October 1, 2020 by admin 0 Comments

3D printing of self-healing ferrogel prepared from glycol chitosan, oxidized hyaluronate, and iron oxide nanoparticles

Eun Seok Ko a,1, Choonggu Kim a,1, Youngtae Choi a, Kuen Yong Lee a,b
Hydrogel systems that show self-healing ability after mechanical damage are receiving increasing attention. However, self-healing hydrogels suitable for biomedical applications are limited owing to complex preparation methods. Furthermore, few studies have demonstrated the self-healing property of ferrogels. In this study, we demonstrated that glycol chitosan (GC) and oxidized hyaluronate (OHA) can be used to form a self-healing ferrogel in the presence of superparamagnetic iron oxide nanoparticles (SPIONs) without additional chemical cross-linkers. The overall characteristics of GC/OHA/SPION ferrogel varied based on the GC/OHA ratio, SPION content, and total polymer concentration. Interestingly, GC/OHA/SPION ferrogel was used to fabricate 3D-printed constructs of various shapes via an extrusion printing method. These constructs were responsive to the magnetic field, suggesting their potential application in 4D printing. This approach to developing self-healing ferrogels with biocompatible polysaccharides may prove useful in designing and fabricating drug delivery systems and tissue engineering scaffolds, via 3D printing.

September 16, 2020 by admin 0 Comments

Augmented peripheral nerve regeneration through elastic nerve guidance conduits prepared using a porous PLCL membrane with a 3D printed collagen hydrogel

Jin Yoo ‡a, Ji Hun Park ‡b, Young Woo Kwon ‡c, Justin J. Chung a, In Cheul Choi d, Jae Joon Nam d, Hyun Su Lee e, Eun Young Jeon a, Kangwon Lee e, Soo Hyun Kim af, Youngmee Jung *ag, and Jong Woong Park *d
Peripheral nerve injury results in significant sensory and motor functional deficits. Although direct neurorrhaphy in the early phase may reduce its devastating effects, direct end-to-end neurorrhaphy is sometimes impossible owing to a defect at the injured site of the nerve. Autogenous nerve graft is a primary consideration for peripheral nerve defects; however, significant morbidity of the donor site is inevitable. Recently, the treatment using engineered synthetic nerve conduits has been regarded as a promising strategy to promote the regeneration of peripheral nerve defects. In this study, we developed longitudinally oriented collagen hydrogel-grafted elastic nerve guidance conduits (NGC) to reconstruct sciatic nerve defects. An elastic NGC was prepared by using poly(lactide-co-caprolactone) (PLCL), and electrospun PLCL was adopted to fabricate nanoporous structures with appropriate permeability for nerve regeneration. Oriented collagen hydrogels were prepared by the 3D printing method to achieve a microscale hydrogel pattern. Based on sciatic nerve injury models in rats, we confirmed the beneficial effects of the NGC with 3D printed collagen hydrogel on axonal regeneration and remyelination along with superior functional recovery in comparison with the NGC filled with the bulk collagen hydrogel. It is believed that the aligned collagen hydrogels provide a preferable environment for nerve regeneration, functioning as an oriented guidance path. In conclusion, the PLCL nerve guide conduit containing a 3D printed aligned collagen hydrogel can be useful for peripheral nerve regeneration.

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 9, 2020 by admin 0 Comments

3D Printed Bioresponsive Devices with Selective Permeability Inspired by Eggshell Membrane for Effective Biochemical Conversion

Yale Jeon, Min Soo Jeon, Jongoh Shin, Sangrak Jin, Jonghun Yi, Seulgi Kang, Sun Chang Kim, Byung-Kwan Cho, Jung-Kul Lee, and Dong Rip Kim*
Eggshell membrane has selective permeability that enables gas or liquid molecules to pass through while effectively preventing migration of microbial species. Herein, inspired by the architecture of the eggshell membrane, we employ three-dimensional (3D) printing techniques to realize bioresponsive devices with excellent selective permeability for effective biochemical conversion. The fabricated devices show 3D conductive carbon nanofiber membranes in which precultured microbial cells are controllably deployed. The resulting outcome provides excellent selective permeability between chemical and biological species, which enables acquisition of target responses generated by biological species confined within the device upon input signals. In addition, electrically conductive carbon nanofiber networks provide a platform for real-time monitoring of metabolism of microbial cells in the device. The suggested platform represents an effort to broaden microbial applications by constructing biologically programmed devices for desired responses enabled by designated deployment of engineered cells in a securely confined manner within enclosed membranes using 3D printing methods.

May 15, 2020 by admin 0 Comments

Exfoliated graphene/thermoplastic elastomer nanocomposites with improved wear properties for 3D printing

Hyerin Jeon a,b,1, Youn Kim b,1, Woong-Ryeol Yu a, Jea UkLee b
Although three-dimensional (3D) thermoplastic elastomer printing has been studied, the unsatisfactory mechanical properties of 3D-printed elastomers, especially their substandard wear characteristics, make it difficult to use them in industrial products or processes. In this study, thermoplastic elastomer nanocomposites with improved wear properties were fabricated using thermoplastic polyether elastomer (TPEE), with surface-modified carbon black (CB), or electrochemically exfoliated graphene through multiple extrusion processes. The surface-modified CB/TPEE composite showed about four times more wear resistance and 26% improvement in tensile strength as compared to bare TPEE resin. The graphene/TPEE composite with only 1 wt% graphene exhibited an elevenfold increase in wear resistance and 43% improvement in the tensile strength owing to the high dispersibility and lubricating effect of the two-dimensional graphene filler. Graphene/TPEE composites were extruded into filaments for 3D printing. Three-dimensional printed products made from the nanocomposites have much higher wear resistance than 3D products of bare TPEE resin, demonstrating that graphene and TPEE nanocomposites are well suited for manufacturing a wide variety of complex electronic and mechanical components with excellent wear characteristics.

May 12, 2020 by admin 0 Comments

Bactericidal Lubricating Synthetic Materials for Three-Dimensional Additive Assembly with Controlled Mechanical Properties

Jihoon Ahn, Yale Jeon, Kang Won Lee, Jonghun Yi, Sun Woo Kim, and Dong Rip Kim*
3D printable synthetic materials have been developed to realize desired surface and mechanical properties. Lubricating synthetic surfaces have broad technological impacts on many applications including food packaging, microfluidic systems, and biomedical devices. However, combining soft materials with lubricants leads to significant phase separation and swelling phenomena, together with lowered mechanical strength, impeding full utilization of lubricating synthetic surfaces with desired shapes in a highly controllable manner. Here, we report a new platform to create a 3D printable lubricant–polymer composite (3D-LUBRIC) for the seamless fabrication of multidimensional structures with diverse functionalities. The rationally designed lubricant–polymer mixtures including silica aerogel particles not only exhibit suitable rheological properties for direct ink writing without phase separation but also enable the deterministic additive assembly of heterogeneous materials, which have large mismatches of oil permeability, with no distinct shape distortion. While exhibiting excellent lubricating properties for a variety of liquids, 3D-LUBRIC shows tunable mechanical properties with desired functionalities, such as optical transparency, flexibility and stretchability, and anti-icing and antibacterial/bactericidal properties. We employ the proposed platform to fabricate self-cleanable containers and antibacterial/bactericidal medical tubes. Our platform can offer new opportunities for building low-adhesive, multifunctional synthetic materials with customized shapes for diverse applications.

April 5, 2020 by admin 0 Comments

Hot-Melt 3D Extrusion for the Fabrication of Customizable Modified-Release Solid Dosage Forms

Jaemin Lee, Chanwoo Song, Inhwan Noh, Sangbyeong Song and Yun-Seok Rhee *
In this work, modified-release solid dosage forms were fabricated by adjusting geometrical properties of solid dosage forms through hot-melt 3D extrusion (3D HME). Using a 3D printer with air pressure driving HME system, solid dosage forms containing ibuprofen (IBF), polyvinyl pyrrolidone (PVP), and polyethylene glycol (PEG) were printed by simultaneous HME and 3D deposition. Printed solid dosage forms were evaluated for their physicochemical properties, dissolution rates, and floatable behavior. Results revealed that IBF content in the solid dosage form could be individualized by adjusting the volume of solid dosage form. IBF was dispersed as amorphous state with enhanced solubility and dissolution rate in a polymer solid dosage form matrix. Due to absence of a disintegrant, sustained release of IBF from printed solid dosage forms was observed in phosphate buffer at pH 6.8. The dissolution rate of IBF was dependent on geometric properties of the solid dosage form. The dissolution rate of IBF could be modified by merging two different geometries into one solid dosage form. In this study, the 3D HME process showed high reproducibility and accuracy for preparing dosage forms. API dosage and release profile were found to be customizable by modifying or combining 3D modeling.

January 5, 2020 by admin 0 Comments

Biobased thermoplastic elastomer with seamless 3D-Printability and superior mechanical properties empowered by in-situ polymerization in the presence of nanocellulose

Jun Mo Koo (a, b, 1), Jaeryeon Kang (a, 1), Sung-Ho Shin (a), Jonggeon Jegal (a), Hyun Gil Cha (a), Seunghwan Choy (c), Minna Hakkarainen (b), Jeyoung Park (a, d), Dongyeop X. Oh (a, d), Sung Yeon Hwang (a, d)
A biobased and biocompatible thermoplastic elastomer (TPE) with superior 3D printability was demonstrated with great potential for customized manufacturing technologies and fabrication of biointegrated devices. The inherent structural and stereochemical disadvantages of biobased monomers, such as 2,5-furandicarboxylic acid, in comparison with today used petroleum based monomers like terephthalic acid generally lead to lower mechanical performance for the biobased replacement polymers. This is additionally enhanced by poor interfacial adhesion and fusion commonly encountered during customized manufacturing technologies like 3D printing. Herein, we demonstrate that in-situ polymerization in the presence of trace amounts of cellulose nanocrystals (CNCs) can homogeneously distribute the nanofiller leading to dramatically strengthened thermally 3D-printable bio-furan-based TPE. This TPE exhibited a tensile strength of 67 MPa which is 1.5–7-fold higher than the values reported for silicone and thermoplastic urethane, which are widely used in biomedical applications. In addition, the TPE had an impressive extensibility of 860% and negligible in vivo cytotoxicity; such properties have not been reported to date for bio-based or petrochemical TPEs. While a petrochemical 3D printed TPE counterpart retained only half of the tensile strength compared to the hot-pressed analogue, the 3D-printed biobased TPE in-situ modified with nanocellulose maintained 70–80% of its strength under the same experimental conditions. This is explained by inter-diffusion between interfaces facilitated by the nanocellulose and the furan rings. Using the ergonomic shape of a wrist as a 3D-printable design, we successfully manufactured a wearable thermal therapeutic device from the nanocellulose modified biobased TPE, giving promise for wide variety of future applications.

October 16, 2019 by admin 0 Comments

Evaluation of Sericin Containing Gel as a Photoinitiator-Free Printable Biomaterial

Mijin Jang, Bo Kyung Park, Jeung Soo Huh, Jeong Ok Lim
Current major challenge in three-dimensional (3D) printing of biological tissues is lack of proper printable biomaterials. Development of 3D printable biomaterials for safely and efficiently printing biological substitute is challenging. Most of the hydrogel-based biomaterials include photoinitiator to be crosslinked by either ultraviolet or visible light to obtain mechanically stable gel. However, use of crosslinking chemical has concerns for its potential harm to biological substances. Our study aimed to formulate and optimize a new printable biomaterial without any crosslinking chemical, still having appropriate rheological, chemical, and biological properties. We investigated the potential of a silk protein, sericin, which is known to be mechanically stable and has anti-inflammatory and angiogenic properties. The results demonstrated that a sericin-based hydrogel can be an excellent material as it is easy to print, gelling, not toxic, stable, and cost effective.

May 14, 2019 by admin 0 Comments

Development of a semi-customized tongue displacement device using a 3D printer for head and neck IMRT

Chae-Seon Hong, Dongryul Oh, Sang Gyu Ju, Yong Chan Ahn, Cho Hee Na, Dong Yeol Kwon & Cheol Chong Kim
Purpose To reduce radiation doses to the tongue, a patient-specific semi-customized tongue displacement device (SCTDD) was developed using a 3D printer (3DP) for head and neck (H&N) radiation therapy (RT). Dosimetric characteristics of the SCTDD were compared with those of a standard mouthpiece (SMP). Materials and methods The SCTDD consists of three parts: a mouthpiece, connector with an immobilization mask, and tongue displacer, which can displace the tongue to the contralateral side of the planning target volume. Semi-customization was enabled by changing the thickness and length of the SCTDD. The instrument was printed using a 3DP with a biocompatible material. With the SCTDD and SMP, two sets of planning computed tomography (CT) and tomotherapy plans were obtained for seven H&N cancer patients. Dosimetric and geometric characteristics were compared. Results Using the SCTDD, the tongue was effectively displaced from the planning target volume without significant tongue volume change compared to the SMP. The median tongue dose was significantly reduced (29.6 Gy vs. 34.3 Gy). The volumes of the tongue receiving a dose of 15 Gy, 30 Gy, 35 Gy, 45 Gy, and 60 Gy were significantly lower than using the SMP. Conclusion The SCTDD significantly decreased the radiation dose to the tongue compared to the SMP, which may potentially reduce RT-related tongue toxicity.