The New Frontiers of Artificial Organs Engineering

A special issue of Bioengineering (ISSN 2306-5354). This special issue belongs to the section "Regenerative Engineering".

Deadline for manuscript submissions: closed (31 December 2024) | Viewed by 24868

Special Issue Editors


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Guest Editor
Faculty of Engineering, University Campus Biomedico of Rome, Rome, Italy
Interests: artificial organs; transport phenomena; biochemical reactors
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Guest Editor
Computer Systems and Bioinformatics Lab, Università Campus Bio-Medico di Roma, Via Alvaro del Portillo 21, 00128 Roma, Italy
Interests: AI; machine learning; deep neural networks
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Research in the field of artificial organs and regenerative medicine is currently encouraging the flourishing production of promising results regarding the application of novel technologies to the development of artificial and bioartificial organs (kidney, liver, lung, pancreas, intestine, etc.). The introduction of novel materials, microfabrication technologies, and advanced computational methodologies is revealing novel biological mechanisms in cell and tissue behavior and opening new avenues in the development of artificial and bioartificial organs. These innovations hold promise for the treatment of several life-threatening diseases, and the clinical translational inspiration of research in this field is additionally stimulating to foster scientific discussion.

This Special Issue will focus on the recent developments of bioengineering sciences in the field of artificial and bioartificial organs (ABOs).

The journal will be accepting contributions (both original articles and reviews) mainly centered on the following topics:

  • Computational methods for ABOs;
  • Transport phenomena in ABOs;
  • Bioreactors for bioartificial organs;
  • Cell culture for bioartificial organs;
  • Microfabrication technologies for ABOs;
  • Membrane applications in ABOs.

Prof. Dr. Piemonte Vincenzo
Dr. Mario Merone
Guest Editors

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Keywords

  • Computational methods
  • Transport phenomena
  • Bioreactors
  • Membranes
  • Cell culture
  • Microfabrication

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Published Papers (9 papers)

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Research

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15 pages, 6856 KiB  
Article
Decellularization of Human Digits: A Step Towards Off-the-Shelf Composite Allograft Transplantation
by Michelle E. McCarthy, Irina Filz von Reiterdank, Oliver H. Parfitt van Pallandt, McLean S. Taggart, Laura Charlès, Korkut Uygun, Alexandre G. Lellouch, Curtis L. Cetrulo, Jr. and Basak E. Uygun
Bioengineering 2025, 12(4), 383; https://doi.org/10.3390/bioengineering12040383 - 3 Apr 2025
Viewed by 297
Abstract
The field of reconstructive surgery faces significant challenges in addressing limb loss and disfigurement, with current organ preservation methods limited by short storage times. Decellularization offers a promising solution for generating engineered alternatives for reconstructive surgery by removing cellular material while preserving the [...] Read more.
The field of reconstructive surgery faces significant challenges in addressing limb loss and disfigurement, with current organ preservation methods limited by short storage times. Decellularization offers a promising solution for generating engineered alternatives for reconstructive surgery by removing cellular material while preserving the extracellular matrix (ECM) and providing scaffolds for tissue regeneration. In this study, we developed a robust protocol for decellularizing whole digits from long-term freezer storage, achieving the successful removal of cellular material with intact ECM. Digit angiography confirmed the preservation of vascular integrity, facilitating future perfusion for recellularization. Quantitative analysis revealed significantly lower DNA content in decellularized tissues, indicating effective decellularization. Furthermore, extracellular matrix analysis showed the preservation of collagen, elastin, and glycosaminoglycans (GAGs) contents. Histological examination confirmed the reduction in cellularity and maintenance of tissue architecture in decellularized digits. Mechanical strength testing of decellularized digit tendons proved consistent with that of native digits. Our findings highlight the potential of decellularized digits as versatile platforms for tissue engineering and regenerative medicine. Moving forward, further optimization of protocols and collaborative efforts are essential for translating these findings into clinical practice, offering innovative solutions for reconstructive surgery and limb transplantation. Full article
(This article belongs to the Special Issue The New Frontiers of Artificial Organs Engineering)
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12 pages, 2200 KiB  
Article
A 3D Printing-Based Transcatheter Pulmonary Valve Replacement Simulator: Development and Validation
by Yuanzhang Liu, Yu Mao, Yiwei Wang, Ping Jin, Mengen Zhai, Yang Liu and Jian Yang
Bioengineering 2025, 12(4), 344; https://doi.org/10.3390/bioengineering12040344 - 26 Mar 2025
Viewed by 186
Abstract
Background: Severe pulmonary regurgitation (PR) often occurs after treatment of tetralogy of Fallot with a valve ring patch, leading to enlargement and diverse morphological characteristics of the native right ventricular outflow tract (nRVOT), which increases the difficulty of transcatheter pulmonary valve replacement (TPVR). [...] Read more.
Background: Severe pulmonary regurgitation (PR) often occurs after treatment of tetralogy of Fallot with a valve ring patch, leading to enlargement and diverse morphological characteristics of the native right ventricular outflow tract (nRVOT), which increases the difficulty of transcatheter pulmonary valve replacement (TPVR). The purpose of this study was to use the TPVR simulator to help doctors improve their surgical skills by simulating the surgical process in vitro. Methods: The TPVR simulator was developed using three-dimensional (3D) printing technology under computer-aided design. In this study, the TPVR simulator was used for preoperative simulation training and teaching. First, 10 specialists were equally divided into a 3D-printed group and a non-3D-printed group, each performing one TPVR; then, another six specialists and six young surgeons were selected to complete three TPVR simulations. Results: For the 3D-printed simulation group, the over-flap time (5.22 min (range: 4.85–5.87 min) vs. 6.72 min (range: 6.12–7.70 min), p = 0.016), fluoroscopy time (15.00 min (range: 13.50–16.50 min) vs. 19.00 min (range: 17.50–21.50 min), p = 0.012), and total operative time for the five surgeons (57.00 min (range: 54.00–62.50 min) vs. 67.00 min (range: 62.00–69.50 min), p = 0.036) were shorter. In addition, the results showed significant reductions in the median over-flap time and total time required in both the expert panel and young surgeon groups (all p < 0.05). Conclusions: The reliability and validity of the TPVR simulator was initially demonstrated and has the potential to be a teaching and training tool for surgeons. Full article
(This article belongs to the Special Issue The New Frontiers of Artificial Organs Engineering)
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12 pages, 3813 KiB  
Article
Exploring the Role of Desmoplastic Physical Stroma in Pancreatic Cancer Progression Using a Three-Dimensional Collagen Matrix Model
by Xiaoyu Song, Yuma Nihashi, Masamichi Yamamoto, Daiki Setoyama, Yuya Kunisaki and Yasuyuki S. Kida
Bioengineering 2023, 10(12), 1437; https://doi.org/10.3390/bioengineering10121437 - 18 Dec 2023
Cited by 1 | Viewed by 2250
Abstract
Pancreatic ductal adenocarcinoma (PDAC) is a refractory tumor with a poor prognosis, and its complex microenvironment is characterized by a fibrous interstitial matrix surrounding PDAC cells. Type I collagen is a major component of this interstitial matrix. Abundant type I collagen promotes its [...] Read more.
Pancreatic ductal adenocarcinoma (PDAC) is a refractory tumor with a poor prognosis, and its complex microenvironment is characterized by a fibrous interstitial matrix surrounding PDAC cells. Type I collagen is a major component of this interstitial matrix. Abundant type I collagen promotes its deposition and cross-linking to form a rigid and dense physical barrier, which limits drug penetration and immune cell infiltration and provides drug resistance and metabolic adaptations. In this study, to identify the physical effect of the stroma, type I collagen was used as a 3D matrix to culture Capan-1 cells and generate a 3D PDAC model. Using transcriptome analysis, a link between type I collagen-induced physical effects and the promotion of Capan-1 cell proliferation and migration was determined. Moreover, metabolomic analysis revealed that the physical effect caused a shift in metabolism toward a glycolytic phenotype. In particular, the high expression of proline in the metabolites suggests the ability to maintain Capan-1 cell proliferation under hypoxic and nutrient-depleted conditions. In conclusion, we identified type I collagen-induced physical effects in promoting Capan-1 cells, which cause PDAC progression, providing support for the role of dense stroma in the PDAC microenvironment and identifying a fundamental method for modeling the complex PDAC microenvironment. Full article
(This article belongs to the Special Issue The New Frontiers of Artificial Organs Engineering)
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13 pages, 4412 KiB  
Article
Modeling and Validation of an Ultra-Compact Regenerative Liver Dialysis Device
by Tamara Boscarino, Leone Mazzeo, Franca Abbruzzese, Mario Merone and Vincenzo Piemonte
Bioengineering 2023, 10(6), 706; https://doi.org/10.3390/bioengineering10060706 - 11 Jun 2023
Viewed by 1623
Abstract
The availability of a wearable artificial liver that facilitates extracorporeal dialysis outside of medical facilities would represent a significant advancement for patients requiring dialysis. The objective of this preliminary investigation is to explore, using validated mathematical models based on in vitro data, the [...] Read more.
The availability of a wearable artificial liver that facilitates extracorporeal dialysis outside of medical facilities would represent a significant advancement for patients requiring dialysis. The objective of this preliminary investigation is to explore, using validated mathematical models based on in vitro data, the feasibility of developing a novel, cost-effective, and highly compact extracorporeal liver support device that can be employed as a transitional therapy to transplantation outside of clinical settings. Such an innovation would offer substantial cost savings to the national healthcare system while significantly improving the patient’s quality of life. The experimental components consisted of replacing traditional adsorbent materials with albumin-functionalized silica microspheres due to their capacity to adsorb bilirubin, one of the toxins responsible for liver failure. Two configurations of the dialysis module were tested: one involved dispersing the adsorbent particles in dialysis fluid, while the other did not require dialysis fluid. The results demonstrate the superior performance of the first configuration compared to the second. Although the clinical applicability of these models remains distant from the current stage, further studies will focus on optimizing these models to develop a more compact and wearable device. Full article
(This article belongs to the Special Issue The New Frontiers of Artificial Organs Engineering)
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11 pages, 459 KiB  
Article
Blood Glucose Level Forecasting on Type-1-Diabetes Subjects during Physical Activity: A Comparative Analysis of Different Learning Techniques
by Benedetta De Paoli, Federico D’Antoni, Mario Merone, Silvia Pieralice, Vincenzo Piemonte and Paolo Pozzilli
Bioengineering 2021, 8(6), 72; https://doi.org/10.3390/bioengineering8060072 - 26 May 2021
Cited by 12 | Viewed by 4137
Abstract
Background: Type 1 Diabetes Mellitus (T1DM) is a widespread chronic disease in industrialized countries. Preventing blood glucose levels from exceeding the euglycaemic range would reduce the incidence of diabetes-related complications and improve the quality of life of subjects with T1DM. As a consequence, [...] Read more.
Background: Type 1 Diabetes Mellitus (T1DM) is a widespread chronic disease in industrialized countries. Preventing blood glucose levels from exceeding the euglycaemic range would reduce the incidence of diabetes-related complications and improve the quality of life of subjects with T1DM. As a consequence, in the last decade, many Machine Learning algorithms aiming to forecast future blood glucose levels have been proposed. Despite the excellent performance they obtained, the prediction of abrupt changes in blood glucose values produced during physical activity (PA) is still one of the main challenges. Methods: A Jump Neural Network was developed in order to overcome the issue of predicting blood glucose values during PA. Three learning configurations were developed and tested: offline training, online training, and online training with reinforcement. All configurations were tested on six subjects suffering from T1DM that held regular PA (three aerobic and three anaerobic) and exploited Continuous Glucose Monitoring (CGM). Results: The forecasting performance was evaluated in terms of the Root-Mean-Squared-Error (RMSE), according to a paradigm of Precision Medicine. Conclusions: The online learning configurations performed better than the offline configuration in total days but not on the only CGM associated with the PA; thus, the results do not justify the increased computational burden because the improvement was not significant. Full article
(This article belongs to the Special Issue The New Frontiers of Artificial Organs Engineering)
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Review

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20 pages, 318 KiB  
Review
Narrative Review and Guide: State of the Art and Emerging Opportunities of Bioprinting in Tissue Regeneration and Medical Instrumentation
by Jaroslava Halper
Bioengineering 2025, 12(1), 71; https://doi.org/10.3390/bioengineering12010071 - 15 Jan 2025
Viewed by 1218
Abstract
Three-dimensional printing was introduced in the 1980s, though bioprinting started developing a few years later. Today, 3D bioprinting is making inroads in medical fields, including the production of biomedical supplies intended for internal use, such as biodegradable staples. Medical bioprinting enables versatility and [...] Read more.
Three-dimensional printing was introduced in the 1980s, though bioprinting started developing a few years later. Today, 3D bioprinting is making inroads in medical fields, including the production of biomedical supplies intended for internal use, such as biodegradable staples. Medical bioprinting enables versatility and flexibility on demand and is able to modify and individualize production using several established printing methods. A great selection of biomaterials and bioinks is available, including natural, synthetic, and mixed options; they are biocompatible and non-toxic. Many bioinks are biodegradable and they accommodate cells so upon implantation, they integrate within the new environment. Bioprinting is suitable for printing tissues using living or viable components, such as collagen scaffolding, cartilage components, and cells, and also for printing parts of structures, such as teeth, using artificial man-made materials that will become embedded in vivo. Bioprinting is an integral part of tissue engineering and regenerative medicine. The addition of newly developed smart biomaterials capable of incorporating dynamic changes in shape depending on the nature of stimuli led to the addition of the fourth dimension of time in the form of changing shape to the three static dimensions. Four-dimensional bioprinting is already making significant inroads in tissue engineering and regenerative medicine, including new ways to create dynamic tissues. Its future lies in constructing partial or whole organ generation. Full article
(This article belongs to the Special Issue The New Frontiers of Artificial Organs Engineering)
26 pages, 1912 KiB  
Review
Control of Blood Coagulation by Hemocompatible Material Surfaces—A Review
by Janna Kuchinka, Christian Willems, Dmitry V. Telyshev and Thomas Groth
Bioengineering 2021, 8(12), 215; https://doi.org/10.3390/bioengineering8120215 - 15 Dec 2021
Cited by 68 | Viewed by 8587
Abstract
Hemocompatibility of biomaterials in contact with the blood of patients is a prerequisite for the short- and long-term applications of medical devices such as cardiovascular stents, artificial heart valves, ventricular assist devices, catheters, blood linings and extracorporeal devices such as artificial kidneys (hemodialysis), [...] Read more.
Hemocompatibility of biomaterials in contact with the blood of patients is a prerequisite for the short- and long-term applications of medical devices such as cardiovascular stents, artificial heart valves, ventricular assist devices, catheters, blood linings and extracorporeal devices such as artificial kidneys (hemodialysis), extracorporeal membrane oxygenation (ECMO) and cardiopulmonary bypass. Although lower blood compatibility of materials and devices can be handled with systemic anticoagulation, its side effects, such as an increased bleeding risk, make materials that have a better hemocompatibility highly desirable, particularly in long-term applications. This review provides a short overview on the basic mechanisms of blood coagulation including plasmatic coagulation and blood platelets, as well as the activation of the complement system. Furthermore, a survey on concepts for tailoring the blood response of biomaterials to improve the hemocompatibility of medical devices is given which covers different approaches that either inhibit interaction of material surfaces with blood components completely or control the response of the coagulation system, blood platelets and leukocytes. Full article
(This article belongs to the Special Issue The New Frontiers of Artificial Organs Engineering)
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Other

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9 pages, 847 KiB  
Perspective
Towards a Better Understanding of the Human Health Risk of Per- and Polyfluoroalkyl Substances Using Organoid Models
by Haoan Xu, Jiahui Kang, Xue Gao, Yingying Lan and Minghui Li
Bioengineering 2025, 12(4), 393; https://doi.org/10.3390/bioengineering12040393 - 7 Apr 2025
Viewed by 341
Abstract
The ubiquitous presence of per- and polyfluoroalkyl substances (PFAS) in the environment has garnered global public concern. Epidemiological studies have proved that exposure to PFAS is associated with human health risks. Although evidence demonstrated the toxic mechanisms of PFAS based on animal models [...] Read more.
The ubiquitous presence of per- and polyfluoroalkyl substances (PFAS) in the environment has garnered global public concern. Epidemiological studies have proved that exposure to PFAS is associated with human health risks. Although evidence demonstrated the toxic mechanisms of PFAS based on animal models and traditional cell cultures, their limitations in inter-species differences and lack of human-relevant microenvironments hinder the understanding of health risks from PFAS exposure. There is an increasing necessity to explore alternative methodologies that can effectively evaluate human health risks. Human organoids derived from stem cells accurately mimic the sophisticated and multicellular structures of native human organs, providing promising models for toxicology research. Advanced organoids combined with innovative technologies are expected to improve understanding of the breadth and depth of PFAS toxicity. Full article
(This article belongs to the Special Issue The New Frontiers of Artificial Organs Engineering)
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5 pages, 898 KiB  
Case Report
Success of Thrombectomy in Management of Ischemic Stroke in Two Patients with SynCardia Total Artificial Heart in Bridge-to-Transplantation
by Brendan Le Picault, Charles-Henri David, Pierre-Louis Alexandre, Cédric Lenoble, Philippe Bizouarn, Thierry Lepoivre, Nicolas Groleau, Bertrand Rozec, Hubert Desal, Jean-Christian Roussel and Thomas Sénage
Bioengineering 2021, 8(9), 126; https://doi.org/10.3390/bioengineering8090126 - 19 Sep 2021
Cited by 2 | Viewed by 3913
Abstract
Introduction: Circulatory assistance from a SynCardia Total Artificial Heart (SynCardia-TAH) is a reliable bridge-to-transplant solution for patients with end-stage biventricular heart failure. Ischemic strokes affect about 10% of patients with a SynCardia-TAH. We report for the first time in the literature two successful [...] Read more.
Introduction: Circulatory assistance from a SynCardia Total Artificial Heart (SynCardia-TAH) is a reliable bridge-to-transplant solution for patients with end-stage biventricular heart failure. Ischemic strokes affect about 10% of patients with a SynCardia-TAH. We report for the first time in the literature two successful thrombectomies to treat the acute phase of ischemic stroke in two patients treated with a SynCardia-TAH in the bridge-to-transplant (BTT). Case report: We follow two patients with circulatory support from a SynCardia-TAH in the bridge-to-transplant for terminal biventricular cardiac failure with ischemic stroke during the support period. An early in-hospital diagnosis enables the completion of a mechanical thrombectomy within the first 6 h of the onset of symptoms. There was no intracranial hemorrhagic complication during or after the procedure and the patients fully recovered from neurological deficits, allowing a successful heart transplant. Conclusion: This case report describes the possibility of treating ischemic strokes under a SynCardia-TAH by mechanical thrombectomy following the same recommendations as for the general population with excellent results and without any hemorrhagic complication during or after the procedure. Full article
(This article belongs to the Special Issue The New Frontiers of Artificial Organs Engineering)
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