A Photo‐Crosslinkable Kidney ECM‐Derived Bioink Accelerates Renal Tissue Formation

3D bioprinting strategies in tissue engineering aim to fabricate clinically applicable tissue constructs that can replace the damaged or diseased tissues and organs. One of the main prerequisites in 3D bioprinting is finding an appropriate bioink that provides a tissue-specific microenvironment supporting the cellular growth and maturation. In this respect, decellularized extracellular matrix (dECM)-derived hydrogels have been considered as bioinks for the cell-based bioprinting due to their capability to inherit the intrinsic cues from native ECM. Herein, a photo-crosslinkable kidney ECM-derived bioink (KdECMMA) is developed that could provide a kidney-specific microenvironment for renal tissue bioprinting. Porcine whole kidneys are decellularized through a perfusion method, dissolved in an acid solution, and chemically modified by methacrylation. A KdECMMA-based bioink is formulated and evaluated for rheological properties and printability for the printing process. The results show that the bioprinted human kidney cells in the KdECMMA bioink are highly viable and mature with time. Moreover, the bioprinted renal constructs exhibit the structural and functional characteristics of the native renal tissue. The potential of the tissue-specific ECM-derived bioink is demonstrated for cell-based bioprinting that could enhance the cellular maturation and eventually tissue formation.

[1]  L. Dürselen,et al.  Decellularized cartilage matrix as a novel biomatrix for cartilage tissue-engineering applications. , 2012, Tissue engineering. Part A.

[2]  Lorenzo Moroni,et al.  Biofabrication strategies for 3D in vitro models and regenerative medicine , 2018, Nature Reviews Materials.

[3]  James J. Yoo,et al.  3D Bioprinted Human Skeletal Muscle Constructs for Muscle Function Restoration , 2018, Scientific Reports.

[4]  A. Atala,et al.  Decellularization for whole organ bioengineering , 2013, Biomedical materials.

[5]  A. Atala,et al.  Repopulation of porcine kidney scaffold using porcine primary renal cells. , 2016, Acta biomaterialia.

[6]  Anthony Atala,et al.  3D bioprinted functional and contractile cardiac tissue constructs. , 2018, Acta biomaterialia.

[7]  Sang Jin Lee,et al.  Synthetic Extracellular Microenvironment for Modulating Stem Cell Behaviors , 2015, Biomarker insights.

[8]  Anthony Atala,et al.  Optimization of gelatin–alginate composite bioink printability using rheological parameters: a systematic approach , 2018, Biofabrication.

[9]  Dong-Woo Cho,et al.  Precise stacking of decellularized extracellular matrix based 3D cell-laden constructs by a 3D cell printing system equipped with heating modules , 2017, Scientific Reports.

[10]  Z. Werb,et al.  Extracellular matrix degradation and remodeling in development and disease. , 2011, Cold Spring Harbor perspectives in biology.

[11]  May Win Naing,et al.  Organ-Derived Decellularized Extracellular Matrix: A Game Changer for Bioink Manufacturing? , 2018, Trends in biotechnology.

[12]  W. Jelkmann.  Physiology and Pharmacology of Erythropoietin , 2013, Transfusion Medicine and Hemotherapy.

[13]  Karthik Nagapudi,et al.  Photo-cross-linking of type I collagen gels in the presence of smooth muscle cells: mechanical properties, cell viability, and function. , 2003, Biomacromolecules.

[14]  Kwideok Park,et al.  Induction of re-differentiation of passaged rat chondrocytes using a naturally obtained extracellular matrix microenvironment. , 2013, Tissue engineering. Part A.

[15]  S. Badylak,et al.  Extracellular matrix hydrogels from decellularized tissues: Structure and function. , 2017, Acta biomaterialia.

[16]  P. Ronco,et al.  Role of extracellular matrix in kidney development and repair , 2003, Pediatric Nephrology.

[17]  F. Guilak,et al.  Genipin-crosslinked cartilage-derived matrix as a scaffold for human adipose-derived stem cell chondrogenesis. , 2013, Tissue engineering. Part A.

[18]  Kenneth M. Yamada,et al.  An extracellular matrix-specific GEF-GAP interaction regulates Rho GTPase crosstalk for 3D collagen migration , 2014, Nature Cell Biology.

[19]  W. Jelkmann.  Pathophysiology and Pharmacology of Erythropoietin , 1992 .

[20]  A. Habeeb,et al.  Determination of free amino groups in proteins by trinitrobenzenesulfonic acid. , 1966, Analytical biochemistry.

[21]  Valerie M. Weaver,et al.  The extracellular matrix at a glance , 2010, Journal of Cell Science.

[22]  Deok‐Ho Kim,et al.  Printing three-dimensional tissue analogues with decellularized extracellular matrix bioink , 2014, Nature Communications.

[23]  M. Detamore,et al.  The Bioactivity of Cartilage Extracellular Matrix in Articular Cartilage Regeneration , 2015, Advanced healthcare materials.

[24]  G. Dickson,et al.  Fabrication and repair of cartilage defects with a novel acellular cartilage matrix scaffold. , 2010, Tissue engineering. Part C, Methods.

[25]  Anthony Atala,et al.  Decellularization methods of porcine kidneys for whole organ engineering using a high-throughput system. , 2012, Biomaterials.

[26]  Guoping Chen,et al.  Decellularized matrices for tissue engineering , 2010, Expert opinion on biological therapy.

[27]  Richard O. Hynes,et al.  The Extracellular Matrix: Not Just Pretty Fibrils , 2009, Science.

[28]  Stephen F Badylak,et al.  An overview of tissue and whole organ decellularization processes. , 2011, Biomaterials.

[29]  Brian Derby,et al.  Printing and Prototyping of Tissues and Scaffolds , 2012, Science.

[30]  Wei Sun,et al.  Effect of bioink properties on printability and cell viability for 3D bioplotting of embryonic stem cells , 2016, Biofabrication.

[31]  Ji Hyun Kim,et al.  Three-dimensional cell-based bioprinting for soft tissue regeneration , 2016, Tissue Engineering and Regenerative Medicine.

[32]  Stephen F Badylak,et al.  Regenerative medicine and developmental biology: the role of the extracellular matrix. , 2005, Anatomical record. Part B, New anatomist.

[33]  R. Marchant,et al.  Design properties of hydrogel tissue-engineering scaffolds , 2011, Expert review of medical devices.

[34]  Xinqiao Jia,et al.  Hybrid multicomponent hydrogels for tissue engineering. , 2009, Macromolecular bioscience.

[35]  James J. Yoo,et al.  A 3D bioprinting system to produce human-scale tissue constructs with structural integrity , 2016, Nature Biotechnology.

[36]  Anthony Atala,et al.  3D bioprinting of tissues and organs , 2014, Nature Biotechnology.

[37]  Jos Malda,et al.  Extracellular matrix scaffolds for cartilage and bone regeneration. , 2013, Trends in biotechnology.

[38]  A. Atala,et al.  Potential Use of Autologous Renal Cells from Diseased Kidneys for the Treatment of Renal Failure , 2016, PloS one.

[39]  Chaenyung Cha,et al.  25th Anniversary Article: Rational Design and Applications of Hydrogels in Regenerative Medicine , 2014, Advanced materials.

[40]  K. Christman,et al.  Extracellular matrix hydrogel therapies: In vivo applications and development. , 2017, Acta biomaterialia.

[41]  J. K. Leach,et al.  Cell-derived matrix coatings for polymeric scaffolds. , 2012, Tissue engineering. Part A.