Pancreatic extracellular matrix and platelet‐rich plasma constructing injectable hydrogel for pancreas tissue engineering

Abstract

The development of pancreatic extracellular matrices enriched with insulin-secreting β-cells is a promising tissue engineering approach to treat type 1 diabetes. However, its long-term therapeutic efficacy is restricted by the defensive mechanism of host immune response and the lack of developed vascularization as appropriate after transplantation. Platelet-rich plasma (PRP), as an autologous platelet concentrate, contains a large number of active factors that are essential for the cell viability, vascularization, and immune regulation. In this study, we have incorporated pancreatic extracellular matrix (PEM) with PRP to develop a three-dimensional (3D) injectable PEM-PRP hydrogel to coculture and transplant rat insulinoma cells (INS-1) and human umbilical vein endothelial cells (HUVECs). Results from this study demonstrated that PEM-PRP hydrogel mimicked the biochemical compositions of native extracellular matrices, and possessed the enhanced elastic modulus and resistance to enzymatic degradation that enabled biomaterials to maintain its volume and slowly degrade. Additionally, PEM-PRP hydrogel could release growth factors in a sustained manner. In vitro, PEM-PRP hydrogel significantly promoted the viability, insulin-secreting function, and insulin gene expression of gel encapsulated INS-1 cells. Moreover, HUVECs encapsulated in PEM-PRP hydrogel were found to constitute many lumen-like structures and exhibited high expression of proangiogenic genes. In vivo transplantation of PEM-PRP hydrogel encapsulated with INS-1 cells and HUVECs improved the viability of INS-1 cells, promoted vascularization, inhibited the host inflammatory response, and reversed hyperglycemia of diabetic rats. Our study suggests that the PEM-PRP hydrogel offers excellent biocompatibility and proangiogenic property, and may serve as an effective biomaterial platform to maintain the long-term survival and function of insulin-secreting β cells.

Viability and Functionality of Neonatal Porcine Islet-like Cell Clusters Bioprinted in Alginate-Based Bioinks

“…A positive effect on the number of β-cells was also observed when PRP was added during the differentiation of induced pluripotent stem cells [ 63 ]. When PRP was used in combination with biomaterials, specifically alginate and decellularized pancreatic extracellular matrix (dECM), this resulted in an improved viability, a higher insulin gene expression, and a higher insulin release from β-cell lines [ 64 , 65 ]. In the present study, we used platelet lysate produced from PRP.…”

“…Furthermore, only supplementation with FFP resulted in fewer apoptotic nuclei from day 7 onwards and a higher proliferation until day 7. In contrast to this, in vitro other groups observed a definitive increase in the viability of murine islets after the addition of serum albumin to alginate [ 39 ], an increased viability of β-cell lines when PRP was added to alginate [ 64 ] or to pancreatic dECM [ 65 ], and an increased viability of murine islets when PRP was added to the culture medium [ 59 ]. Of these, only the study by Schneider et al with albumin-supplemented alginate analysed a time frame of more than one week [ 39 ], whereas the effect seen in the in vitro studies with PRP [ 59 , 64 , 65 ] was reported for a maximum of 5 days.…”

“…However, in contrast to reports by other groups, in the present study, supplementation of bioinks did not further increase insulin secretion in a notable fashion. On the other hand, only a low number of studies with serum albumin have been performed [ 39 ] and when PRP was used it was either a short time of observation [ 59 , 64 , 65 ], or repeated supplementation [ 40 , 41 ].…”

Human umbilical cord platelet-rich plasma to treat endometrial pathologies: methodology, composition and pre-clinical models

“…Uteri from healthy sows were processed as we previously described ( López-Martínez et al , 2021a ), to produce the EndoECM, in accordance with ISO 9001 quality management, in relation to the safe and legal procurement of animal organs from the slaughterhouse. Then, as established in other studies using extracellular matrix hydrogels ( Zhang et al , 2020a ), 15% (v/v) of thawed hUC-PRP was supplemented in 6 mg/ml of EndoECM to prepare the EndoECM + hUC-PRP treatment.…”

A novel hybrid polymer of PCL/fish gelatin nanofibrous scaffold improves proliferation and differentiation of Wharton's jelly‐derived mesenchymal cells into islet‐like cells

“…Moreover, using 3D culture in stem cell biology increases cell-cell and cell-matrix interactions and enables cell signaling by emulating in vivo environment. 14 In addition, 3D nanofibers can provide direct interaction with diverse ECM components such as biomolecules, molecular signaling, and growth factors. 15,16 Hence, 3D culture ameliorates the differentiation of diverse kinds of cells into IPCs compared to those differentiated in 2D culture.…”