cellular models of mice mammalian gland and human mesenchymal stem cells have been encapsulated. Further to high viability of the printed cell-laden in all PGD hydrogel products, and this independently of the printing rate, the mammalian gland models are currently analysed for casein protein production. Reaching this end point would validate the models to move with human cell donors hereby providing the healthcare community to understand and potential stratify patient exposed with life threatening diseases such as breast cancer. In parallel, the capacity to differentiate human mesenchemial stem cells into osteogenic cells supports the potential use of PGD hydrogel for translational medical application, such as bone regrowth using patient own stem cells.