Assessment of Angiogenesis and Cell Survivability of an Inkjet Bioprinted Biological Implant in an Animal Model

Abstract

The rapidly growing field of tissue engineering hopes to soon address the shortage of transplantable tissues, allowing for precise control and fabrication that could be made for each specific patient. The protocols currently in place to print large-scale tissues have yet to address the main challenge of nutritional deficiencies in the central areas of the engineered tissue, causing necrosis deep within and rendering it ineffective. Bioprinted microvasculature has been proposed to encourage angiogenesis and facilitate the mobility of oxygen and nutrients throughout the engineered tissue. An implant made via an inkjet printing process containing human microvascular endothelial cells was placed in both B17-SCID and NSG-SGM3 animal models to determine the rate of angiogenesis and degree of cell survival. The implantable tissues were made using a combination of alginate and gelatin type B; all implants were printed via previously published procedures using a modified HP inkjet printer. Histopathological results show a dramatic increase in the average microvasculature formation for mice that received the printed constructs within the implant area when compared to the manual and control implants, indicating inkjet bioprinting technology can be effectively used for vascularization of engineered tissues.

Bioengineering Cell Therapy for Treatment of Peripheral Artery Disease

“…The orifice of the inkjet print head allows single cells to pass through after being subjected to high-energy sources (Figure 2B). 84 Thermal inkjet printing was the first technology that was used for bioengineering applications with protein arrays and DNA chips as the first bioprinting products. [87][88][89] Following these successes, printing bacteria and mammalian cells with high viability rates paved the way for a wider range of applications.…”

“…[87][88][89] Following these successes, printing bacteria and mammalian cells with high viability rates paved the way for a wider range of applications. 90 For example, Oropeza et al 84 demonstrated the ability to print human microvascular ECs using a modified inkjet bioprinter and successfully implanted the constructs into a murine model, resulting in a significant increase in the vascular formations in the implant area (Figure 2C). 91 Advances in 3D printing have led to the development of new approaches to treat PAD, specifically in generating large tissue-engineered vascular graft replacements.…”

“…CD31 indicates cluster of differentiation 31; CMU, Carnegie Mellon University; HMVEC-D, human dermal microvascular endothelial cells; P, pressure; and rhCOllagen, recombinant human collagen. B and C , Adapted from Oropeza et al 84 D and E , Adapted from Hinton et al 85 F and G , Adapted from Szklanny et al 86 with permission. Copyright ©2021, John Wiley and Sons.…”

Inkjet Printing of Pharmaceuticals

“…In an innovative approach, the utilization of bioprinted microvasculature has been suggested as a means to foster angiogenesis and enhance the diffusion of essential oxygen and nutrients throughout engineered tissue constructs. [ 213 ] An implant, created using thermal IJP, featured HMVECs and was strategically placed within both CB17severe combined immunodeficient (CB‐17 SCID; i.e., strain bred mice that lack functional T and B cells) and NSG‐SGM3 (i.e., non‐obese diabetic SCID gamma mice with human stem cell factor, granulocyte macrophage colony stimulating factor and interleukin‐3) animal models. This strategic positioning aimed to assess the kinetics of angiogenesis and the extent of cell viability.…”