3D printed hydrogel scaffold promotes the formation of hormone-active engineered parathyroid tissue

The parathyroid glands are localized at the back of the thyroid glands in the cervical region and are responsible for regulation of the calcium level in the blood, through specialized cells that sense Ca2+ and secrete parathyroid hormone (PTH) in response to a decline in its serum level. PTH stimulates the skeleton, kidneys and intestines and controls the level of Ca2+ through specialized activities. Iatrogenic removal of the parathyroid gland, as well as damage to its vascular integrity during cauterization are some of the common complications of thyroid surgery. Therefore, regeneration and/or replacement of malfunctioning parathyroid tissue is required. Tissue engineering is an emerging and promising field for patients with organ failure with recent pioneering clinical applications. The success of tissue engineering strategy depends on the use of proper cells, bioactive factors that stimulate the activities of these cells and scaffolds that are produced to recapitulate the tissue structure and support the function of the engineered tissues. 3D printing is a developing strategy for the production of these scaffolds by providing a delicate control over their structure and properties. In this study, human primary parathyroid cells were successfully isolated and their viability and ability to secrete PTH upon stimulation with different levels of Ca2+ were shown in vitro. These cells were then seeded onto 3D printed alginate scaffolds and 3D bioprinted within alginate bioink, and cell viability as well as the ability to secrete PTH upon stimulation were also demonstrated. Therefore, functional hormone-active parathyroid tissue substitute was engineered in vitro through 3D printed hydrogels and autologous cells.

[1]  D. Cho,et al.  Tissue printing for engineering transplantable human parathyroid patch to improve parathyroid engraftment, integration, and hormone secretion in vivo , 2021, Biofabrication.

[2]  V. Hasırcı,et al.  3D cellular alignment and biomimetic mechanical stimulation enhance human adipose-derived stem cell myogenesis , 2020, Biomedical materials.

[3]  K. Yılmaz,et al.  3D bioprinting for the endocrine glands , 2020, Emergent Materials.

[4]  I. Sporea,et al.  Shear Wave Elastography versus Strain Elastography in Diagnosing Parathyroid Adenomas , 2020, International journal of endocrinology.

[5]  Dong-Woo Cho,et al.  3D cell printing of islet-laden pancreatic tissue-derived extracellular matrix bioink constructs for enhancing pancreatic functions. , 2019, Journal of materials chemistry. B.

[6]  Wen Feng Lu,et al.  3D bioprinting of tissues and organs for regenerative medicine☆ , 2018, Advanced drug delivery reviews.

[7]  Huey Wen Ooi,et al.  Thiol–Ene Alginate Hydrogels as Versatile Bioinks for Bioprinting , 2018, Biomacromolecules.

[8]  Vladimir Mironov,et al.  Bioprinting of a functional vascularized mouse thyroid gland construct , 2017, Biofabrication.

[9]  Murat Guvendiren,et al.  Recent Advances in Bioink Design for 3D Bioprinting of Tissues and Organs , 2017, Front. Bioeng. Biotechnol..

[10]  Keekyoung Kim,et al.  3D bioprinting for engineering complex tissues. , 2016, Biotechnology advances.

[11]  Ying Mei,et al.  3D Bioprinting for Vascularized Tissue Fabrication , 2016, Annals of Biomedical Engineering.

[12]  Pu Chen,et al.  Towards artificial tissue models: past, present, and future of 3D bioprinting , 2016, Biofabrication.

[13]  Anthony Atala,et al.  Printing Technologies for Medical Applications. , 2016, Trends in molecular medicine.

[14]  Nam-Trung Nguyen,et al.  Three-dimensional printing of biological matters , 2016 .

[15]  I. Jo,et al.  Differentiated tonsil-derived mesenchymal stem cells embedded in Matrigel restore parathyroid cell functions in rats with parathyroidectomy. , 2015, Biomaterials.

[16]  Anthony Atala,et al.  Essentials of 3D Biofabrication and Translation , 2015 .

[17]  Federica Chiellini,et al.  Additive manufacturing techniques for the production of tissue engineering constructs , 2015, Journal of tissue engineering and regenerative medicine.

[18]  S. Bornstein,et al.  Transplantation of bovine adrenocortical cells encapsulated in alginate , 2015, Proceedings of the National Academy of Sciences.

[19]  A. Boccaccini,et al.  Evaluation of Fibroblasts Adhesion and Proliferation on Alginate-Gelatin Crosslinked Hydrogel , 2014, PloS one.

[20]  James J. Yoo,et al.  Bioprinting technology and its applications. , 2014, European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery.

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

[22]  Ali Khademhosseini,et al.  3D biofabrication strategies for tissue engineering and regenerative medicine. , 2014, Annual review of biomedical engineering.

[23]  E. Schwarz,et al.  Endogenous tissue engineering: PTH therapy for skeletal repair , 2012, Cell and Tissue Research.

[24]  I. Martin,et al.  Ex situ bioengineering of bioartificial endocrine glands: a new frontier in regenerative medicine of soft tissue organs. , 2011, Annals of anatomy = Anatomischer Anzeiger : official organ of the Anatomische Gesellschaft.

[25]  K. M. Woods Ignatoski,et al.  Directed trans-differentiation of thymus cells into parathyroid-like cells without genetic manipulation. , 2011, Tissue engineering. Part C, Methods.

[26]  S. Badylak,et al.  Adrenal extracellular matrix scaffolds support adrenocortical cell proliferation and function in vitro. , 2010, Tissue engineering. Part A.

[27]  Vladimir Mironov,et al.  Towards organ printing: engineering an intra-organ branched vascular tree , 2010, Expert opinion on biological therapy.

[28]  Ranjna C Dutta,et al.  Cell-interactive 3D-scaffold; advances and applications. , 2009, Biotechnology advances.

[29]  Min Xu,et al.  Tissue-engineered follicles produce live, fertile offspring. , 2006, Tissue engineering.

[30]  C. Pesce,et al.  Intraoperative parathyroid hormone levels in thyroid surgery are predictive of postoperative hypoparathyroidism and need for vitamin D supplementation. , 2005, American journal of surgery.

[31]  Alex J. Brown,et al.  Parathyroid Cells Cultured in Collagen Matrix Retain Calcium Responsiveness: Importance of Three‐Dimensional Tissue Architecture , 2004, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[32]  G. Åkerström,et al.  Differentiation of human parathyroid cells in culture. , 2001, The Journal of endocrinology.

[33]  Haitao Cui,et al.  3D Bioprinting for Organ Regeneration , 2017, Advanced healthcare materials.

[34]  L. Mrózová,et al.  Hypocalcemia - the most common complication after total thyroidectomy. , 2014, Bratislavske lekarske listy.

[35]  P. Dubruel,et al.  The 3D printing of gelatin methacrylamide cell-laden tissue-engineered constructs with high cell viability. , 2014, Biomaterials.