June 29, 2020 by admin 0 Comments

Bioprinted Skin Patches for Diabetic Foot Ulcers Commercialized by Rokit Healthcare

After years of investigating ways to manage treatment for diabetic foot ulcers (DFU), Korean 3D bioprinter manufacturer, Rokit Healthcare finally announced the success of a new DFU regeneration platform based on its 4D bioprinting technology for customized tissue regeneration. This new and alternative method for chronic wound healing promotes a mechanism of skin reconstruction for DFU treatment that was successfully tested on patients and will be globally commercialized this year.

To find an advanced treatment method, particularly for wound healing, Rokit tested the DFU therapy with its own 4D bioprinting system, using a personalized bioink developed with the patient’s own adipose tissue that had no immune rejection.

With diabetes on the rise in most countries, patients require targeted therapies and effective solutions for pain management. Today, over 460 million adults have diabetes, that’s roughly 6% of the global population, and it is expected to reach 700 million patients by 2045. Furthermore, diabetes can damage eyes, kidneys, and nerves, cause heart disease, stroke, and even the need to remove a limb. In fact, diabetic foot ulcerations are one of the most common complications associated with diabetes, as an estimated 50% of diabetic ulcers become infected and could result in amputation.

Rokit’s mission is to decrease the rate of amputation for patients with DFU, by offering safe and effective regenerative therapy based on 4D bioprinting technology. As part of one of their continuing studies, a global Rokit team successfully tested its DFU regeneration platform on patients in India and will continue clinical trials in South Korea, Europe, North America, and East Asia.

The process begins with fat tissue taken from a patient (for example through liposuction), which is then used to prepare an autologous extracellular matrix (ECM) mixture to form a bioink that is loaded into Rokit’s INVIVO 4D bioprinter to produce a dermal patch. The autologous patch is finally implanted at the wound site after the damaged tissue has been removed.

The results of the study, published in the American Diabetes Association‘s journal Diabetes, describe how the autologous ECM patch, applied onto the chronic wound site of DFU patients, resulted in a significant wound size reduction after only a one-time treatment.

During the tests, most of the patients showed complete closure of the wound in only two to five weeks. In fact, after a 14-day skin wound healing process, the treated wound area had more effectively reconstructed epidermal and dermal structures when compared to the non-treated wound areas.

▲ After the process, the treated wound area has more effective reconstructed epidermal and dermal structure compared to the non-treated area (Credit: Rokit Healthcare)

“My team recently focused on skin regeneration, especially for caring diabetic foot ulcers. Using our 4D bioprinting system with patient’s autologous fat tissue, diabetic foot ulcers were successfully healed after getting only one treatment during the clinical trials. Rokit’s DFU regeneration platform will provide a safe, fast, and cost-effective solution for curing diabetic wounds,” said Jeehee Kim, president of Rokit Healthcare’s DFU and Skin Regeneration Strategy Business Unit and author of the published paper.

Currently, diabetic foot ulcers are treated with dressings, negative pressure, and skin grafting, but according to Rokit, these treatments have proven ineffective, costly, and time-consuming for patients, moreover, they do not provide the correct therapeutic approach as regenerative medicine and tissue engineering would. Instead, the company’s alternative treatment solution to promote skin reconstruction, along with its use of biomaterials and bioink designs, can hold a lot of promise for future effective customized 4D bioprinting to regenerate human tissues and organs.

▲ DFU treatment process (Credit: Rokit Healthcare)

To find an advanced medical solution, particularly for diabetic wound healing and skin regeneration, Rokit used its 4D bioprinting platform along with the minimally manipulated autologous fat tissue. According to the company, INVIVO was key to its success, provided a fast regeneration effect and customized treatment that fits the skin loss area.

“Dr. INVIVO is what we believe to be a scientific breakthrough. It’s the world’s first clean bench hybrid 4D bioprinter. When creating a regenerative patch on diabetic foot ulcer patients, Dr. INVIVO plays a mayor role. With its precise and rapid manufacturing capabilities, Dr. INVIVO helps create a personalized therapy solution by building patient specific designs,” explained one of Rokit Healthcare’s R&D engineers, Jaeyong Shin One.

As reported by MK’s Maeil Business Newspaper, Rokit Healthcare has begun commercializing in 48 countries its DFU treatment platform that uses 4D bioprinter Dr. INVIVO. To that end, the company signed a per region export business cooperation agreement and expects the number of sales for this year alone to reach 424 million dollars and well over one billion dollars by 2022. For now, the contract enables commercialization of the platform to India, countries in Europe, Latin America, the Middle East, and North Africa. However, the company already has plans to expand, launching the platform in other regions, like North America, Japan, China, and Australia.

The platform includes all of the procedures required to treat DFU, including 3D scanning of the affected area, diagnosis, bioprinting with personalized bioinks, and a procedure kit. In addition to domestic patents, the company has obtained certifications from the European Medicines Agency (EMA) and is currently undergoing the required procedures from the Food and Drug Administration (FDA) that would allow commercialization in the United States.

The company’s INVIVO bioprinting technology has already been acquired by research labs and institutions in more than 25 countries, specializing in tissue and material engineering, drug testing, 3D tissue, and disease modeling. Dr.INVIVO is the world’s first sterile, all-in-one 4D organ regenerator. Rokit’s autologous skin regeneration procedure using Dr.INVIVO already received regulatory approval for non-advanced therapy medicinal products (ATMP) by the EMA for the treatment of diabetic ulcers, pressure ulcers, scar revision, and burn wounds, meaning immediate access to the operating room.

▲ Dr. INVIVO (Credit: Rokit Healthcare)

“Imagine that you get a 3D bioprinting service in a hospital to renew your damaged body parts. The human body is composed of cells, proteins and extracellular materials that we can also use a bioink to regenerate organs, which means regrowing the injured body back to its original shape and function,” Kim went on. “4D bioprinting technology is the best method to create human organs, such as skin, cartilage and bone tissue. We live in the era of the fourth industrial revolution that will ideally change human lifestyle, including our healthcare service. Now, Rokit Healthcare leads the advanced cutting edge 4D bioprinting technology as a pioneer.”

Ulcer healing usually takes weeks or even months, with many ulcers never healing and resulting in amputations. By promoting mechanisms of skin reconstruction, this alternative method could be essential to reducing the risks associated with DFU’s, as well as help lower therapy costs, and lead to a better quality of life for patients. By attempting to cure the inevitable development of diabetic ulcers, Rokit Healthcare is pioneering the foot regeneration treatment market thanks to its innovative development. However, healing diabetic ulcers is only the beginning, the company’s unique treatment platform is already moving into cartilage regeneration and other skin wounds and disease.

June 25, 2020 by admin 0 Comments

ROKIT Healthcare Reveals World’s First All-in-One Bioprinting Platform with Built-in Bioreactor Chamber, Plasma Sterilizer and 6 Rotary Printheads: Dr. INVIVO 4D6

ROKIT Healthcare announced the launch of the Dr. INVIVO 4D6, a bioreactor-based bioprinting platform with a built-in cell incubator and low-temperature plasma sterilizer as the first of its kind. It is designed and built with the vision of in-hospital manufacturing and offers a controlled cellular environment in aseptic conditions in combination with the complex biofabrication technologies of six rotary printheads. ROKIT Healthcare is a South Korea-based regenerative medicine solutions company that develops hardware, software, and clinical application platforms employing 4D bioprinting technology for customized human organ and tissue regeneration.

Chief Executive Officer at ROKIT Healthcare, Seok Hwan You, explains: “Bioprinting right by the bedside inside the operating theatre means minimized time, risks, and costs in the transfer of patient cells to the bioprinter and in the transfer of printed tissues back to the patient. It is a new kind of point-of-care, personalized healthcare solution that maximizes the benefits of autologous regenerative medicine technologies. Dr. INVIVO 4D6, which we call the Organ Regenerator, is designed to pave the way with features that have been added after feedback from physicians and scientists.”

Features on the Dr. INVIVO 4D6 from ROKIT Healthcare

Achieving three-dimensional architecture is just one of several factors to consider in tissue engineering. Cell environment factors, like incubation temperature, oxygen/carbon dioxide level, and humidity are key to successful human tissue and organ development with optimal cell viability and functionality. Moving beyond the capacity to dispense cells and biomaterials with multiple printheads, Dr. INVIVO 4D6 offers an integrated system to meet clinical needs in human tissue engineering and its translational applications.

Dr. INVIVO 4D6 optimizes tissue engineering and regenerative medicine research with:

  1. Built-in cell incubator with temperature, humidity and CO2 control
  2. 6 printheads for complex tissue fabrication with hydrogels, filaments, polymer pellets, and diverse FDA-approved materials
  3. Complete particle control with circular air flow generation technology, much like a biosafety cabinet
  4. High-throughput to the max with up to 384-well tissue screening and assay development

Translation of Bioprinting in the Operating Room

In addition to being a bioprinter manufacturer, ROKIT Healthcare works as a medical contractor that partners with state agencies, biotech firms and academic research centers to develop applications for bioprinting technology in the hospital operating room. ROKIT Healthcare has been awarded a $3 million grant by the South Korean government to co-develop an in-situ 3D bioprinting system for skin regeneration. Since 2019, ROKIT Healthcare has partnered with specialty plastic surgery hospitals around the world to offer 3D scan-print skin regeneration platforms for patients suffering from chronic diabetic foot ulcers and burns. The company has completed clinical studies in India and Korea.

Founded in 2012 and active in more than 50 countries, the company is advancing the scientific and healthcare revolution in regenerative medicine by providing on-demand human tissue manufacturing solutions in vivo and in vitro.

What do you think of the Dr. INVIVO 4D6 from ROKIT Healthcare? Let us know in a comment below or on our Facebook and Twitter pages! Sign up for our free weekly Newsletter, all the latest news in 3D printing straight to your inbox!

May 29, 2020 by admin 0 Comments

3D-Bioprinted Aptamer-Functionalized Bio-inks for Spatiotemporally Controlled Growth Factor Delivery

Authors
Deepti Rana, Vasileios D. Trikalitis (Contributor), Vincent R. Rangel (Contributor), Ajoy Kumar Kandar (Contributor), Nasim Salehi Nik (Contributor), Jeroen Rouwkema* (Contributor)
Abstract
Introduction Spatiotemporally controlled growth factors delivering systems are crucial for tissue engineering. However, most of the current strategies for growth factors delivery often focuses on the immobilization or coupling of growth factors within the engineered matrices (hydrogel) via various linker proteins or peptides. These systems provide passive release rates and growth factor delivery on demand, but fail to adapt their release rates in accordance with the tissue development. To overcome this limitation, the present study employed nucleic acid based aptamers for achieving spatiotemporally controlled growth factor delivery. Aptamers are affinity ligands selected from DNA/RNA libraries to recognize proteins with high affinity and specificity.1 Aptamer based growth factor delivery systems are able to load/release multiple growth factors on demand with high specificity. In the present study, the authors have 3D-bioprinted aptamer-functionalized bio-inks to evaluate their potential for growth factor sequestering, programmable release and for studying their effect on vascular network formation. Methods The aptamer-functionalized hydrogels were prepared via photo-polymerization of gelatin methacryloyl (GelMA) and acrydite functionalized aptamers having sequence specific for binding to vascular endothelial growth factor (VEGF165). Visible light photoinitiator, tris(2,2′-bipyridyl)dichloro-ruthenium(II) hexahydrate with sodium persulfate was used. The 3D-bioprinting experiments were carried out using Rokit Invivo 3D printer. The viscoelastic properties of the bio-inks were evaluated and compared with control GelMA bio-ink. To study the programmable growth factor release efficiency, VEGF antibody immunostaining was used. For studying the effect of triggered growth factor release on vascular network formation, human umbilical vein endothelial cells (HUVECs) and mesenchymal stem cells (MSCs) were encapsulated within the bio-inks. Results & Discussion The results obtained from VEGF antibody immunostainings confirmed the sequestration and triggered release of VEGF in response to complementary sequence addition from the 3D bioprinted construct after 5 days of culture. The bioprinted construct showed high cellular viability. The F-Actin/DAPI staining showed cellular sprouting and vascular network formation within the 3D printing aptamer functionalized bio-ink regions. In addition, the endothelial cells showed variations in cellular organization based on the VEGF bound aptamer availability within the bioprinted construct. These observations altogether confirms the bioactivity of VEGF bound aptamers within the printed constructs. Conclusions The present study shows the vasculogenic potential of 3D bioprinted aptamer-functionalized bio-inks via spatiotemporally controlling VEGF availability within the hydrogel system. Acknowledgements: This work is supported by an ERC Consolidator Grant under grant agreement no 724469. References 1. M.R. Battig, et. al., J. Am. Chem. Soc. 134 (2012) 12410-12413.

April 23, 2020 by admin 0 Comments

3D Bioprinted Vascularized Tumour for Drug Testing

Authors
Seokgyu Han 1, Sein Kim 2, Zhenzhong Chen 1, Hwa Kyoung Shin 3,4,5, Seo-Yeon Lee 6, Hyo Eun Moon 7,8, Sun Ha Paek 7,8 and Sungsu Park 1,2,9,10,*
Abstract
An in vitro screening system for anti-cancer drugs cannot exactly reflect the efficacy of drugs in vivo, without mimicking the tumour microenvironment (TME), which comprises cancer cells interacting with blood vessels and fibroblasts. Additionally, the tumour size should be controlled to obtain reliable and quantitative drug responses. Herein, we report a bioprinting method for recapitulating the TME with a controllable spheroid size. The TME was constructed by printing a blood vessel layer consisting of fibroblasts and endothelial cells in gelatine, alginate, and fibrinogen, followed by seeding multicellular tumour spheroids (MCTSs) of glioblastoma cells (U87 MG) onto the blood vessel layer. Under MCTSs, sprouts of blood vessels were generated and surrounding MCTSs thereby increasing the spheroid size. The combined treatment involving the anti-cancer drug temozolomide (TMZ) and the angiogenic inhibitor sunitinib was more effective than TMZ alone for MCTSs surrounded by blood vessels, which indicates the feasibility of the TME for in vitro testing of drug efficacy. These results suggest that the bioprinted vascularized tumour is highly useful for understanding tumour biology, as well as for in vitro drug testing.

February 14, 2020 by admin 0 Comments

Photocurable chitosan as bioink for cellularized therapies towards personalized scaffold architecture

Authors
Chiara Tonda-Turo (a) (b), Irene Carmagnola (a) (b), Annalisa Chiappone (b) (c), Zhaoxuan Feng (d), Gianluca Ciardelli (a) (b), Minna Hakkarainen (d), Marco Sangermano (b) (c)
Abstract
Recent progresses in tissue engineering are directed towards the development of technologies able to provide personalized scaffolds recreating the defect shape in a patient specific manner. To achieve this ambitious goal, 3D bioprinting can be combined with a suitable bioink, able to create a physiological milieu for cell growth. In this work, a novel chitosan-based hydrogel was developed combining photocrosslinking and thermo-sensitive properties. Commercial chitosan (CS) was first methacrylated and then mixed with β-glycerol phosphate salt (β-GP) to impart a thermally induced phase transition. The absence of cytotoxic degradation products and the excellent biocompatibility of the developed hydrogel was confirmed through in vitro tests using different cell lines (NIH/3T3, Saos-2, SH-SY5Y). Cellularized 3D structures were obtained though 3D bioprinting technologies confirming the processability of the developed hydrogels and its unique biological properties.

September 3, 2019 by admin 0 Comments

Interview with Seok-Hwan You of Rokit Healthcare on Bioprinting

When Seok-Hwan You founded Rokit Healthcare the company was one of the first worldwide to be able to 3D print PEEK and other high-performance materials. It quickly grew to dominate its local Korean medical and bioprinting market before reaching overseas for expansion. Recently the firm pivoted from just selling 3D printers and materials towards offering integrated solutions. With a renewed focus on regenerative healthcare, the firm is offering complete solutions for bioprinting. Rokit Healthcare now offers bioinks, the firm has a tissue bank, a 3D printing service and training. Rokit Healthcare is now furthering its goal to lead in bioprinting. I was very impressed by Rokit’s facilities and staff when I visited the firm. We interviewed Rokit Healthcare CEO Seok-Hwan You to find out more about his vision on bioprinting and goals for the pioneering company.

What is Rokit Healthcare?

ROKIT Healthcare strives to improve the quality of life and health around the world by addressing the problem of aging and age-related diseases with total, healthcare solutions. 3D biofabrication and the development of patient-specific tissue and organ regeneration therapies are our core capabilities. However, we are also involved in the provision of other healthcare programs, such as genetic testing of individuals, customized insurance services, and global medical tours.

Why did you pivot towards regenerative medicine and away from bioprinting?

We have not pivoted “away from bioprinting” per se. It is very much our core scientific technology; it sets the base for personalized therapy solutions we expect to introduce to global hospitals, from patient-specific skin and cartilage regeneration to heart and retina patch biofabrication solutions. However, as previously mentioned, we believe bioprinting must converge with other preventive medicine and diagnostic technologies, digitalization and healthcare management strategies to be truly effective at the level of patient outcomes.
So, we seek to address regenerative medicine and healthcare from a much wider vantage point, with bioprinting as an important but not the only one area of our endeavors.

Why should 3D Print partner with you?

What sets ROKIT Healthcare apart is that we offer services and insights from a total regenerative medicine solution provider’s perspective rather than a 3D bioprinting device, biomaterial, or 3D printed tissue products company.
As much as 3D bioprinting sits at the center of an exponential tech convergence, a group that can approach the field from various vantage points of health business and economics is likely to be an ideal partner for 3D Print in reaching out to its diverse professional client bases. ROKIT Healthcare is such a group.

What customers are you looking for?

Currently, our priority lies in developing customer bases for our 3D bioprinter and biomaterial platforms. Our focus customers include research groups from universities, government institutes, hospital labs, and pharmaceutical companies. The fields of application range from tissue engineering and regenerative medicine to micro-tissue development for pharmaceutical testing as an alternative to animal experiments. Soon, however, as we introduce 3D bioprinting-based therapy solutions like skin and cartilage regeneration platforms, we expect our client bases to expand beyond life sciences research to doctors and medical device companies.

What is your company culture like?

Like all great companies, we value integrity, excellence, respect, collaboration, and autonomy. But the four key values we as a company live by are: 1) ownership: we encourage strong ownership and autonomous decision-making by employees; 2) detail-orientation: we approach every task with a practice of thoroughly and concisely reviewing product or service execution; 3) no surrender: we do not give up easily and find value in even the littlest 1% possibility against 99% objections; 4) back to the basics: we stick to simplicity and adherence to fundamental principles and values of integrity, discipline, and respect.

At the convergence of these four values stands one key action principle: “Keep Blitz and Simple”. We, ROKIT Healthcare, are committed to maximizing employee freedom to fight the “python of process”. We give unusual amounts of freedom and information to all employees, sharing documents and business plans internally broadly and systematically, because we believe that highly-informed and autonomous employees are capable of good judgment to lead the company to success.

What do you hope to achieve over the next five years?

We envision integrating the 3D bioprinter and its applications into the traditional healthcare services, making the idea of bioprinting as a medical device a reality. Already we have begun the journey this month, with the start of our first clinical study of bioprinting-based skin regeneration for diabetic foot ulcer patients in India (August, 2019).

Why is it important to bioprint inside the operating theatre?

Bioprinting right by the bedside inside the operating theatre means minimized time, risks, and costs in the transfer of patient cells to the bioprinter and in the transfer of printed tissues back to the patient. It is a new kind of point-of-care personalized healthcare solution that maximizes the benefits of autologous regenerative medicine technologies.

What bioprinting materials are you excited about?

Nowadays, there are many kinds of bioinks in the market, including synthetic and natural polymers. But, they are not all applicable to the human body. We say “Aging is a Disease; Nature is the Best Therapy”. In that sense, we are excited about the whole extracellular matrix (ECM)-based bioinks that are derived from the ‘Human Body’. We believe the ECM is Nature.

What new developments are very interesting to you?

When it comes to traditional diagnostics of cancer, regardless of its kinds, doctors have been treating their patients only with bulk RNA-based analysis. But, as many of us realize today in the cancer research field, we know that the reason cancer is so hard to treat is that it is an extremely heterogeneous population of cells. We understand that each cell is its own universe. Understanding each of these universes is only possible by single-cell RNA analysis, and this will be key to taking any step closer to finding effective treatments for cancer. The scRNA technology may have much room to mature, but we’re working on it excited about its potential.

What products do you have?

We supply INVIVO, our signature 3D bioprinter. Plus, we supply 3D printers for material engineering and advanced prototyping in biomedical fields with materials like PEEK and ULTEM.

Do you have high hopes for PEEK? PCL? Other materials?

We have been paying a great deal of attention to broadening applications for medical-grade PCL and PEEK, especially in the applications of bone regenerative matrix and customized pill fabrication. However, the greatest focus of our energy lies not on synthetic plastics, but on natural ingredients like human ECM as a supportive materials for 3D printed living cells.

What are the challenges in bioprinting?

The biggest challenge that all industrial players of 3D bioprinting face is closing the gap between the technology we supply and the actual needs of our customers in the bioprinting research. A key part of these needs is to understand that bio 3D printing, unlike industrial 3D printing, is not only about manufacturing structures with architectural stability but about promoting cell ingrowth and considering the impact of manufacture on cell viability. Based on a constant probe into such understanding, we are building a base for developing next-generation bioprinting technologies and biomaterial applications.

August 30, 2019 by admin 0 Comments

Bioprinting Technologies in Tissue Engineering

Authors
Bengi Yilmaz, Aydin Tahmasebifar, Erkan Türker Baran
Abstract
Bioprinting technology is a strong tool in producing living functional tissues and organs from cells, biomaterial-based bioinks, and growth factors in computer-controlled platform. The aim of this chapter is to present recent progresses in bioprinting of nerve, skin, cardiac, bone, cartilage, skeletal muscle, and other soft tissues and highlight the challenges in these applications. Various composite bioinks with bioactive ceramic-based scaffolds having patient-specific design and controlled micro-architectures were used at clinical and preclinical applications successfully for regeneration of bone. In nerve tissue engineering, bioprinting of alginate- and gelatin-based gel bioinks by extrusion presented a controllable 3D microstructures and showed satisfactory cytocompatibility and axonal regeneration. Bioprinting of cardiac progenitors in biopolymers resulted in limited success, while the use of bioinks from extracellular matrix induced satisfactory results in cardiac regeneration. Osteochondral scaffold bioprinting is challenging due to the complex hierarchical structure and limited chondral regeneration. Therefore, current approaches focused on osteochondral scaffold with vascular network and mimicking hierarchical structures. The applications of bioprinting in other types of tissues were also studied, and results showed significant potentials in regeneration of tissues such as cornea, liver, and urinary bladder.

August 21, 2019 by admin 0 Comments

An interview with Heon Ju Lee on ROCKIT Healthcare’s novel bioprinting treatment for dermal scarring

Authors
Heon Ju Lee
Abstract
In this exclusive interview, Heon Ju Lee discusses ROCKIT healthcare’s novel bioprinting technique used to treat patients with dermal scarring. This interview was conducted by Mike Gregg, Commissioning Editor of the Journal of 3D Printing in Medicine.Dr Heon Ju Lee is the Chief Technology Officer and Managing Director of ROKIT. He is developing the service platform technology for artificial organ regeneration and supervises the overseas business development for the propagation of such service platforms. The focus of these platforms, bringing bio 3D print-based medical therapies into the operating room, on tissues that are relatively easy to fabricate structurally with the current technology, this includes skin, cartilage, hair, retina and heart patch regeneration. Dr Lee has a PhD from MIT in mechanical engineering and has been working as a 3D/4D printing group leader at KIST.

June 1, 2018 by admin 0 Comments

The Arrival of Commercial Bioprinters – Towards 3D Bioprinting Revolution!

Authors
Deepak Choudhury*, Shivesh Anand, May Win Naing*
Abstract
The dawn of commercial bioprinting is rapidly advancing the tissue engineering field. In the past few years, new bioprinting approaches as well as novel bioinks formulations have emerged, enabling biological research groups to demonstrate the use of such technology to fabricate functional and relevant tissue models. In recent years, several companies have launched bioprinters pushing for early adoption and democratisation of bioprinting. This article reviews the progress in commercial bioprinting since the inception, with a particular focus on the comparison of different available printing technologies and important features of the individual technologies as well as various existing applications. Various challenges and potential design considerations for next generations of bioprinters are also discussed.