March 3, 2023 by admin 0 Comments

Posted in SCI-class international journals for verifying the efficacy of renal failure treatment patches, renal fibrosis in renal failure models, and reduced tubal abnormalities.

The efficacy of the developed renal failure treatment patch has been verified through preclinical studies. The results of the study were adopted as a cover paper in December last year in the leading journal Tissue Engineering Part C as a paper titled “Improvement of renal fibrosis of self-entum patches printed on 3D bio-printers.

This study was conducted in collaboration with a research team from the Department of Renal Internal Medicine and Pathology at Seoul National University and the Department of Renal and Pancreatic Transplantation at Asan Hospital. A 3D printing-based treatment patch was implanted into an animal model of kidney failure to confirm the effect of reducing renal fibrosis and tubal abnormalities, which are major symptoms of kidney failure. In addition, the research team found that treatment patches in damaged kidneys regulate gene expression and help regenerative treatment through single-cell sequencing.

Link to the paper : 논문_2022_KIDNEY_Three-dimensional bio-printed autologous omentum patch ameliorates unilateral ureteral obstruction induced renal fibrosis (1)

January 17, 2023 by admin 0 Comments

Skin Regeneration_DFU Clinical Test Article in Malaysia

New Paradigm in Diabetic Foot Ulcer Grafting Techniques Using 3D-Bioprinted Autologous Minimally Manipulated Homologous Adipose
Tissue (3D-AMHAT) with Fibrin Gel Acting as a Biodegradable Scaffold

Author : Mohd Yazid Bajuri, Jeehee Kim, Yeongseo Yu and Muhammad Shazwan Shahul Hameed

Special Issue
Hydrogel-Based Scaffolds with a Focus on Medical Use
Edited by Dr. Federica Re and Dr. Elisa Borsani

Abstract: Adipose tissue is an abundant source of extracellular substances that support the tissue repair process. This pilot study was carried out to determine the efficacy of 3D-bioprinted autologous adipose tissue grafts on diabetic foot ulcers (DFUs), with fibrin gel used to stabilise the graft. This
was a single-arm pilot study in a tertiary hospital that provides diabetic wound care services. A total of 10 patients with a DFU were enrolled, and the primary endpoint was complete healing within 12 weeks. The secondary endpoints were wound size reduction, time to healing, and adverse events. Seven out of ten patients showed complete healing of their DFU within 12 weeks (at 2, 4, 5, 10, and 12 weeks, respectively). The wound size reduction rate was significantly and progressively reduced over time. According to our data, autologous adipose tissue grafting using a 3D bioprinter, with
the addition of fibrin gel that acts as a scaffold, promotes wound healing with high-quality skin reconstruction. Throughout this study period, no adverse events were observed.

Keywords: 3D bioprinter; autologous adipose tissue graft; diabetic foot ulcer; fibrin glue;
biodegradable scaffold; tissue regeneration

Downloads : Skin_DFU Paper_Malaysia_Gels_230110

March 1, 2022 by admin 0 Comments

Evaluation of Three-Dimensional Bioprinted Human Cartilage Powder Combined with Micronized Subcutaneous Adipose Tissues for the Repair of Osteochondral Defects in Beagle Dogs

Authors
Jina Ryu(1), Mats Brittberg(2, 3), Bomi Nam(1), Jinyeong Chae(1), Minju Kim(1), Yhan Colon Iban(4), Martin Magneli(4, 5, 6), Eiji Takahashi(4, 5, 7), Bharti Khurana(8), Charles R Bragdon(4, 5)
Abstract
Cartilage lesions are difficult to repair due to low vascular distribution and may progress into osteoarthritis. Despite numerous attempts in the past, there is no proven method to regenerate hyaline cartilage. The purpose of this study was to investigate the ability to use a 3D printed biomatrix to repair a critical size femoral chondral defect using a canine weight-bearing model. The biomatrix was comprised of human costal-derived cartilage powder, micronized adipose tissue, and fibrin glue. Bilateral femoral condyle defects were treated on 12 mature beagles staged 12 weeks apart. Four groups, one control and three experimental, were used. Animals were euthanized at 32 weeks to collect samples. Significant differences between control and experimental groups were found in both regeneration pattern and tissue composition. In results, we observed that the experimental group with the treatment with cartilage powder and adipose tissue alleviated the inflammatory response. Moreover, it was found that the MOCART score was higher, and cartilage repair was more organized than in the other groups, suggesting that a combination of cartilage powder and adipose tissue has the potential to repair cartilage with a similarity to normal cartilage. Microscopically, there was a well-defined cartilage-like structure in which the mid junction below the surface layer was surrounded by a matrix composed of collagen type I, II, and proteoglycans. MRI examination revealed significant reduction of the inflammation level and progression of a cartilage-like growth in the experimental group. This canine study suggests a promising new surgical treatment for cartilage lesions.

October 12, 2021 by admin 0 Comments

Management of Diabetic Foot Ulcer with MA–ECM (Minimally Manipulated Autologous Extracellular Matrix) Using 3D Bioprinting Technology – An Innovative Approach

Authors
Rajesh Kesavan, Changam Sheela Sasikumar, V.B. Narayanamurthy, Arvind Rajagopalan, Jeehee Kim
Abstract
Chronic foot ulcers are the leading cause of prolonged hospitalization and loss of social participation in people with diabetes. Conventional management of diabetic foot ulcers (DFU) is associated with slow healing, high cost, and recurrent visits to the hospital. Currently, the application of autologous lipotransfer is more popular, as the regenerative and reparative effects of fat are well established. Herein we report the efficacy of minimally manipulated extracellular matrix (MA-ECM) prepared from autologous homologous adipose tissue by using 3D bioprinting in DFU (test group) in comparison to the standard wound care (control group). A total of 40 subjects were screened and randomly divided into test and control groups. In the test group, the customized MA-ECM was printed as a scaffold from the patient autologous fat using a 3D bioprinter device and applied to the wound directly. The control group received standard wound care and weekly follow-up was done for all the patients. We evaluated the efficacy of this novel technology by assessing the reduction in wound size and attainment of epithelialization. The patients in the test group (n = 17) showed complete wound closure with re-epithelialization approximately within a period of 4 weeks. On the other hand, most of the patients in the control group (n = 16) who received standard wound dressings care showed a delay in wound healing in comparison to the test group. This technique can be employed as a personalized therapeutic method to accelerate diabetic wound healing and may provide a promising potential alternative approach to protect against lower foot amputation a most common complication in diabetes.

December 16, 2020 by admin 0 Comments

Creation of bladder assembloids mimicking tissue regeneration and cancer

Authors
Eunjee Kim, Seoyoung Choi, Byunghee Kang, JungHo Kong, Yubin Kim, Woong Hee Yoon, Hwa-Rim Lee, SungEun Kim, Hyo-Min Kim, HyeSun Lee, Chorong Yang, You Jeong Lee, Minyong Kang, Tae-Young Roh, Sungjune Jung, Sanguk Kim, Ja Hyeon Ku & Kunyoo Shin
Abstract
Current organoid models are limited by their inability to mimic mature organ architecture and associated tissue microenvironments. Here we create multilayer bladder ‘assembloids’ by reconstituting tissue stem cells with stromal components to represent an organized architecture with an epithelium surrounding stroma and an outer muscle layer. These assembloids exhibit characteristics of mature adult bladders in cell composition and gene expression at the single-cell transcriptome level, and recapitulate in vivo tissue dynamics of regenerative responses to injury. We also develop malignant counterpart tumour assembloids to recapitulate the in vivo pathophysiological features of urothelial carcinoma. Using the genetically manipulated tumour-assembloid platform, we identify tumoural FOXA1, induced by stromal bone morphogenetic protein (BMP), as a master pioneer factor that drives enhancer reprogramming for the determination of tumour phenotype, suggesting the importance of the FOXA1–BMP–hedgehog signalling feedback axis between tumour and stroma in the control of tumour plasticity.

November 30, 2020 by admin 0 Comments

Biofabrication of 3D printed hydroxyapatite composite scaffolds for bone regeneration

Authors
Yoontae Kim(1), Eun-Jin Lee(1), Albert V. Davydov(2), Stanislav Frukhbeyen(1), Jonathan E. Seppala(3), Shozo Takagi(1), Laurence Chow(1) and Stella Alimperti(1)
Abstract
Biofabrication has been adapted in engineering patient-specific biosynthetic grafts for bone regeneration. Herein, we developed a 3D high-resolution, room-temperature printing approach to fabricate osteoconductive scaffolds using calcium phosphate cement (CPC). The non-aqueous CPC bioinks were composed of tetracalcium phosphate (TTCP), dicalcium phosphate anhydrous (DCPA), and Polyvinyl butyral (PVB) dissolved in either ethanol (EtOH) or Tetrahydrofuran (THF). They were printed in an aqueous sodium phosphate bath, which performs as a hardening accelerator for hydroxyapatite (HA) formation and as a retainer for 3D microstructure. The PVB solvents, EtOH or THF, affected differently the slurry rheological properties, scaffold microstructure, mechanical properties, and osteoconductivity...

October 21, 2020 by admin 0 Comments

Design and manufacturing of bioprinted gellan gum-based constructs representative of the articular cartilage

Authors
Gianluca Ciardelli, Piergiorgio Gentile, Chiara Tonda Turo
Abstract
Articular cartilage (AC) is a highly specialized tissue which exhibit topographical heterogeneity in terms of matrix composition and mechanical properties. Due to its avascular nature AC shows limited regenerative ability, therefore representing an excellent subject for tissue engineering (TE). Particularly, bioprinting is an emerging additive manufacturing technology that has already demonstrated its potential use in regenerative medicine and cartilage TE. It allows to recapitulate the tissues microstructure by a controlled deposition of “bioinks”, suspensions of cells alone or encapsulated in biomaterials. As cells source, mesenchymal stem cells and chondrocytes, both naturally found in AC, are mainly selected. Hydrogels are largely used as biomaterials for their ability to resemble soft tissues extracellular matrix (ECM), providing an ideal micro-environment for the embedded cells survival, proliferation and differentiation. Hydrogels are produced from synthetic and natural polymers, including gellan gum (GG), a biocompatible polysaccharide that has gained interest in cartilage TE because of its structural similarity to cartilage glycosaminoglycans (GAGs) and chondrogenic potential. The aim of this work was the design and manufacturing of 3D constructs mimicking AC by extrusion bioprinting. Particularly, this thesis objectives (OBJ) were: the synthesis and characterization (physico-chemical, morphological, mechanical) of methacrylated GG-based hydrogels subjected to a dual physical and photo-chemical crosslinking (OBJ1); the subsequent biofabrication via Rokit INVIVO bioprinter of in vitro constructs (OBJ2) and biological characterization of cell-laden constructs in terms of cells viability and AC tissue formation (OBJ3). The final stage of this work dealt with the manufacturing of osteoarthritis (OA) in vitro models, via culturing healthy models in cytokine-enriched culture medium, for future analysis on novel OA therapeutic treatments. Firstly, the success of GG methacrylate (GGMA) synthesis was demonstrated through FTIR and XPS analysis. Then, 4 photo-curable hydrogels were prepared: pure GGMA 2% w/v (GG2) and 3% w/v (GG3), and GGMA (respectively 2% w/v and 0.75% w/v) combined with 5% w/v manuka honey (GG/MH) and 10% w/v gelatin (GG/GEL). Gelation analysis at room temperature showed that GG3 and GG/GEL underwent sol-gel transition in ~1 minute, while GG2 and GG/MH in ~3 minute. Water uptake (WU) analysis demonstrated the strong hydrophilic nature of these hydrogels, reaching WU values up to ~1700%. Morphological analysis evidenced that they had an interconnected porous morphology with a mean pore diameter in the range 100-200 μm, suitable for AC applications. Similarly, mechanical analysis showed that hydrogels had a compressive Young’s modulus between ~25 and ~16 kPa, comparable to other natural hydrogels found in literature. GG2 and GG/MH hydrogels were selected as bioinks encapsulating human TERT immortalised stem cells differentiated into chondrocytes (Y201-C; 7x106 cells/ml). The double-crosslinked bioinks were successfully printed into stable constructs. Live/Dead assay demonstrated high cell viability for both bioprinted constructs. The GAGs quantification assay showed that Y201-C GAGs production increased over time in both hydrogels. Finally, scanning electron microscopy analysis showed that cells exhibited a typical chondrocytes rounded-shaped morphology and tended to aggregate in both healthy and OA GG2 constructs .

October 6, 2020 by admin 0 Comments

Fabrication of strontium-substituted hydroxyapatite scaffolds using 3D printing for enhanced bone regeneration

Authors
Hyun-Woo Kim & Young-Jin Kim
Abstract
The use of porous three-dimensional (3D) bioceramic scaffolds to facilitate the regeneration of bone defects has attracted great attention because their structures closely mimic the natural extracellular matrix. 3D printing is a versatile method for the fabrication of 3D scaffolds. In this study, 3D strontium-substituted hydroxyapatite (Sr-HA) bioceramic scaffolds were prepared by simple precipitation and 3D printing method. The resulting scaffolds exhibited interconnected microporous structures of strands and a single-phase crystal due to HA, meaning that no changes in the phase composition and microstructure of the scaffolds with the Sr content were observed. However, their dissolution rate and biological performance were substantially influenced by changes in the Sr content of the scaffolds. The optimal Sr content in the Sr-HA scaffolds for enhanced proliferation and differentiation of cells were identified by comparing four compositions of the Sr-HA scaffolds. The results of in vitro bioactivity tests demonstrated that the Sr5-HA scaffold with 0.05 of Sr/(Ca + Sr) molar ratio promoted more rapid cell proliferation, osteogenic differentiation, and cellular mineralization compared with the other scaffolds. Therefore, Sr-HA scaffolds have the potential for application in bone regeneration as new bone graft substitutes.

October 1, 2020 by admin 0 Comments

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

Authors
Eun Seok Ko a,1, Choonggu Kim a,1, Youngtae Choi a, Kuen Yong Lee a,b
Abstract
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

Authors
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
Abstract
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.