December 17, 2019

Top 10 Questions Received by RoosterBio Customer Support

Tom Rogers, Director, Global Customer Support
and Amy Permenter, Technical Support Specialist
Answered by: Amy Permenter, Technical Support Specialist and Tom Rogers, Director, Global Customer Support

1. Do you have a sales representative in my state or country?
Yes! RoosterBio has four outstanding Regional Account Managers:
RoosterBio has two talented Field Application Scientists (FAS), Xuan Xu and Joe Takacs, who can assist in the field with technical questions. John Getz is RoosterBio's Government Account Manager and can assist with government-related questions.  If you are unsure of who to contact, please contact Tom Rogers.

2. How do I request a quote for your products?
RoosterBio can provide a quote for any purchase. Contact your local Regional Account Manager or Customer Support at 240-831-4914.

3. I'm ready to make a purchase! What's next?
Great! We have three different ways you can purchase our products:
  • Website - www.roosterbio.com
  • Purchase Order - submit to your Regional Account Manager or Customer Support
  • Credit Card Purchase - submit a Credit Card Authorization Form (obtained from Customer Support) to your Regional Account Manager or Customer Support
4. How do you ship your products and how long does it take to arrive?
RoosterBio ships all over the world - 26 countries ... and counting!
  • For local orders in Maryland, we use a courier service for same day delivery. 
  • For US orders, we use FedEx overnight priority delivery. This is next day delivery and should arrive by 12:00pm.
  • For orders to Canada and Europe, we use FedEx and it usually takes 2-4 days depending on customs clearance.
  • For orders to Asia and Australia, we use FedEx and it usually takes 3-5 days depending on customs clearance. Note: we have used Expeditors and World Courier for some shipments to Asia.
5. What documentation is sent with the order?
  • For cell orders, you will receive an Expansion Protocol, QC Brief, Certificate of Analysis and Cell Product Insert.
  • For media orders, you will receive a Certificate of Analysis and the Media Product Insert.
  • For international customers, you will also receive a Material Safety Data Sheet for all products ordered. Depending on which country you are in, you could also receive a Certificate of Origin.
6. The products arrived! Now what do I do?
  • Place the cells in liquid nitrogen storage
  • For the RoosterNourish™ Media:
    • Store the RoosterBasal™ in 2-8°C refrigerator (protect it from light)
    • Store the RoosterBooster™ in -20°C freezer
  • Store the RoosterReplenish™ in -20°C freezer
  • Store the EV Boost™ in a 2-8°C refrigerator (protect it from light)
  • Store the RoosterCollect™ in a 2-8°C refrigerator (protect it from light)
7. I ordered my cells and media, but when my order arrived, I couldn't find the cells. Help!
Do not worry! RoosterBio sometimes uses a nest configuration in one large box when shipping cells and media together. Inside the large box is the RoosterBasal™ on cold bricks, along with a smaller box. The smaller box is layered with dry ice, the RoosterBooster™ and the cell vial. Please make sure to remove the RoosterBooster™ and dig deeper into the box for the cell vial.

8. I'm ready to use the RoosterNourish™ Media Kit. What do I do? How long can I use the media?
Bring the Media Kit to room temperature. In a hood, pipet the 10mL RoosterBooster™ into the 500mL RoosterBasal™. Once combined, store the media at 2-8°C for 2 weeks, ensuring that it is protected from light.

9. Do I need to heat inactivate the media?
No, you do not.

10. Can I request a specific lot of cells?
Absolutely! RoosterBio has a donor grid that includes age, gender, population doubling level (PDL), differentiation and flow markers. Contact Customer Support for the donor grid.

November 26, 2019

Generating MSC-EVs With A Scalable Manufacturing System

Authored by: Katrina Adlerz, PhD, Scientist, Analytical, Process & Product Development, RoosterBio

Scalability of EV Manufacturing is a Major Challenge
Previously, we discussed the emergence of MSC extracellular vesicles (EVs) as clinical therapies. However, a critical barrier in the development of MSC-EVs as a commercial therapy is generating the large amount of EVs that will be required per dose (1). A recent review estimated that the number of exosomes released from 2 million MSCs in 48 hours is equivalent to a single dose for a rodent (2), suggesting that similar to cell therapy, billions of cells will be required to manufacture an EV commercial therapy. In a recent survey, however, the majority of those working with EVs were working with less than 100mL of sample (3) indicating the lack of scalable manufacturing processes in the field. We have identified three keys that we believe are necessary to enable successful manufacturing of EVs for clinical therapies:
  • Generating the billions of cells needed with a scalable manufacturing process
  • Increasing the number of EVs generated per cell to maximize productivity
  • Optimizing downstream EV purification to increase concentration with minimal processing loss (to be addressed in future blog)
  • GMP quality supply chain takes years to develop. Starting with the right materials is critical.

More Cells Enable Production of More EVs
The first critical challenge to generating the EVs needed for product development and clinical therapies is growing the necessary numbers of cells. RoosterBio (RBI) high-volume cell formats and paired bioprocess growth medium are engineered for  scalable manufacturingto address this bottleneck. Figure 1 illustrates the ability of RBI systems to generate millions to billions of MSCs, which produce trillions of EVs, in an 8 to 10 day process. Our starting Working Cell Bank vial format and culture paradigm decrease manufacturing time and are scalable to yield the number of EVs required for clinical translation.

Scalable Process for MSC-EV Manufacturing
We recently introduced RoosterCollectTM-EV, a low-particle medium that is engineered for EV collection. This medium is designed to be complementary to RoosterBio MSCs and the RoosterBio bioprocess growth medium RoosterNourishTM. Together, these RBI products create a complete system for efficient cell growth and EV collection

Using these products, the optimized process (shown in Figure 2) is: 
1) Expand MSCs in RoosterNourish until at least 80% confluency 
2) Switch to RoosterCollect-EV 
3) Collect the conditioned medium

RoosterCollect-EV supports EV collection for at least two days with increasing particle concentration in the conditioned medium and collected particles in the size range expected for EVs (Figure 3).

This process works for both 2D flask culture and 3D bioreactor culture. Bioreactor culture allows for even greater MSC and EV yields with reductions in cost, labor, and time (see our poster presented at ISCT 2019). Also, conditioned media in 3L and 15L bioreactor culture had  greater particle concentration compared to the 2D flask system (Figure 4), which is at least partly explained by the increased cell density we can achieve in bioreactors (see our poster presented at ISEV 2019)

Increased Productivity for More EVs
A complementary strategy to a scalable cell manufacturing process is increasing the EV productivity (i.e. the number of EVs produced per cell). Recently-introduced EV BoostTM is a medium supplement that is designed as a tunable addition to RoosterCollect-EV medium. Depending on the number of EVs required, EV Boost can increase particle yield up to 5x and dramatically shorten collection times (Figure 5).

What’s Next in Scalable EV Production?
Optimizing EV yield will become increasingly important as EVs move to clinical therapies and EVs from billions of cells are required to satisfy dose requirements. RoosterBio’s complete system for MSC-EVs generates millions to billions of cells in 2D or bioreactor culture and trillions of EVs, this system also provides a scalable platform for increasing EV production. This, combined with optimized scalable downstream purification (a third key challenge in EV manufacturing, and subject of a future blog), will enable the success of EVs as clinical therapies. 

Rapid translation/transition of to cGMP production will drive the future of scalable EV production for years to come.

References:
1. Colao IL, Corteling R, Bracewell D, Wall I. Manufacturing Exosomes: A Promising Therapeutic Platform. Trends Mol Med. 2018;24(3):242-56.
2. Phinney DG, Pittenger MF. Concise Review: MSC-Derived Exosomes for Cell-Free Therapy. Stem Cells. 2017;35(4):851-8.
3. Gardiner C, Di Vizio D, Sahoo S, Théry C, Witwer KW, Wauben M, et al. Techniques used for the isolation and characterization of extracellular vesicles: results of a worldwide survey. J Extracell Vesicles. 2016;5:32945.

November 1, 2019

MSC-EVs Emerge as Clinical Therapies

Authored by: Katrina Adlerz, PhD, Scientist, RoosterBio and Divya Patel, PhD, Scientist, RoosterBio


MSC-EVs Emerge as a Cell-Free Therapy

Extracellular vesicle (EV) interest continues to increase as more evidence emerges about the ability of these lipid-bilayer membrane vesicles to elicit specific responses from recipient cells. EVs are secreted by most known cell types, including MSCs. Recently, many effects of MSC-based therapeutics have been attributed to their paracrine factors which includes MSC-derived EVs (1, 2). In particular, MSC-derived EVs have been shown to recapitulate therapeutic effects of MSCs in graft-versus-host disease (3)and myocardial ischemia (4), among others. Moreover, EVs derived from MSCs benefit from MSCs’ well-defined safety profile, with MSCs having been used in over 900 clinical trials. Given their therapeutic potential, EVs are on the rise as a novel clinical therapy for a broad range of applications. This interest is reflected in the high number of peer-reviewed publications in the past 10 years mentioning EVs (over 15,000), with 700 specifically on MSC-EVs (PubMed Search Results Oct 2019) and the larger presence of EVs at cell therapy conferences.

MSC-EVs as Drug Delivery Vehicles

In addition to their use as a cell-free therapy, there is also significant interest in using EVs as drug delivery vehicles. EVs are natural carriers of bioactive cargo such as proteins and RNA, which are protected by the lipid-bilayer membrane. Research efforts have focused on both exogenous loading of biological cargo and manipulating parent cells to engineer vesicles that contain cargo of interest. 

RoosterBio EVs

RoosterBio MSC-EVs were evaluated based on a guidance for defining EVs, as published by the International Society for Extracellular Vesicles (5). Particles collected from the conditioned medium of RoosterBio MSCs are in the EV size range, contain expected proteins and small RNAs, and have bioactivity in a wound healing assay (Figure 1).



Figure 1 A Particles collected from RoosterBio MSCs have diameters in the size range of 50 to 250 nm as measured by Nanosight and TEM. Western Blot shows EVs express expected proteins: ALIX, TSG101, CD63, CD9, and CD81. Collected EVs contain primarily small RNA. Conditioned medium has bioactivity in a standard in vitro wound healing scratch test.

Challenges Facing the Field

While EVs hold much promise as a cell-free therapy or drug delivery vehicle, there are some key challenges in the translation of successful EV therapies, including generating the needed number of EVs. In our next blog we will discuss some of these key challenges that need to be addressed to enable the success of EV therapies and RoosterBio’s progress in meeting the needs for EV product development, clinical trials, and commercial therapies. 


References
1. Phinney DG, Pittenger MF. Concise Review: MSC-Derived Exosomes for Cell-Free Therapy. Stem Cells. 2017;35(4):851-8.
2. Caplan AI, Correa D. The MSC: an injury drugstore. Cell Stem Cell. 2011;9(1):11-5.
3. Kordelas L, Rebmann V, Ludwig AK, Radtke S, Ruesing J, Doeppner TR, et al. MSC-derived exosomes: a novel tool to treat therapy-refractory graft-versus-host disease. Leukemia. 2014;28(4):970-3.
4. Lai RC, Arslan F, Lee MM, Sze NS, Choo A, Chen TS, et al. Exosome secreted by MSC reduces myocardial ischemia/reperfusion injury. Stem Cell Res. 2010;4(3):214-22.
5. Lötvall J, Hill AF, Hochberg F, Buzás EI, Di Vizio D, Gardiner C, et al. Minimal experimental requirements for definition of extracellular vesicles and their functions: a position statement from the International Society for Extracellular Vesicles. J Extracell Vesicles. 2014;3:26913.

September 18, 2019

Meeting the growing needs of the perinatal RegenMed Industry: the only Umbilical Cord hMSC (hUC-MSC) system designed for today’s translationally focused research and product development

Authored by Iain Farrance, PhD, Technical Marketing Associate


Introduction

Human mesenchymal stromal cells (hMSC) are considered the "workhorse" of Regenerative Medicine (RegenMed).  hMSC are a critical starting material in a growing variety of established and emerging RegenMed products, including cellular therapies, cell-based gene therapies, hMSC-derived extracellular vesicles (EVs), and bioprinted engineered tissues (Olsen, 2018). Accordingly, there have been greater than 100 clinical trials initiated each year since 2011 using hMSC from various sources (database purchased from celltrials.org) across a host of indications and therapeutic strategies (clinical trials.gov).  hMSC have benefitted from having an excellent safety profile, and there have been nine (9) products approved globally over the last 10 years. The growth in use of hMSC in a variety of product types has created the opportunity to standardize the supply chain and provide economies of scale for a rapidly growing industry. RoosterBio was founded to industrialize and standardize the RegenMed supply chain and to radically simplify the incorporation of living cells into therapeutic product development. Our goal is to have the same impact on the RegenMed industry that Intel had on the computer industry.

Use of Human Umbilical Cord-derived MSCs (hUC-MSC) in research and clinical trials (CT) has grown rapidly over the last 10 to 15 years with quickest adoption in APAC (Figure 1, Davies, 2017; Zhao, 2018; Moll, 2019). hUC-MSC publications per year increased 19-fold increase from 2006 to 2016 (Zhao, 2018). CT with hUC-MSC have shown a similar growth pattern as publications. hUC-MSC are the second most used hMSC type in CT (Moll, 2019) and 178 CT using hUC-MSC were registered, are ongoing, or were completed between 2007 and 2017 (Couto, 2019). In fact, >30% of hMSC trials registered in 2019 use hUC-MSC as the cell source.  These drive the need for hUC-MSC to use in product development. Until now, IP surrounding hUC-MSC has been a primary roadblock to the widespread adoption of hUC-MSC. We have collaborated with leaders in Wharton’s Jelly/umbilical cord hMSC at Tissue RegenerationTherapeutics Inc. (TRT) and have brought to market a complete bioprocess cell and media system. RoosterBio’s hUC-MSC are available for licensing and are provided in scalable formulations and cGMP compatible processes that enable anyone to obtain hUC-MSC in numbers needed for incorporation into RegenMed product development.



Until now RoosterBio has paired our batch (2D) and fed-batch (3D bioreactor) bioprocess media systems with hMSC from two sources: adipose-derived (hAD-MSC) and bone marrow-derived (hBM-MSC and xeno-free (XF) hBM-MSC). RoosterBio’s launch of our XF hUC-MSC (RoosterVial™-hUC-MSC-XF) introduces the first umbilical cord-derived hMSC in the North American and worldwide market designed to meet the quality and volume needs of today’s translationally focused cell therapy product developers. For RoosterBio’s hMSC product lines see here.

RoosterBio’s RoosterVial-hUC-MSC-XF and RoosterNourish™-MSC cell and medium bioprocess system has several key advantages over the limited number of suppliers of perinatal hMSC. Being XF, and manufactured with RoosterBio’s existing cGMP compatible processes, our system is the only hUC-MSC commercially available with a clear line of sight to clinical translation.  Additionally, other suppliers (a) provide low cell number vials at a high price per M cells, (b) supply serum-based cells, or (c) require specialized, non-scalable culture vessels.  Finally, RoosterBio provides first in class characterization of hMSC key quality attributes (PDL, identity, expansion potential) and functional assays (cytokine secretion, trilineage differentiation, immunomodulation).

August 16, 2019

Behind Our Best Places to Work Award: Life Inside The Roost


We’re thrilled to share that we’ve been named a Frederick County Best Places to Work! This award is especially meaningful to us because our company was built with culture in mind, from our workspaces, our employee benefits, to the way we interact with our customers. 

What Makes RoosterBio a “Best Place to Work”

The Frederick County Best Places to Work is an annual campaign that showcases a company’s best practices to create an amazing place to work. The survey includes several open-ended questions centered around key components that help determine a winner. While an emphasis is placed on average median salaries and voluntary turnover rates, we wanted to share some of the key parts of our company’s culture that address other aspects of the award criteria. At RoosterBio, we’re serious about the work we do but we try not to take ourselves too seriously, and we have a little fun along the way!

Take a peek inside life at The Roost.


Attracting the Best Talent

RoosterBio is a pioneer at the forefront of a groundbreaking regenerative medicine industry with cutting-edge technology and science that attracts the brightest people from a variety of backgrounds. Employee equity in the company where everyone is a shareholder, a collaborative work environment with an open floor plan, community meeting spaces as well as a modern, open and airy laboratory space to work in - are all perks of being a Rooster.

We regularly host higher education students from across the country who are looking to further their experience in the lab, from Harvard University to the University of Virginia this year, this kind of partnership helps spread the word among academia about the kind of innovative work RoosterBio is doing. 

One of the partners we work with is the National Institute for Innovation in Manufacturing Biopharmaceuticals (NIIMBL) and the National Society of Black Engineers. This NIIMBL experience includes a tour and panel discussion to give students enrolled at historically black colleges and universities (HBCUs) an understanding of the kinds of careers available within biopharmaceutical manufacturing.

Retaining a Strong Workforce

Retaining our workforce is so critical that Building and Nurturing Company Culture is one of RoosterBio’s corporate and strategic objectives. It’s not just something on a piece of paper, but something we nurture and invest in every day.

The leadership team at RoosterBio believes in providing ongoing access to training and promotes transparency so much so that there is no question off-limits during our quarterly “All-Hands” Meetings. Our employees are highly engaged as measured by ongoing and anonymous surveys.


Cool Perks

RoosterBio’s workplace was built with Company Culture in mind, from glass doors on offices to promote openness, a collaborative community room to a fully-stocked kitchen that serves as the gathering spot for social events. Flexible work schedules, unlimited paid time off, a robust benefits package, access to things like financial advisors, travel planning discounts, discounted gym memberships, discounted child care and car buying discounts. In addition to 10 paid company holidays, and a floating holiday, we often shut down before holidays that isn’t a part of the communicated holiday calendar.

Promoting Fun at Work

Fun at work matters at RoosterBio because people work harder, stay longer and take better care of the organization when they’re not stressed out. The RoosterBio Culture Club plans events in five main areas: Onsite Fun, Offsite Fun, Volunteering/ Community Outreach, Employee Recognition and Health/Wellness with the mission to Make Work Awesome. We’ve celebrated everything from Take Your Child to Work Day and major holidays to things like International Haiku Day and National Scrabble Day. We recently held the 1st Annual RoosterGames at the RoosterBio Company Picnic where we put our teamwork and perseverance to the ultimate test! To relieve stress at the end of the day, you might hear the faint sound of a ping-pong ball in the distance or catch a group of Roosters at an after-hours happy hour.


Celebrating Success Together

Individual efforts are important but it’s team work that makes the dream work within The Roost. The Golden Rooster awards are for those employees who exemplify company values. These awards are nominated by fellow team members and given quarterly at “All Hands” meetings. Bonuses, additional company equity and work-sponsored celebrations are all ways that success is shared.

Not Just Culture Cluck

We are proud of what we’ve achieved together and it’s a great time to be a Rooster with even more exciting opportunities ahead. Check out our Introducing Our #Roosters campaign on LinkedIn and Facebook for testimonials from almost half of the company on what they decided to join RoosterBio. 

Check out our open positions as we expand our presence across the globe and be a part of this exciting journey.

July 15, 2019

Advances in Clinical Translation and Scale-up of MSCs and Extracellular Vesicles at ISCT 2019

Authored by Katrina Adlerz, Ph.D., Scientist, Analytics, Product & Process Development
& Josephine Lembong, Ph.D., Scientist, Analytics, Product & Process Development

The 2019 International Society for Cell and Gene Therapy (ISCT) Annual Meeting brought clinicians, regulators, and industry to Melbourne, Australia to collaborate and share progress in the rapidly developing field of Cell & Gene Therapy. Mesenchymal Stem/Stromal Cells (MSCs) were a major focus of the conference with an entire preconference workshop devoted to the Global Clinical Trial Landscape of MSCs as well as multiple sessions and keynotes throughout the conference. RoosterBio was active in the technical sessions and presented new technology on the industrial scale up of both MSCs and MSC-derived extracellular vesicles, as well as announcing a partnership with Tissue Regeneration Therapeutics to make umbilical cord -derived MSCs broadly available. Other key themes at this year’s meeting were: addressing global regulatory compliance, scalability, reducing cost of goods, exciting developments in exosomes/extracellular vesicles and recent advances in many different cell and gene therapy strategies.

MSC Progress in Clinical Trials, Manufacturing, and Comparability

Progress in clinical trials across the globe was the focus of a full day pre-conference workshop. Dr. Robert Mays of Athersys provided an update on their stromal cell product Multistem as they move into Phase III clinical trials for ischemic stroke patients and continue to investigate the treatment’s mechanism of action with immune regulation possibly being one key piece. Dr. Yufang Shi echoed this, highlighting work to pre-condition MSCs to bolster immune responses. Dr. Eleuterio Lombardo of Takeda discussed the development of Alofisel, an allogeneic MSC product that has been approved in Europe for perianal fistulas in Crohn’s disease. Some challenges in clinical trials were highlight
Photo courtesy http://www.isct2019.com/photo-gallery/
ed, such as inconsistent responses between pre-clinical and clinical studies. Dr. Lombardo pointed out an often-stated public opinion that successes in animal studies are often attributed to the use of “fresher” cells, and that these results may not be repeatable in human clinical trials because clinical trials often use cells that have been expanded and cryopreserved. Dr. Lombardo presented his review of the literature which did not support this opinion. Instead, he found that many studies did not state whether MSCs were cryopreserved or fresh, and surprisingly, it was also very rare that studies reported the Population Doubling Level (PDL). Furthermore, in his recent study where fresh and cryopreserved cells were

June 11, 2019

Cells as Bioinks for 3D Bioprinting

Authored by Mayasari Lim, PhD, Regional Account Manager, West Coast, RoosterBio

Bioprinting overview

The field of 3D bioprinting has exploded in recent years largely due to the advances in additive manufacturing technology along with progress in material chemistry and tissue engineering techniques. The key ingredients that make up the complex bioprinted structures are comprised of hydrogel-based biomaterial/s often coined as ‘bioinks’ and a cellular component that serves as building blocks to create a 3D printed biological tissue. Clearly, the choice of the cell source, proteins and other biological ingredients depends largely on the desired final application. For the purpose of this blog, we will only focus on the desire to create bioprinted tissue for clinical translation.

Which cell should I use?

Cells for clinical use can be derived from the patient (autologous) or a donor (allogeneic). In many tissue engineering applications, stem cells are used due to their properties in self-renewal and differentiation. Adult stem cells, currently being the most clinically viable solution, include hematopoietic, mesenchymal, neural and epithelial. While hematopoietic stem cell transplantation is widespread, it has limited utility in tissue engineering applications due to its limited differentiation capabilities primarily toward blood lineages. Neural stem cells are most effective in neural regeneration but the limited source makes it very challenging to become clinically relevant. Mesenchymal stem/stromal cells (MSCs), on the other hand, has a significant advantage due to its tri-lineage differentiation ability and immunomodulatory functions thus it has been widely used in various therapeutic indications including brain trauma, graft-versus-host disease and cardiovascular disease. Moreover, MSCs have already demonstrated clinical safety in > 800 clinical trials treating over 30,000 patients to-date.

How many cells do I need?

In order to print a 3D tissue, we need a significant number of cells seeded at a relatively high density to achieve full tissue mimicry. Exactly how many cells would one require? Let us take a look at a simple example of the knee meniscus. The figure below (left) illustrates a 3D model of an adult meniscus with rough dimensions of 3.5 cm in diameter and 5.3 mm in height. If we were to print this structure at 30% infill, it would require a total volume of ~2.5 mL of bioink. Several studies in bioprinting cartilage tissues have reported that cells would need to be seeded at high densities, a minimum of 10-25 million cells/mL in order to form cartilage in vivo[1, 2]. Thus, in this print, we would require roughly 62.5 million MSCs for a single print. For an intervertebral disc with a diameter of 4 cm and height of 10 mm (Figure on the right), the total volume of bioink required to perform a print would be 4 mL thus the total number of cells required would be 100 million for a single print. These two examples serve to illustrate the number of cells required to bioprint a simple 3D tissue. For larger tissues or organs, one can imagine that you will need a significantly higher number of cells, in the orders to 10 billion or more, to achieve desirable cell distribution through the tissue.


Traditional methods of expanding MSCs in the lab using 2D tissue culture flasks will require significant amount of time (weeks) and labor to obtain enough cell numbers given that most commercially available MSC vials are sold in 0.5-1 million cells/vial. Fortunately, RoosterBio has developed a ready-to-print cell vial (RoosterRTP™) with 50 million cells in each vial that significantly reduces and/or eliminates the need for growing cells in the lab so that researchers in the field of tissue engineering and bioprinting can focus on their research rather than worry about optimizing their expansion protocols. At the development stage, this would significantly reduce the amount of time for researchers to conduct multiple experiments thus generating more data in a shorter time. To scale such a process for commercial production, it would be necessary to estimate the required manufacturing lot size as described in our previous blog to build an effective multi-year process development program. In the case of the knee meniscus, there are over 700,000 patients requiring meniscus surgery in the US alone. To supply even 20% of this requirement, one would require 140,000 bioprinted knee meniscus which would be equivalent to 8.75 trillion cells annually.

References:

1. Cohen et al., 2018. Tissue engineering the human auricle by auricular chondrocyte-mesenchymal stem cell co-implantation. PLoSOne13(10): e0202356. doi: 10.1371/journal.pone.0202356

2. Moller et al., 2017. In vivochondrogenesis in 3D bioprinted human cell-laden hydrogel constructs. Plast Reconstr Surg Glob Open. 5(2): e1227. Doi: 10.1097/GOX.000000000000127