Injectable and stretchable biomaterials for improved tissue regeneration

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Last week, Nature dedicated an technology editorial to new advances in tissue engineering, more specifically the “organs-grown-in-a-lab” sub-field. Titled Tissue engineering: Organs from the lab, the article proclaimed, “Engineered tissues are starting to allow incisive experiments and even replacement therapies,” before concluding that new discoveries and advancements in tissue engineering not only offer a “better understanding of the basis of disease” but also a real potential to “cure those diseases.”

This comes on the heels of some remarkable new developments. MIT associate professor of mechanical engineering Xuanhe Zhao and colleagues at MIT, Duke University, and Columbia University described, in the journal Advanced Materials, the development of new hydrogels that are not only tough, but soft and “stretchable,” which can be assembled with approaches that do not require harsh chemicals. Not only that, but the hydrogels can be assembled into a variety of 3D structures by 3D printing, which opens up possibilities of their use as cell delivery carriers as well as scaffolds for expansion of stem cells. Indeed, the new materials are benign enough to synthesize together with living cells, such as stem cells. The authors are currently focused on improving the resolution of the printer, which is currently limited to details about 500 micrometers in size.

This comes in addition to a new paper, published in Nature Materials, from Dr. Dino di Carlo’s lab at UCLA, which describes a new injectable polymer gel for the rapid treatment of wounds.

The gel uses a cluster of microscopic synthetic polymer spheres, which produces MAP (microporous annealed particles) gel, which fills the wound and facilitates the growth of new tissue. Eventually the body degrades the spheres, leaving just the newly grown tissue. Cells are encouraged to migrate into the microporous gel and proliferate, and in doing so, encourage the assembly of new tissue.

New biomaterials will be they key to achieving biocompatible and effective tissue replacement and regeneration, and advances such as these are at the forefront of systems development toward effective biomedical therapies in regenerative medicine.

 

 

 

Encapsulation for Cell Cryopreservation: New Studies

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Improving cryopreservations strategies and developing optimal formulations of cryoprotectants is a high priority for the cell therapy and medical fields. A recent study from the Royal Free Hospital in London, UK investigated the toxicity associated with the exposure of cord blood samples to DMSO. The authors carried out cell viability and in vitro functional assays in fresh and post-thaw cord blood samples, and determined that the optimal concentration of DMSO for cryopreserved cord blood is in the 7.5 – 10% range, while the maximum exposure time should be limited to <1 h prior to freezing and 30 min post-thaw.

Elsewhere, new strategies for cryopreservation have appeared. The lab of Francisco del Monte at the Materials Science Institute of Madrid described the development, in the journal ACS Applied Materials and Interfaces, of liquid marbles encapsulating fibroblasts that are used for cryopreserving the encapsulated cells. Liquid marbles are spherical constructs – they are typically described as droplets – made of polymeric materials surrounding an aqueous core. They have been used for many applications. In the paper, the authors encapsulated murine L929 fibroblasts inside liquid marbles made up of poly(tetrafluoroethylene) and found that the cells were well cryopreserved in such a construct adhesion, morphology, viability, proliferation, and cell cycle. More studies are needed to further understand and optimize the utility of such processes, but this is one of the earliest examples of such a system.

Encapsulation was also employed in a new study on cryopreservation by a Jose Luis Pedraz’ lab at the University of the Basque Country in Spain. The authors tested a number of cryoprotectant solutions combining DMSO, glycerol and trehalose on encapsulated mesenchymal stem cells genetically modified to secrete erythropoeitin. Cells were encapsulated in multi-cell particles and were cryopreserved either with DMSO, glycerol or trehalose alone or a combination of cryoprotectants. The authors found that DMSO at a concentration of 10% displayed the best viability and erythropoietin secretion profile compared to the other cryoprotectant solutions. This is not, however, meant to exclude other compositions as being suitable for further development and optimization, considering the nature of this study was limited.

Some of these studies highlight that encapsulation, but more generally, novel approaches for cryopreservation, may hold keys to new solutions for the protection of hard-to-preserve cells for clinical use.

For more information about solutions for cryopreservation using DMSO as well as novel DMSO-free approaches, get in touch with us.

Cancer Immunotheraphies Heat Up: CAR T, Checkpoint Inhibitors and beyond

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This week, Merck and Dynavax announced a collaboration to study cancer immunotherapies based on a combination of Dynavax’s toll-like receptor 9 (TLR9) agonist candidate SD-101 with Merck’s Keytuda® (pembrolizumab), and, in a separate investigation, anti-interleukin-10 (anti-IL-10) immunomodulator MK-1966.

Elsewhere this week, OncoSec Medical debuted on NASDAQ, based on strong pre-clinical data on their upcoming clinical trials to treat triple breast cancer. This followed the announcement of a Sponsored Research Agreement (SRA) with Massachusetts General Hospital, to study the immunologic mechanisms underlying the anti-tumor effects of OncoSec’s clinical stage platform, ImmunoPulseTMIL-12. The platform is based on the introduction of DNA-based Interleukin-12 into subjects.

Also this week, Amgen and Kite Pharma announced a joint collaboration to develop and commercialize what they termed “the next generation” of Chimeric Antigen Receptor (CAR) T cell immunotherapies, following positive positive results from a Phase I/IIa trial, showing that eight of 13 patients with advanced B cell malignancies had complete remissions after receiving anti-CD19 CAR T cells.

These are just some of the more high profile recent examples of cancer immunotherapy treatments showing promising advances through clinical stages. Such immunotherapies are poised for exponential growth in the coming decade, if the recent market reports are anything to go by. Small biotechs, as well as large pharmaceuticals, are aggressively penetrating this market and adopting new technologies with high hopes for return. Novartis, having heavily invested in the CAR T cell therapy market so far, is expected to join competitors Bristol-Myers Squibb, Merck, Roche and AstraZeneca in developing checkpoint inhibitor drugs. These drugs are expected to lead the cancer immunotherapy market to multi-billion dollar status in the next decade.

Checkpoint inhibitor drugs were heavily featured at the American Society of Clinical Oncology annual meeting earlier this month, where multiple trials were presented showing a large amount of positive data based on checkpoint inhibitor-based treatments. More on some of these treatments is here.

Apart from positive effects when used individually, industry sentiments – and pre-clinical data – appear to favor combination strategies as having better efficacy outcomes than single-agent approaches.

Akron Biotech is the premier provider of several key raw materials for cell therapy. We provide small and established biotech and pharma clients with regulated raw materials for all stages of clinical development. Contact us with your manufacturing needs.

 

Meet Akron at ARM’S Science & Technology Committee Workshop on Cell & Gene Therapy Standards

This week, Akron Biotech will attaned the Alliance of Regenerative Medicine’s workshop Science & Technology Committee Workshop on Cell & Gene Therapy Standards, to be held Monday June 15 at University of Pennsylvania in Philadelphia, PA. For more information including agenda details, see here.

 

ISSCR Annual Meeting

Akron will attend the ISSCR Annual Meeting to be held in Stockholm, Sweden from 24-27 June, 2015. To schedule an individual meeting, contact us at info@akronbiotech.com.

 

 

 

 

FDA Guidances for Biological and Cell Therapy Products Seek To Bring Clarity to Drug Manufacturing

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This week, Business Insider called the the stem cell industry in the USA the “Wild West”, referring to the flurry of stem cell clinics (over 170 of them) currently operating throughout the USA, most of which with little or no government oversight.

These clinics have fluorished for a while, and while the FDA has not taken any formal action, it has began addressing loopholes that have allowed them to operating, one of which is a draft guidance released in December 2014 addressing the fact that the stromal vascular fraction, isolated from adipose tissue and containing adipose-derived stem cells, which is then used as a cell therapy product, is generally considered “more than minimally manipulated”, essentially sending the message that these clinics might have to go through formal FDA approval processes in the future.

Mushrooming stem cell clinics were not the only ones targeted by recent FDA guidances.

Last month, the FDA Issued a guidance, “Quality Considerations in Demonstrating Biosimilarity of a Therapeutic Product to a Reference Product,” wherein the agency calls for developers to provide clear clinical demonstration that a certain product is similar to a claimed reference product. This includes same biological and physical performance, including concentration and volume if the product is injectable.

And as recently as last week, the FDA issues a guidance, “Mixing, Diluting, or Repackaging Biological Products Outside the Scope of an Approved Biologics License Application; Draft Guidance for Industry,” which outlines conditions under which the FDA will not take action against outsourcing facilities engaged in mixing, diluting, or repackaging of biological products. It also highlighted that none of these activities are allowed for any cell therapy product outside of its BLA.

Finally, just this week the FDA issues a new guidance, titled “Established Conditions: Reportable CMC Changes for Approved Drug and Biologic Products,” which focuses on changes made to chemistry, manufacturing and controls of biological products. Essentially, it seeks to clarify what “established conditions” are and when a manufacturer must report changes made to the production of a product. You canr ead the guidance here.

By the issuance of these guidances, the FDA is seeking to bring more clarity to the manufacturing of biological, chemical and cell therapy products, and it’s refreshing to see the agency responding to industry calls for such guidances. While they are not perfect (critics have reported many drawbacks to some of the recent guidances), they are a first step.

 

Akron Participates at Standardization Workshops

Akron’s efforts at contributing to the cell therapy field by being involved in standardization efforts have been one our top priorities. As a committee member of the Alliance of Regenerative Medicine, we are closely involved with regulatory efforts aimed at legislative changes for better industry standards.

This week and next week, Akron will participate at two related events focusing on advancing efforts at supporting standardization in the cell therapy field.

You can meet Akron at:

Click the links above for more information.

Akron Biotech and Cognate BioServices Announce Strategic Partnership

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Cognate BioServices, Inc. and Akron Biotechnology, LLC are pleased to announce a strategic partnership that brings two industry leaders together to provide a more complete package of services to their clients. Cognate is a leader in the provision of cGMP manufacturing services and regulatory support to companies and institutions engaged in the development of regenerative medicine and cell-based products and therapies. Akron Biotech is an innovative supplier of validated reagents, solutions and technologies to the cell therapy industry. Their relationship strengthens both companies and will unify their resources to better serve growing market demands internationally.

Akron Biotech founder and CEO Claudia Zylberberg, PhD, stated, “This partnership is a unique opportunity to integrate the offerings of our two companies to meet the growing needs of the industry by strategically reducing the cost of goods through enabling solutions and procurement of raw materials in a cost-efficient manner for our customers and Cognate clients.”

J. Kelly Ganjei, CEO of Cognate BioServices, added, “We believe that offering a more full service integration with specific key supply chain demands provides us and our clients a competitive advantage in this field. Dr. Zylberberg and her team have built a brand around quality and innovation, two attributes that Cognate requires of itself internally. We are very excited about continuing to expand our collective offerings to our clients in the US and internationally.”

The companies will continue to operate as separate entities, with each company focusing on further developing its core competencies while contemporaneously leveraging each other’s strengths to advance new cell therapy-based treatments from workbench to the clinic. For Cognate’s core, these competencies include cGMP manufacturing, scale up, validation and process development through specialized infrastructure and expertise to support clients through all aspects of cell-based drug development up to and including commercialization. Akron’s core competencies include the production and distribution of validated raw materials and solutions to cell therapy clients, as well as innovating new products and technologies for the regenerative medicine space.

Akron Biotech’ Innovative Products and Services at ISCT

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Our recent expansion to a new state-of-the-art facility has allowed us to further expand our R&D efforts as well as provide improved support services to clients seeking validated cell therapy development processes – from bioassay development through product development, validated raw materials and scale up.

With new innovative products and solutions, we will be attending the ISCT Annual Meeting in Las vegas this week presenting the latest developments and offerings from Akron.

Highlights include:

  • Human Plasma Fibronectin: On the heels of one of the most-trusted fibronectin products on the market – our research grade fibronectin – we will be announcing the launch of our GMP-grade fibronectin, including the industry-first virus-inactivated GMP fibronectin. We will be presenting the various formulation options as well as custom delivery solutions including coating services and well as bioassay services with a variety of cell lines.
  • DMSO-Free Cyropreservation: Akron’s line of DMSO-free cryopreservation media, CryoNovo, is an ever-expanding line of cryopreservation media that is being developed under the mantra “one size doesn’t fit all.” In the spirit of this, we will be on hand to discuss options for cryopreserving traditionally hard-to-preserve cells as well as new developments in DMSO-free crypreservaton that address known difficulties encountered with various cell lines.
  • AB Serum: Akron’s AB serum is true off-the clot: visit us at our booth to learn how our superior AB serum product can help you in your cell culture projects where other AB sera have failed.
  • Custom Development Services: Bioassay development, cell therapy projuct validation, raw materials: innovations at Akron are constantly ongoing. Come to booth 412 to learn much more about how Akron is leading the way.

 

ISCT Agenda

Here is a breakdown of opportunities to meet us and hear from us:

  • Booth 412: We will be there throughout the conference, so make sure to come and speak with us
  • Poster 259: Come learn about the latest in DMSO-free cryopreservation media. The poster session is Friday, May 29th from 5:30 – 7 pm
  • Panel: Strategies for Commercialization Track 2 – Ancillary Materials. Dr. Claudia Zylberberg will chair, alongside Lynn Csontos, a panel discussion on ancillary materials on Thursday, May 28th from 11:15 – 12:30 in the Pompeian Ballroom I/II.
  • Talk: Critical Considerations for the Development of Cell Therapy Potency Assays. Case study: Angiogenesis. Dr. Claudia Zylberberg will speak on Thursday, May 28 during the Strategies for Commercialization Track from 4 –  5:30 pm in the Pompeian Ballroom I/II.

If you would like to set up a private meeting, please contact us at info@akronbiotech.com.

Akron Participates in NIST Standardization Workshop + Visit Us At ISCT

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Akron Moderates Potency Assay Standardization Workshop Akron last week participated in the workshop “Measurement Assurance for Cell Therapy Products,” held at and organized by the National Institute of Standards and Technology. The workshop brought together some of the leading representatives from industry and academia to discuss the best strategies for the standardization of various measurements critical in the development of cell therapy products: cell counting, cell viability and potency assays. A series of seminars gave way to the workshop sessions, which saw the participants split into three groups, each tackling one of the three critical measurement areas. Discussions ranged from challenges currently experienced when dealing with various assays (such as cell clumping during cell counting), to best cross-labroatory solutions how to address and solve these problems. Akron’s Dr. Sandro Matosevic was a moderator at the session on Potency Assay development, alongside Dr. Juliana Woda (Juventas), Dr. Yael Porat (Biogencell), Dr. Eytan Abraham (Lonza) and Dr. Carl Simon (NIST), which was also organized by Akron’s Dr. Claudia Zylberberg. The session focused on two angiogenesis potency assays: endothelial cell proliferation and the tube formation assay, both of which were identified as suffering form significant drawbacks stemming from the multiple factors involved in their setup, particularly the tube formation assay. Some of these include variability in cell source, tube-inducing growth factor as well as detection which is very subjective and relies on processing of microscope-collected images. Potential solutions for standardization were proposed, as well as strategies to achieve harmonization across the various elements of the assays. The two-day workshop highlighted the critical need for industry and academia to work together on identifying best practices – as well as bottlenecks – during the cell therapy product development process, as well as industry-wide organizations’ role in bridging such gaps. Further follow-ups from the workshop will outline some of the proposed solutions. Akron at ISCT in Las Vegas This year, Akron will again participate at the International Society of Cell Therapy Annual Meeting. In the interest of efficiency, here is a breakdown of opportunities to meet us and hear from us:

  • Booth 412: We will be there throughout the conference, so make sure to come and speak with us
  • Poster 259: Come learn about the latest in DMSO-free cryopreservation media. The poster session is Friday, May 29th from 5:30 – 7 pm
  • Talk: Critical Considerations for the Development of Cell Therapy Potency Assays. Case study: Angiogenesis. Dr. Claudia Zylberberg will speak on Thursday, May 28 during the Strategies for Commercialization Track from 4 –  5:30 pm in the Pompeian Ballroom I/II.
  • Panel: Strategies for Commercialization Track 2 – Ancillary Materials. Dr. Claudia Zylberberg will chair, alongside Lynn Csontos, a panel discussion on ancillary materials on Thursday, May 28th from 11:15 – 12:30 in the Pompeian Ballroom I/II.

If you would like to set up a private meeting, please contact us at info@akronbiotech.com.