Tissue printing for engineering transplantable human parathyroid patch to improve parathyroid engraftment, integration, and hormone secretion in vivo

Abstract

During thyroid surgery, some parathyroid glands fail to maintain their function, therefore, they are unavoidably detached from the patient. For the purpose of re-preservation of the function, they are minced into small segments and transplanted into the fat or muscle layer. Yet, this method of auto-grafting the parathyroid glands is frequently unsuccessful due to its poor interaction and engraftment with the native tissue, eventually leading to the dysfunction of the parathyroid hormone (PTH) secretion. In this study, we suggest a methodology to restore parathyroid activity through the introduction of the ‘tissue printing’ concept. Parathyroid glands of patients with secondary hyperparathyroidism were minced into the fragments smaller than 0.5 × 0.5 mm, which is in common with the traditional surgical method. These parathyroid tissues (PTs) were uniformly mixed with the adipose-derived decellularized extracellular matrix (adECM) bioink that protects the PTs from hostile in vivo environments and promote initial engraftment. PTs-encapsulated adECM bioink (PTs-adECM) was then printed onto the pre-designed polycaprolactone (PCL) mesh to produce patch-type PTs construct, which functions as a mechanical support to further enhance long-term in vivo stability. The engineered patch was transplanted subcutaneously into rats and harvested after 4 weeks. In vivo results showed that the engineered patches were well engrafted and stabilized in their original position for 4 weeks as compared with PTs only. Immunohistochemistry results further revealed that the concentration of PTH was approximately 2.5-fold greater in rats engrafted in the patch. Taken together, we envision that the novel concept ‘tissue printing’ over cell printing could provide a closer step towards clinical applications of 3D bioprinting to solve the unmet need for parathyroid surgery method.