February 22, 2019 by admin 0 Comments

Three-dimensional printing of wood-derived biopolymers towards biomedical applications

Authors
XU, Wenyang
Abstract
Three-dimensional (3D) printing has shown promising potential in fabrication of complex tissue with a structural control from micro- to macro-scale, meeting the requirements of tissue engineering. Wood-derived biopolymers as a category of biomaterials have attracted great attention as the feedstock materials in 3D printing owing to their abundant availability, biocompatibility, and in vitro biodegradability. However, the key issues are to tailor wood-derived biopolymers to 3D printable ink formulations and maintaining shape fidelity. The work of this thesis is dedicated to developing different types of ink formulations to be used in biomedical applications concerning the utilization of wood-derived biopolymers in a highly valuable and efficient way.<br /> Firstly, the O-acetyl-galactoglucomannan (GGM), a side-stream biopolymer from Norway spruce, was investigated for filament preparation with poly-lactic acid (PLA) in its native and bulk form. A solvent blending approach was established to blend GGM and PLA together for further PLA/GGM filament preparation. As much as 20% of the PLA could be replaced by GGM without decreasing the mechanical properties of the filament. 3D scaffolds were successfully printed from the polymer blends by fused deposition modeling 3D printing. The biocompatible and biodegradable feature of wood-derived hemicelluloses would potentially boost this new composite ink in various biomedical applications such as tissue engineering and controlled drug release.<br /> Cellulose nanofibrils (CNFs), a product of nanomaterials from cellulose, have been studied in formulating hydrogel inks owing to their intrinsic properties of the shear thinning behavior, structural similarity to extracellular matrix, and biocompatibility. The formulation of TEMPO-oxidized CNFs with gelatin methacrylate (GelMA) into low-concentration bioinks facilitated the crosslinking ability of GelMA (≤ 1 w/v %), and further enhanced the shape fidelity of the printed scaffolds. 3D printable low-concentration inks showed promising potential in tissue engineering due to the relative loose polymer network that can encourage cell-cell interaction, migration, and more efficient metabolism.<br /> GGM as a polysaccharide with abundant hydroxyl groups was chemically modified to be used as the cross-linker for CNF-based inks. Two derivatization approaches were established. In one approach, TEMPO-mediated oxidation was applied to introduce carboxylic groups, which were further reacted with tyramine to obtain tyramine-conjugated GGM. In the other approach, GGM methacrylate was synthesized in a facile and green process under aqueous condition. Both tyramine-conjugated GGM (GGMTA) and GGM methacrylate (GGMMA) were separately studied to successfully form gel by enzymatic and UV-aided cross-linking, respectively.<br /> Furthermore, surface-engineered biomimetic inks were formulated with GGMMA and CNFs thanks to the intrinsic affinity of GGM to cellulose fiber surfaces mimicking the plant cell wall. The formulated homogeneous inks facilitated the high-resolution printing of complex scaffolds and geometries. More importantly, the stiffness of the resulted hydrogels was tunable in a wide spectrum ranging from 2.5 to 22.5 kPa by controlling the degree of substitution of methacrylate and compositional ratio of CNFs and GGMMA. As a new family of 3D printing feedstock materials, the CNF/GGMMA inks will broaden the map of bioinks, which potentially meet the requirements for a variety of in vitro cell-matrix and cell-cell interaction studies in the context of tissue engineering, e.g. cancer cell research, and high-throughput drug screening.<br /> Lastly, the biocompatibility of the CNF-based bioinks was proven with incubating 3T3 fibroblast cells. The mechanical properties and topography of the printed scaffolds with CNF/GelMA inks could manipulate the cell attachment and promote cell proliferation. The developed low-concentration ink formulations with a facile yet effective approach to fabricate scaffolds show a great deal of potential in bioprinting for wound healing and soft tissue regeneration.

February 20, 2019 by admin 0 Comments

ROKIT Healthcare Announces a Novel Application of Dermal Regeneration Platform Using Proprietary Three-Dimensional Bioprinting Strategy

Applications of the treatment will expand to different indications in need to regenerative therapeutic strategies, including scar removal, burns, and pressure/diabetic foot ulcers– CISION PR Newswire

ROKIT Healthcare, Inc., a regenerative medicine company focused on the development of novel regenerative therapeutic strategies using three-dimensional (3D) biofabrication technologies for treatment of various medical conditions including dermatological, orthopedic, and autoimmune disorders, announced a novel application of dermal regeneration platform using autologous cells and its proprietary 3D bioprinter INVIVO®. This new regenerative therapeutic platform will be further studied in clinical settings for patients in need of treatment for damages suffered from dermal scarring.

Rokit Healthcare 3D Bio Printer INVIVO

Skin scarring is one of the most common medical conditions that can arise after almost every dermal injury, some of which can cause considerable physical, aesthetic, psychological and social problems that result in millions of elective operations and operations after trauma.

ROKIT’s treatment strategy uses INVIVO®, ROKIT’s proprietary 3D bioprinter, and patient’s autologous tissues and cells to “print” a dermal patch graft to treat scarred lesions. Combination of the 3D printing technology that allows for uniform and equal-density distribution of the cells and the use of patient’s autologous tissue/cells can lead to rapid migration of keratinocytes and neovascularization at the wound site, resulting in effective regeneration of the skin at treated lesion.

“It is a novel way of overcoming some of the most pronounced limitations associated with traditional stem cell therapy. The current practice of directly injecting expanded or cultured stem cells using syringes severely limits cell viability and accurate, uniformly distributed delivery of effective stem cells unto the disease area,” stated Seok-Hwan You, Chief Executive Officer of ROKIT Healthcare. “Utilizing 3D bioprinting techniques allows for effective delivery of autologous cells unto the wound site, minimizing cell loss and greatly enhancing cell viability and proliferation.”

ROKIT will further evaluate the effectiveness of the treatment in investigator-initiated clinical studies, which will initially open in Korea, with expansion to multiple countries worldwide. The company plans to expand the application of this novel treatment strategy to other dermatological conditions such as burns, pressure ulcers, and diabetic foot ulcers.

About ROKIT Healthcare, Inc.

ROKIT Healthcare, Inc. is a South Korea based regenerative medicine company headquartered in Seoul, South Korea, with satellite offices in Sulzbach, Germany and Boston, MA. The company is focused on the development and commercialization of personalized regenerative therapeutics using its proprietary 3D bioprinter INVIVO® and unique biofabrication strategies, for areas of high unmet medical need, including dermatological, orthopedic and autoimmune disorders. Additional information about ROKIT is available at www.rokithealthcare.com.

ROKIT Healthcare Forward-Looking Statement:

This press release contains certain forward-looking statements regarding, among other things, statements relating to goals, plans and projections regarding the Company’s financial position, results of operations, market position, product development and business strategy. Such forward-looking statements are based on current expectations and involve inherent risks and uncertainties, including factors that could delay, divert or change any of them, and could cause actual outcomes and results to differ materially from current expectations. No forward-looking statements can be guaranteed and actual results may differ materially from such statements. The information in this release is provided only as of the date of this release, and ROKIT undertakes no obligation to update any forward-looking statements contained in this release on account of new information, future events, or otherwise, except as required by law.

February 11, 2019 by admin 0 Comments

ROKIT Healthcare starts the world’s first…

“ROKIT Healthcare starts the world’s first 3D bio-printing self-cartilage regenerative clinical trial with Harvard Medical School, Massachusetts General Hospita”– ROKIT Healthcare

  • Opens up possibilities to regenerate cartilage with self-cell instead of metal artificial joint

  • Developing 3D cartilage regeneration method beyond the limit of current 2D injection therapy

ROKIT Healthcare(CEO Seo-Whan You) starts a large-scale animal experiment, that develops human long-term regeneration platform, produced an autologous cell cartilage structure with a 3D bio-printer and successfully proved the effect of autologous cartilage regeneration through animal experiments in South Korea, with MGH(Massachusetts General Hospital). The cartilage regeneration procedure using the 3D bio printer developed by Rokit Healthcare Co., Ltd. reproduces the shape of the damaged cartilage tissue from the MRI / CT data in a patient-customized manner. They have applied for domestic and foreign patents last year on using bio ink to regenerate damaged cartilage area with minimal incision.

Conventional injection cartilage therapy has many structural limitations in treating very complex 3-D human cartilage, but since it is an innovative method of regenerating autografts by outputting three-dimensional images of the damaged area correctly, It is a state-of-the-art new medical technology.

Dr. Charles Bragdon, deputy director of the MGH Harris Orthopedics Lab, said that the 3-dimensional cartilage regeneration technique developed at Rokit Healthcare will be a technique that can be used for the treatment of degenerative arthritis caused by aging. He will present the technology at The American Society of Orthopedic Surgeons (AAOS),and willing to collaborate with global cartographic orthopedic surgeons for clinical application studies.

“In the first half year, we will conduct research on human subjects as early as this year.” Yoo Seok-hwan, CEO of Rokit Healthcare, said. They have already confirmed that the cartilage tissue produced by our cartilage regenerating technique is differentiated into hyaline cartilage rather than fibrous cartilage through domestic animal experiments.

February 10, 2019 by admin 0 Comments

Rokit Healthcare has recently increase capital…

ROKIT Healthcare, a company that develops human long-term regeneration platforms, raised KRW 11 billion investments. The company plans to develop a long-term organ regenerative platform and to go public the listing on the KOSDAQ.

According to the venture capital industry, Rokit Healthcare has recently increase capital by issuing new stocks to institutional investors. The investment attraction was conducted for a total of three institutions including Korea Development Bank and Daily Partners including KB Investment, which was an existing investment company. The total investment is 11 billion KRW, which is estimated to have tripled the enterprise value compared to the investment attraction which took place about a year and six months ago. In addition to the investment completed this year, Rokit Healthcare is also undergoing additional institutional investment of approximately KRW 20 billion.

Rokit Healthcare plans to launch a full-scale global commercialization of its long-term renewal platform as a result of this investment inducement. The investment will be used for the development costs of the long-term reconstruction platform such as skin regeneration and cartilage regeneration platform using the 3D bio printer “INVIVO” developed by Rokit Healthcare and company operating funds. In addition, it said that it is concluding negotiations for additional investment of about 20 billion won in the first quarter of 2019.

Rokit Healthcare selected Mirae Asset Daewoo Securities as its managing director in July last year and is spurring the company’s public offering.

Rokit Healthcare is a bio-venture company founded in 2012 by CEO Seok-Hwan Yoo, who was CEO of Celltrion Healthcare. “In 2016, we succeeded in developing and launching INVIVO, the world’s first desktop 3D bio-printer, and is conducting research and development to provide personalized long-term renewable medical services using 3D bio-printers” he said. According to company officials, Rokit Healthcare will launch a skin rejuvenation medical platform service in South Korea and abroad after completing clinical trials for skin regeneration in the first half of this year.

February 10, 2019 by admin 0 Comments

Rokit health care makes inroads in the human…

“Rokit health care makes inroads in the human organ reproduction by establishing Tissue Bank”– ROKIT Healthcare

ROKIT Healthcare, a company that develops human long-term regeneration platform, has been granted permission to establish a tissue bank and is currently undergoing an import approval process from the FDA (Food and Drug Administration)

Rokit Healthcare Tissue Bank will donate and distribute cartilage (costal cartilage) that can be transplanted from a postmortem human tissue donor, and use it for long-term regeneration by transplanting and processing into patients who need transplantation or regeneration. .

Yoo Seok-hwan, CEO of Rokit Healthcare, said, “We will work with human organ bank in the US to resolve the shortage of organ donation in South Korea and receive the approval from the pharmacy to provide patients with organ regeneration and rehabilitation. And we hope that the safe supply of human tissue implants will be boosted.”

“This year will be our milestone as we will contribute to stable supply and demand by securing all the safe, self-derived cells and allogenic biomaterials derived from human body by donating tissues through tissue banks.”

February 10, 2019 by admin 0 Comments

World’s First 3D Human Stem Cell Skin…

“World’s First 3D Human Stem Cell Skin Regeneration Clinical Practice”– ROKIT Healthcare

  • Forming high cell adhesion rate, cell density and autologous extracellular matrix through bioprinting can solve the problems of current stem cell injection therapy of low cell adhesion and cancer induction.
  • Future applications will expand with scar removal, diabetic foot, and pressure ulcer.
  • Signed on MOU on technical cooperation for export of skin regeneration platform to Europe and Turkey

ROKIT Healthcare, a company that develops human long-term regeneration platform, is to be in clinical practice from February. For the first time in the world, Rokit Healthcare starts trials to immunize stem cells and extracellular matrix separated from autologous fat using 3D bio-printer (INVIVO). They are working with Yonsei Severance Hospital and Idea Hospital. “3D autologous stem cell skin regeneration method,” which prints and transplants a donor-free dermis without rejection.

About this new treatment, Rokit Healthcare Ltd (CEO, Seok Hwan You) said it is a new way of solving the most difficult limitations of stem cell therapy. The main problem with current syringe stem cell therapy approaches is that only 10% of the injected cells survive and the remaining 90% or more of the cells are washed away from the affected area and delivered to unintended sites, and it can be carcinogenic. Another problem is that when stem cells are delivered by injection, they are not uniformly distributed onto the affected area, so it is difficult to predict the therapeutic effect. Furthermore, when the cells are densely packed, nutrients and oxygen cannot be delivered, consequently, the cells that are supposed to be cure the diseased area die.

In Rokit Healthcare, it is possible to treat lesions of the same size with the amount of stem cells 10 times lower than the injection therapy due to the fact that the cells are not lost as the printed stem cells and extracellular matrix are outputted as a solid form of the hydrogel. Also, since the cells are output and maintained at an equal density, the proliferation and viability of cells can be greatly enhanced.

In addition, the autologous extracellular matrix (extracellular matrix) was used to rapidly grow cells to accelerate engraftment and tissue formation, and a bioactive scaffold was constructed as an autologous extracellular matrix. . In this way, the bioactive scaffold made of autologous extracellular matrix contains growth factors and cytokines, so that the cell is a network and plays a very important role in the induction of blood vessels and the formation of new blood vessels for growth, differentiation, and engraftment.

Another benefit of this treatment is that it is a non-stitching treatment, so it is effective in minimizing scarring and also for plastic scar reconstruction. This excellent global clinical section of Korea is proceeding with clinical trials in the US and Europe. Also the MOU on technology exporting, skin regeneration platforms, with Slovakia and large hospitals in Turkey has been confirmed in December. If this treatment is successful, it can be extended to burns, diabetic foot as well as scar reconstruction.  There is much attention towards Rokit Healthcare to open up new horizons for advanced medical care.

February 6, 2019 by admin 0 Comments

3D 프린터로 피부 재생, 5월 세계 첫 상용화

▲유석환 로킷헬스케어 대표가 서울 금천구 본사에서 바이오 3차원(3D) 프린터 ‘인비보’의 작동원리와 기능 등을 설명하고 있다.

올해 안에 세계 최초로 3차원(3D) 바이오프린팅 재생의료를 상용화할 계획입니다. 최종 목표는 인공장기를 생산하는 거죠. – ROKIT Healthcare Chairman/CEO You Seokhwan

  • 심장근육 대체 ‘하트패치’도 개발

  • 연내 전임상…2021년 상업화

  • 올해 말 코스닥 상장 추진

석환 로킷헬스케어 대표는 “지난해 손상된 피부를 재생하는 기술을 개발하고 현재 피부 상처, 당뇨병성 족부궤양, 욕창 등에 대한 임상을 세브란스병원, 이데아성형외과 등에서 하고 있다”며 이렇게 말했다. 피부 재생 시술은 오는 5월부터 상업화할 수 있을 것으로 보인다. 당뇨병성 족부궤양, 욕창 등도 연말께 의료기관에서 3D 프린터로 치료받을 수 있을 전망이다. 환자 맞춤형 치료에 큰 잠재력이 있다는 평가를 받는 3D 바이오프린터 재생의료가 마침내 현실화하는 것이다.

“3D 바이오프린팅 재생의료 플랫폼 제공”

2012년 설립된 로킷헬스케어는 2016년 자체 개발한 3D 바이오프린터 ‘인비보’를 출시했다. 인비보는 기존 제품과 가격대는 비슷하면서도 미국 식품의약국(FDA)이 허가한 모든 바이오잉크로 세포가 손상되지 않게 제품을 출력한다. 지금까지 미국, 독일 등 10여 개국에 300대 이상 팔았다. 유 대표는 2007년부터 셀트리온헬스케어 대표를 지내다가 창업했다. 그는 “소비자의 취향을 최대한 반영하는 다품종 소량생산으로 산업 환경이 변하고 있다는 생각에 3D 프린터에 주목하게 됐다”고 했다.

유 대표는 로킷헬스케어가 단순한 제조업체가 아니라 플랫폼 기업이라고 강조했다. 지난해 9월 회사 이름을 ‘로킷’에서 ‘로킷헬스케어’로 바꾼 것도 그런 취지에서다. 그는 “처음엔 3D 바이오프린터를 제조하는 것으로 시작했지만 지금은 3D 바이오프린팅 기술로 환자에게 맞춤형 재생의료를 제공하는 플랫폼 기업을 목표로 하고 있다”고 했다. 의료기관에 3D 바이오프린팅 재생의료에 필요한 각종 장비와 소모품, 기기, 서비스 등을 제공하는 게 이 회사의 비즈니스 모델이다. 그는 “우리가 하고 있는 것은 3D 바이오프린터로 할 수 있는 치료의 10%도 안 된다”며 “우리 플랫폼을 이용해 다양한 재생의료를 선보일 것”이라고 밝혔다.

이 회사는 3D 바이오프린터 제작은 물론 인체조직을 만드는 데 쓰이는 바이오잉크, 인공장기 토대가 되는 오르가노이드 등을 개발하고 있다. 오르가노이드는 혈관 없이 생존할 수 있는 최소 기관이다. 유 대표는 “직원의 80%가 바이오를 전공했고 박사급 인력만 7명에 달한다”며 “지속적으로 바이오 기술자를 영입해 올해 인력을 50% 이상 늘릴 것”이라고 했다.

연골, 망막, 심장근육까지 재생

로킷헬스케어는 피부 재생, 연골, 망막, 심장근육 등 여러 신체조직을 재생하는 데 3D 바이오프린팅 기술이 유효한지 검증하고 있다. 동물 20여 마리를 대상으로 한 전임상에서 연골 재생 효과를 확인했다. 이달부터 미국 하버드대 의대 부속 매사추세츠병원과 함께 연골재생치료 동물실험을 한다. 상반기까지 미국, 유럽 등지에서 실험을 마친 뒤 연말께 환자에게 적용할 예정이다. 재생의료 기술을 접목한 화장품도 하반기께 출시한다. 3D 프린터로 제작한 모발 이식도 연내 상용화할 계획이다.

심근경색으로 괴사한 심장근육 일부를 대체할 수 있는 ‘하트패치’는 독일의 유수 연구기관인 프라운호퍼 국립연구소와 공동 연구하고 있다. 사람의 심근세포를 활용해 혈관 없이 생존하면서 수축과 이완을 반복하는 동전 크기의 패치를 제작한 뒤 괴사한 심근 조직을 떼어낸 자리에 붙이면 심장근육으로 바뀐다. 올해 전임상을 시작해 2021년께 상업화할 계획이다. 실명 위험이 큰 황반변성을 치료할 수 있는 망막 시트도 개발 중이다.

로킷헬스케어는 세계 시장을 겨냥하고 있다. 대우자동차 유럽본부 최고운영책임자, 미국 보안업체 타이코 아시아태평양 총괄수석부사장, 셀트리온헬스케어 대표 등을 지내며 쌓은 글로벌 비즈니스 감각과 풍부한 네트워크가 큰 자산이다. 유 대표는 “연골 재생 시장은 124조원, 피부 재생 시장은 60조원에 달한다”며 “미국, 유럽 등 선진국을 포함해 재생의료 규제 장벽이 높지 않은 일본, 터키, 인도 등에 적극적으로 진출할 것”이라고 말했다. 로킷헬스케어는 올해 말 코스닥시장에 상장할 계획이다.

February 1, 2019 by admin 0 Comments

Effect of Temperature on the Emission Rate of Particulate Matter during 3D Printing and Characteristics of Initial Peak

Authors
Haejoon Jeon
Abstract
Three dimensional (3D) printers based on fused deposition modeling (FDM) technology are rapidly becoming popular. Various harmful substances including gas and particulate matter are known to be released during 3D printing by heating thermoplastic materials at high temperature conditions. Previous study reported that the particle concentration increased as the temperature rising and occurred highest emission at early stages of printing although limited paper mentioned about the effect of temperature on the particle emission and the high concentration of the early printing. The aims of this study were to evaluate the effect of temperature on the emission rate of particulate matter during three-dimensional (3D) printing using different filament types and to investigate the mechanism of the highest concentration peak in early stage of printing.

February 1, 2019 by admin 0 Comments

3D printed PLCL/hydrogel complex scaffolds using decellularized adipose tissue development

Authors
Soojin Lee
Abstract
Adipose tissue regeneration has been studied for many patients who had a burn defect, traumatic injury and mastectomy to improve their quality of life. The number of surgical operations is increasing due to the increase in the number of patients newly diagnosed with breast cancer. Although the studies on adipose tissue regeneration using natural polymer and synthetic polymer have been done, but disadvantages such as fast degradation rate and mismatch of mechanical properties still exist. So we set up three strategies to overcome the limits of previous researches. First, poly (lactide-co-caprolactone) (PLCL), very elastic and biocompatible polymer, was synthesized to provide proper mechanical properties and three dimensional structure for adipose tissue engineering. It also provide a stable tertiary structure to prevent the fast degradation while the adipose tissue regenerate. Secondly, to induce adipogenic differentiation and neo-vascularization for large sized tissue, decellularized extracellular matrix (dECM) was used to promote angiogenesis for efficient blood supply. Lastly, 3D printing technique was used to fabricate a patient-specific scaffold.<br /> The PLCL and adipose tissue derived dECM hydrogel was printed through dual nozzle system and the complex construct composed of PLCL and hydrogel was fabricated (15 mm x 15 mm x 4.0 mm). Flexibility and stretchability of the PLCL copolymer were maintained after 3D printing. Adipose tissue derived dECM based hydrogel was prepared as a biocompatible bioink. Since 1:3-adECM: collagen showed the best cell viability and printability than other ratio of hydrogels, it was used for further experiments. We evaluated angiogenesis and macrophage infiltration of the samples while in vivo experiments and investigated the potential for adipose tissue regeneration. A lot of matured blood vessels were observed more in the Hydrogel-PLCL complex constructs than in PLCL only scaffolds. Moreover, the higher expression of M2 macrophage for tissue repair and of adipogenic differentiation relative genes was measured in the Hydrogel-PLCL complex constructs by immunofluorescent analysis and real-time PCR, respectively. Based on these results, we anticipate that our constructs will be a promising alternative for adipose tissue regeneration.