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Bioengineering
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Tissue Engineering Scaffolds in Regenerative Medicine
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Tissue Engineering Scaffolds in Regenerative Medicine

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

Deadline for manuscript submissions: closed (31 October 2024) | Viewed by 11188

Special Issue Editors

Dr. Kamol Dey

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Guest Editor
Department of Applied Chemistry and Chemical Engineering, Faculty of Science, University of Chittagong, Chittagong 4331, Bangladesh
Interests: biomaterials; biopolymers; biomimetic hydrogels; nanocomposites; tissue engineering
Prof. Dr. Barbara Nebe

E-Mail Website
Guest Editor
Department of Cell Biology, Rostock University Medical Center, University of Rostock, 18059 Rostock, Germany
Interests: cell–material interaction; osteoblasts; epithelial cells; calcium signaling; cell adhesion; cell cycle and apoptosis; focal adhesions; cellular structures; physico-chemical characteristics of biomaterials; micro-topography
Special Issues, Collections and Topics in MDPI journals
Prof. Dr. Luciana Sartore

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Guest Editor
Department of Mechanical and Industrial Engineering, University of Brescia, Via Branze 38, 25123 Brescia, Italy
Interests: Polymer science; Materials science and technology; Biomaterials; Hydrogels; Tissue engineering

Special Issue Information

Dear Colleagues,

The Fourth Industrial Revolution (4IR) is transforming health and healthcare system to become much more connected, precise, and democratized through medical and technological breakthroughs. Though great progress has been made in medicine over the years, however, current clinical approaches are not enough to meet a significant number of clinical disorders due to disease, trauma, congenital abnormalities, or ageing. For instance, everyday thousands of people of all ages across the world are admitted to hospitals because of the severe injuries or malfunction of some vital organs. Organ or tissue transplantation is a standard therapy to treat these patients. Irony of fact that many of these people will die due to the paucity of donor organs and high processing cost involved in organ transplantation. In this regard, tissue engineering and regenerative medicine (TERM) is a game-changing area of medicine with the potential to fully heal damaged tissues and organs and is promoting the move towards “cells as pills”. Tissue engineering scaffolds – that mimic the native extracellular matrix (ECM) - play a vital role in providing an environment that facilitates cellular growth, differentiation, and maturation. However, it’s still a critical engineering challenge to design clinically relevant scaffolds in a congenial and sustainable approach. Moreover, we know little how mechanical properties of the scaffolds regulate various cellular processes such as cell division, stem cell differentiation and cancer progression. In this special issue of Bioengineering on Tissue Engineering Scaffolds in Regenerative Medicine, we invite experts worldwide to submit contributions that provide novel findings in the field of scaffold-based tissue engineering and regenerative medicine. We welcome results from basic research, preclinical, or clinical research and reviews that highlight new findings on scaffold design for tissue regeneration and regenerative medicine, 3D printing of scaffolds, clinical translation of scaffolds, and mechanotransduction.   

Dr. Kamol Dey
Prof. Dr. Barbara Nebe
Prof. Dr. Luciana Sartore
Guest Editors

Manuscript Submission Information

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Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Bioengineering is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • biomaterials
  • scaffolds design
  • tunable scaffold performance
  • additive manufacturing
  • physico-chemical modifications
  • mechanotransduction
  • chondrogenesis
  • osteogenesis
  • tissue engineering and regenerative medicine

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Published Papers (6 papers)

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Research

18 pages, 2504 KiB  
Article
Bovine Placentome-Derived Extracellular Matrix: A Sustainable 3D Scaffold for Cultivated Meat
by Cemile Bektas, Kathleen Lee, Anisha Jackson, Mohit Bhatia and Yong Mao
Bioengineering 2024, 11(8), 854; https://doi.org/10.3390/bioengineering11080854 - 21 Aug 2024
Viewed by 1406
Abstract
Cultivated meat, an advancement in cellular agriculture, holds promise in addressing environmental, ethical, and health challenges associated with traditional meat production. Utilizing tissue engineering principles, cultivated meat production employs biomaterials and technologies to create cell-based structures by introducing cells into a biocompatible scaffold, [...] Read more.
Cultivated meat, an advancement in cellular agriculture, holds promise in addressing environmental, ethical, and health challenges associated with traditional meat production. Utilizing tissue engineering principles, cultivated meat production employs biomaterials and technologies to create cell-based structures by introducing cells into a biocompatible scaffold, mimicking tissue organization. Among the cell sources used for producing muscle-like tissue for cultivated meats, primary adult stem cells like muscle satellite cells exhibit robust capabilities for proliferation and differentiation into myocytes, presenting a promising avenue for cultivated meat production. Evolutionarily optimized for growth in a 3D microenvironment, these cells benefit from the biochemical and biophysical cues provided by the extracellular matrix (ECM), regulating cell organization, interactions, and behavior. While plant protein-based scaffolds have been explored for their utilization for cultivated meat, they lack the biological cues for animal cells unless functionalized. Conversely, a decellularized bovine placental tissue ECM, processed from discarded birth tissue, achieves the biological functionalities of animal tissue ECM without harming animals. In this study, collagen and total ECM were prepared from decellularized bovine placental tissues. The collagen content was determined to be approximately 70% and 40% in isolated collagen and ECM, respectively. The resulting porous scaffolds, crosslinked through a dehydrothermal (DHT) crosslinking method without chemical crosslinking agents, supported the growth of bovine myoblasts. ECM scaffolds exhibited superior compatibility and stability compared to collagen scaffolds. In an attempt to make cultivate meat constructs, bovine myoblasts were cultured in steak-shaped ECM scaffolds for about 50 days. The resulting construct not only resembled muscle tissues but also displayed high cellularity with indications of myogenic differentiation. Furthermore, the meat constructs were cookable and able to sustain the grilling/frying. Our study is the first to utilize a unique bovine placentome-derived ECM scaffold to create a muscle tissue-like meat construct, demonstrating a promising and sustainable option for cultivated meat production. Full article
(This article belongs to the Special Issue Tissue Engineering Scaffolds in Regenerative Medicine)
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13 pages, 4336 KiB  
Article
Nerve Reconstruction Using ActiGraft Blood Clot in Rabbit Acute Peripheral Injury Model: Preliminary Study
by Shimon Rochkind, Sharon Sirota and Alon Kushnir
Bioengineering 2024, 11(4), 298; https://doi.org/10.3390/bioengineering11040298 - 22 Mar 2024
Viewed by 1377
Abstract
This preliminary study aimed to investigate an ActiGraft blood clot implant (RedDress Ltd., Pardes-Hanna, Israel) attempting to treat and induce the regeneration of a completely injured peripheral nerve with a massive loss defect. The tibial portion of the sciatic nerve in 11 rabbits [...] Read more.
This preliminary study aimed to investigate an ActiGraft blood clot implant (RedDress Ltd., Pardes-Hanna, Israel) attempting to treat and induce the regeneration of a completely injured peripheral nerve with a massive loss defect. The tibial portion of the sciatic nerve in 11 rabbits was transected, and a 25 mm nerve gap was reconnected using a collagen tube. A comparison was performed between the treatment group (eight rabbits; reconnection using a tube filled with ActiGraft blood clot) and the control group (three rabbits; gap reconnection using an empty tube). The post-operative follow-up period lasted 18 weeks and included electrophysiological and histochemical assessments. The pathological severity score was high in the tube cross sections of the control group (1.33) compared to the ActiGraft blood clot treatment group (0.63). Morphometric analysis showed a higher percentage of the positive myelin basic protein (MBP) stained area in the ActiGraft blood clot group (19.57%) versus the control group (3.67%). These differences were not statistically significant due to the small group sizes and the large intra-group variability. The results of this preliminary study suggest that the application of an ActiGraft blood clot (into the collagen tube) can enable nerve recovery. However, a future study using a larger animal group is required to achieve objective statistical results. Full article
(This article belongs to the Special Issue Tissue Engineering Scaffolds in Regenerative Medicine)
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16 pages, 3387 KiB  
Article
Unlocking the Promise of Decellularized Pancreatic Tissue: A Novel Approach to Support Angiogenesis in Engineered Tissue
by Lei Hao, Fariba Khajouei, Jaselin Rodriguez, Soojin Kim and Eun Jung A. Lee
Bioengineering 2024, 11(2), 183; https://doi.org/10.3390/bioengineering11020183 - 14 Feb 2024
Cited by 1 | Viewed by 2216
Abstract
Advancements in regenerative medicine have highlighted the potential of decellularized extracellular matrix (ECM) as a scaffold for organ bioengineering. Although the potential of ECM in major organ systems is well-recognized, studies focusing on the angiogenic effects of pancreatic ECM are limited. This study [...] Read more.
Advancements in regenerative medicine have highlighted the potential of decellularized extracellular matrix (ECM) as a scaffold for organ bioengineering. Although the potential of ECM in major organ systems is well-recognized, studies focusing on the angiogenic effects of pancreatic ECM are limited. This study investigates the capabilities of pancreatic ECM, particularly its role in promoting angiogenesis. Using a Triton-X-100 solution, porcine pancreas was successfully decellularized, resulting in a significant reduction in DNA content (97.1% removal) while preserving key pancreatic ECM components. A three-dimensional ECM hydrogel was then created from this decellularized tissue and used for cell culture. Biocompatibility tests demonstrated enhanced adhesion and proliferation of mouse embryonic stem cell-derived endothelial cells (mES-ECs) and human umbilical vein endothelial cells (HUVECs) in this hydrogel compared to conventional scaffolds. The angiogenic potential was evaluated through tube formation assays, wherein the cells showed superior tube formation capabilities in ECM hydrogel compared to rat tail collagen. The RT-PCR analysis further confirmed the upregulation of pro-angiogenic genes in HUVECs cultured within the ECM hydrogel. Specifically, HUVECs cultured in the ECM hydrogel exhibited a significant upregulation in the expression of MMP2, VEGF and PAR-1, compared to those cultured in collagen hydrogel or in a monolayer condition. The identification of ECM proteins, specifically PRSS2 and Decorin, further supports the efficacy of pancreatic ECM hydrogel as an angiogenic scaffold. These findings highlight the therapeutic promise of pancreatic ECM hydrogel as a candidate for vascularized tissue engineering application. Full article
(This article belongs to the Special Issue Tissue Engineering Scaffolds in Regenerative Medicine)
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22 pages, 4893 KiB  
Article
Optimizing Bioink Composition for Human Chondrocyte Expression of Lubricin
by Kari Martyniak, Sean Kennedy, Makan Karimzadeh, Maria A. Cruz, Oju Jeon, Eben Alsberg and Thomas J. Kean
Bioengineering 2023, 10(9), 997; https://doi.org/10.3390/bioengineering10090997 - 23 Aug 2023
Cited by 3 | Viewed by 2051
Abstract
The surface zone of articular cartilage is the first area impacted by cartilage defects, commonly resulting in osteoarthritis. Chondrocytes in the surface zone of articular cartilage synthesize and secrete lubricin, a proteoglycan that functions as a lubricant protecting the deeper layers from shear [...] Read more.
The surface zone of articular cartilage is the first area impacted by cartilage defects, commonly resulting in osteoarthritis. Chondrocytes in the surface zone of articular cartilage synthesize and secrete lubricin, a proteoglycan that functions as a lubricant protecting the deeper layers from shear stress. Notably, 3D bioprinting is a tissue engineering technique that uses cells encapsulated in biomaterials to fabricate 3D constructs. Gelatin methacrylate (GelMA) is a frequently used biomaterial for 3D bioprinting cartilage. Oxidized methacrylated alginate (OMA) is a chemically modified alginate designed for its tunable degradation rate and mechanical properties. To determine an optimal combination of GelMA and OMA for lubricin expression, we used our novel high-throughput human articular chondrocyte reporter system. Primary human chondrocytes were transduced with PRG4 (lubricin) promoter-driven Gaussia luciferase, allowing for temporal assessment of lubricin expression. A lubricin expression-driven Design of Experiment screen and subsequent validation identified 14% GelMA/2% OMA for further study. Therefore, DoE optimized 14% GelMA/2% OMA, 14% GelMA control, and 16% GelMA (total solid content control) were 3D bioprinted. The combination of lubricin protein expression and shape retention over the 22 days in culture, successfully determined the 14% GelMA/2%OMA to be the optimal formulation for lubricin secretion. This strategy allows for rapid analysis of the role(s) of biomaterial composition, stiffness or other cell manipulations on lubricin expression by chondrocytes, which may improve therapeutic strategies for cartilage regeneration. Full article
(This article belongs to the Special Issue Tissue Engineering Scaffolds in Regenerative Medicine)
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20 pages, 4846 KiB  
Article
Efficient Decellularization of the Full-Thickness Rat-Derived Abdominal Wall to Produce Acellular Biologic Scaffolds for Tissue Reconstruction: Promising Evidence Acquired from In Vitro Results
by George Skepastianos, Panagiotis Mallis, Epameinondas Kostopoulos, Efstathios Michalopoulos, Vasileios Skepastianos, Chrysoula Palazi, Lucia Pannuto and Gerasimos Tsourouflis
Bioengineering 2023, 10(8), 913; https://doi.org/10.3390/bioengineering10080913 - 1 Aug 2023
Cited by 1 | Viewed by 1260
Abstract
Background: Functional restoration of abdominal wall defects represents one of the fundamental challenges of reconstructive surgery. Synthetic grafts or crosslinked animal-derived biological grafts are characterized by significant adverse reactions, which are mostly observed after their implantation. The aim of this study was to [...] Read more.
Background: Functional restoration of abdominal wall defects represents one of the fundamental challenges of reconstructive surgery. Synthetic grafts or crosslinked animal-derived biological grafts are characterized by significant adverse reactions, which are mostly observed after their implantation. The aim of this study was to evaluate the efficacy of the decellularization protocol to produce a completely acellular full-thickness abdominal wall scaffold. Methods: Full-thickness abdominal wall samples were harvested from Wistar rats and submitted to a three-cycle decellularization process. Histological, biochemical, and DNA quantification analyses were applied to evaluate the effect of the decellularization protocol. Mechanical testing and immunogenicity assessment were also performed. Results: Histological, biochemical, and DNA analysis results showed efficient decellularization of the abdominal wall samples after the third cycle. Decellularized abdominal wall scaffolds were characterized by good biochemical and mechanical properties. Conclusion: The data presented herein confirm the effective production of a rat-derived full-thickness abdominal wall scaffold. Expanding this approach will allow the exploitation of the capacity of the proposed decellularization protocol in producing acellular abdominal wall scaffolds from larger animal models or human cadaveric donors. In this way, the utility of biological scaffolds with preserved in vivo remodeling properties may be one step closer to its application in clinical studies. Full article
(This article belongs to the Special Issue Tissue Engineering Scaffolds in Regenerative Medicine)
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11 pages, 1645 KiB  
Article
Selection of Mechanical Fragmentation Methods Based on Enzyme-Free Preparation of Decellularized Adipose-Derived Matrix
by Jiayi Feng, Su Fu and Jie Luan
Bioengineering 2023, 10(7), 758; https://doi.org/10.3390/bioengineering10070758 - 25 Jun 2023
Cited by 2 | Viewed by 1514
Abstract
Background: The decellularized adipose-derived matrix (DAM) has emerged as a promising biomaterial for inducing adipose tissue regeneration. Various methods have been employed to produce DAM, among which the enzyme-free method is a relatively recent preparation technique. The mechanical fragmentation step plays a crucial [...] Read more.
Background: The decellularized adipose-derived matrix (DAM) has emerged as a promising biomaterial for inducing adipose tissue regeneration. Various methods have been employed to produce DAM, among which the enzyme-free method is a relatively recent preparation technique. The mechanical fragmentation step plays a crucial role in determining the efficacy of the enzyme-free preparation. Methods: The adipose tissue underwent fragmentation through the application of ultrasonication, homogenization, and freeze ball milling. This study compared the central temperature of the mixture immediately following crushing, the quantity of oil obtained after centrifugation, and the thickness of the middle layer. Fluorescence staining was utilized to compare the residual cell activity of the broken fat in the middle layer, while electron microscopy was employed to assess the integrity and properties of the adipocytes among the three methods. The primary products obtained through the three methods were subsequently subjected to processing using the enzyme-free method DAM. The assessment of degreasing and denucleation of DAM was conducted through HE staining, oil red staining, and determination of DNA residues. Subsequently, the ultrasonication-DAM (U-DAM) and homogenation-DAM (H-DAM) were implanted bilaterally on the back of immunocompromised mice, and a comparative analysis of their adipogenic and angiogenic effects in vivo was performed. Results: Oil discharge following ultrasonication and homogenization was significantly higher compared to that observed after freeze ball milling (p < 0.001), despite the latter exhibiting the lowest center temperature (p < 0.001). The middle layer was found to be thinnest after ultrasonication (p < 0.001), and most of the remaining cells were observed to be dead following fragmentation. Except for DAM obtained through freeze ball milling, DAM obtained through ultrasonication and homogenization could be completely denucleated and degreased. In the in vivo experiment, the first adipocytes were observed in U-DAM as early as 1 week after implantation, but not in H-DAM. After 8 weeks, a significant number of adipocytes were regenerated in both groups, but the U-DAM group demonstrated a more efficient adipose regeneration than in H-DAM (p = 0.0057). Conclusions: Ultrasonication and homogenization are effective mechanical fragmentation methods for breaking down adipocytes at the initial stage, enabling the production of DAM through an enzyme-free method that facilitates successful regeneration of adipose tissues in vivo. Furthermore, the enzyme-free method, which is based on the ultrasonication pre-fragmentation approach, exhibits superior performance in terms of denucleation, degreasing, and the removal of non-adipocyte matrix components, thereby resulting in the highest in vivo adipogenic induction efficiency. Full article
(This article belongs to the Special Issue Tissue Engineering Scaffolds in Regenerative Medicine)
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