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Extracellular Matrix Biomaterial for Tissue Engineering and Regenerative Medicine, 2nd...
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Extracellular Matrix Biomaterial for Tissue Engineering and Regenerative Medicine, 2nd Edition

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

Deadline for manuscript submissions: 31 October 2026 | Viewed by 6846

Editors

Dr. Elizabeth C. Martin

E-Mail Website
Guest Editor
Section of Hematology and Medical Oncology, Department of Medicine, Tulane University School of Medicine, New Orleans, LA 70112, USA
Interests: extracellular matrix; tissue engineering; tumor microenvironment; stem cells; breast cancer
Special Issues, Collections and Topics in MDPI journals
Dr. Jorge Alfonso Belgodere

E-Mail Website
Guest Editor
Section of Hematology and Medical Oncology, Department of Medicine, Tulane University School of Medicine, New Orleans, LA 70112, USA
Interests: 3D bioprinting; photo-crosslinkable biomaterials; extracellular matrix; breast cancer; microphysiological systems; microfluidics
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The development of benchtop models and superior biomaterials that better recapitulate native conditions is of critical importance for more accurate disease modeling and tissue engineering applications. Key components of native tissue can include stromal cells, the extracellular matrix (ECM), and surrounding signaling molecules. Chief among the components is the ECM, composed of several classes of macromolecules that are each responsible for balancing the physical and chemical composition. The ECM’s topography (fiber diameter and orientation) plays a critical role in cell adhesion, migration, and proliferation, with changes leading to mechanical stimuli altering signaling pathways. Changes in protein composition and matrix stiffness have also been identified when tissue undergoes trauma or disease. The second edition of this Special Issue “Extracellular Matrix Biomaterial for Tissue Engineering and Regenerative Medicine” is focused on recent advancements in investigating the properties of the extracellular matrix and developing tools to recapitulate in vivo properties for use within tissue engineering and regenerative medicine applications.

The scope of this Special Issue includes, but is not limited to, the following topics:

  • Novel methods to generate, isolate, and characterize the ECM;
  • ECM protein distribution or changes;
  • Disease modeling using native ECMs;
  • Engineered biomaterials;
  • Three-dimensional biofabrication methods;
  • New technologies for synthetic materials to mimic native tissue.

Bringing together experts across different disciplines is paramount for the field to continue to develop and further increase its scientific impact.

Dr. Elizabeth C. Martin
Dr. Jorge Alfonso Belgodere
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 250 words) can be sent to the Editorial Office for assessment.

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-anonymized 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

  • extracellular matrix
  • ECM protein
  • biomaterials
  • 3D bioprinting
  • tissue engineering
  • regenerative medicine

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Related Special Issue

Published Papers (5 papers)

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Research

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24 pages, 5089 KB  
Article
A 3D Tissue-Engineering Model of Craniosynostosis to Study the Microenvironmental Signals Leading to Premature Suture Ossification
by Mariangela Meyer, Holmfridur Rist Jonsdottir, Isabel Amado, Javier Gutierrez Gonzalez, Shirley Bracken, Kulwinder Kaur, Tom Hodgkinson, Dylan J. Murray, Arlyng González-Vázquez and Fergal J. O’Brien
Bioengineering 2026, 13(7), 746; https://doi.org/10.3390/bioengineering13070746 - 26 Jun 2026
Viewed by 1572
Abstract
Craniosynostosis is a congenital bone developmental condition characterized by the premature ossification of calvarial sutures, leading to restricted skull expansion and potential neurological complications. Although little is known about the signaling that governs this accelerated fusion, our research group has previously identified a [...] Read more.
Craniosynostosis is a congenital bone developmental condition characterized by the premature ossification of calvarial sutures, leading to restricted skull expansion and potential neurological complications. Although little is known about the signaling that governs this accelerated fusion, our research group has previously identified a stiffness-dependent upregulation of osteogenic genes in cells derived from fused sutures, highlighting the role of mechanotransduction in disease progression. Building on these findings, the present study describes the development of a unique patient-derived three-dimensional (3D) tissue-engineering (TE) model of non-syndromic craniosynostosis (NS-CS) to investigate how extracellular matrix (ECM) composition and biochemical cues regulate ossification timing and patterns. Cells isolated from clinically relevant tissues, surgically obtained from patent and prematurely fused calvarial sutures of pediatric NS-CS patients, were characterized and cultured under both two-dimensional (2D) and 3D suture-mimicking conditions. Comparative analysis revealed differences in cellular responsiveness between cells isolated from fused and patent sutures across the different experimental conditions, with cells from fused sutures consistently exhibiting higher expression of osteogenic markers. Notably, the elevated expression of osteogenic and chondrogenic markers suggested the possible involvement of endochondral-like ossification mechanisms during the pathological process of suture fusion. This patient-derived model was designed to recapitulate biophysical and biochemical features of the extracellular matrix of healthy and pathological sutures, serving as a tool for future research, helping us to understand the underlying mechanisms behind the pathophysiology of craniosynostosis. Full article
(This article belongs to the Special Issue Extracellular Matrix Biomaterial for Tissue Engineering and Regenerative Medicine, 2nd Edition)
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17 pages, 3073 KB  
Article
Toward More Translational Tumor Models: Breast dECM-Based 3D Systems Capture Native Microenvironmental Cues
by Katherine L. Hebert, Jonathan J. Savoie, Mackenzie L. Hawes, Britney Nguyen, Madison Lee, Marcus A. Moody, Sophie R. Dietrich, Thomas Cheng, Van H. Barnes, Bridgette M. Collins-Burow, Alison A. Smith, Frank H. Lau, W. Todd Monroe, Matthew E. Burow, Elizabeth C. Martin and Jorge A. Belgodere
Bioengineering 2026, 13(6), 712; https://doi.org/10.3390/bioengineering13060712 - 21 Jun 2026
Viewed by 703
Abstract
Current 3D tumor models for aggressive breast cancers inadequately recapitulate the native tumor microenvironment (TME), leading to poor translational potential. There is a critical need for models capable of mimicking the unique biochemical signals present in the TME. To address this gap, breast [...] Read more.
Current 3D tumor models for aggressive breast cancers inadequately recapitulate the native tumor microenvironment (TME), leading to poor translational potential. There is a critical need for models capable of mimicking the unique biochemical signals present in the TME. To address this gap, breast tissue and a patient-derived xenograft tumor were decellularized and processed to produce breast tissue- and tumor-specific decellularized extracellular matrices (dECM). Histology confirmed complete cellular removal while maintaining the ECM. Further, DNA content was significantly reduced while ECM composition (POSTN, COLI, FN1) was retained. Breast dECM was incorporated (0, 5, 10, 20, and 50 µg/mL) with triple-negative breast cancer cell lines to generate spheroids. Imaging and histology demonstrated that cells in low dECM (5 and 10 µg/mL) formed compact singular spheres, while higher dECM concentrations (20 and 50 µg/mL) resulted in cells concentrated on the outer edge of the sphere and irregular sphere circularity. RNA-sequencing of MDA-MB-231 dECM spheres demonstrated that gene changes were mediated by both the inclusion of dECM and its composition. High-density tumor dECM upregulated genes associated with metastasis, while high-density breast dECM enhanced tumor suppressors and anti-metastasis genes. These findings indicate that dECM provides physiological cues in 3D tumor models by incorporating TME. Full article
(This article belongs to the Special Issue Extracellular Matrix Biomaterial for Tissue Engineering and Regenerative Medicine, 2nd Edition)
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19 pages, 2907 KB  
Article
Transcriptomic Analysis of Tendon Healing Using an Extracellular Matrix-Coated, Polyurethane Scaffold
by Ying Rao, Marianne Lauwers, Shuting Huang, Yuyue Zhang, Dai Fei Elmer Ker, Rocky S. Tuan and Dan Michelle Wang
Bioengineering 2026, 13(6), 652; https://doi.org/10.3390/bioengineering13060652 - 31 May 2026
Viewed by 698
Abstract
Large rotator cuff tendon injuries pose a dual clinical challenge: poor inherent healing capacity and high mechanical demands. To address this, we have developed a bifunctional scaffold that combines a slow-degrading, mechanically robust polyurethane core coated with tendon-derived extracellular matrix (ECM) extract to [...] Read more.
Large rotator cuff tendon injuries pose a dual clinical challenge: poor inherent healing capacity and high mechanical demands. To address this, we have developed a bifunctional scaffold that combines a slow-degrading, mechanically robust polyurethane core coated with tendon-derived extracellular matrix (ECM) extract to provide both structural support and regenerative cues. In a rabbit model of supraspinatus tendon injury, this ECM-polyurethane scaffold facilitated healing of critical-sized defects, resulting in aligned, tendon-like tissue with improved biomechanical properties. This study further explored the tendon healing mechanisms of the ECM-polyurethane scaffold in a rabbit model of large supraspinatus tendon injury using transcriptomic and qPCR analyses. At one month post-surgery, while both ECM-coated and uncoated polyurethane scaffolds initially provoked similar inflammatory responses when compared to healthy tendon, their healing pathways diverged significantly. The control polyurethane scaffold activated pathways associated with adipose tissue development, a non-functional outcome, whereas the ECM-coated scaffold actively directed healing toward tendon regeneration. These results demonstrate that the ECM coating is the critical factor driving divergent healing responses in polyurethane scaffolds, even though their underlying biomechanical properties are similar. This underscores the importance of combining biomechanical reinforcement with biologically active regenerative signals for effective regeneration of tendon and other load-bearing tissues. Full article
(This article belongs to the Special Issue Extracellular Matrix Biomaterial for Tissue Engineering and Regenerative Medicine, 2nd Edition)
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17 pages, 4590 KB  
Article
Beyond Decellularization: Remnant Mitochondrial DNA Can Act as Hidden Damage-Associated Molecular Pattern
by Elena V. A. van Hengel, Kuan Liu, Henk P. Roest, Jorke Willemse, Kimberley Ober-Vliegen, Selina M. W. Teurlings, Jeroen de Jonge, Monique M. A. Verstegen and Luc J. W. van der Laan
Bioengineering 2026, 13(2), 193; https://doi.org/10.3390/bioengineering13020193 - 9 Feb 2026
Cited by 1 | Viewed by 1440
Abstract
Tissue decellularization aims to obtain bioscaffolds for regenerative applications by removing all cellular components while preserving the extracellular matrix (ECM) architecture. Although decellularization removes the majority of linear nuclear DNA (nDNA), residual amounts remain detectable. However, the fate of circular mitochondrial DNA (mtDNA) [...] Read more.
Tissue decellularization aims to obtain bioscaffolds for regenerative applications by removing all cellular components while preserving the extracellular matrix (ECM) architecture. Although decellularization removes the majority of linear nuclear DNA (nDNA), residual amounts remain detectable. However, the fate of circular mitochondrial DNA (mtDNA) after decellularization has not yet been reported. Cell death or injury can cause the release of mtDNA, which is resistant to breakdown by exonucleases. Extracellular mtDNA acts as a damage-associated molecular pattern (DAMP) that can trigger immune responses. The aim of this study is to assess the presence of residual mtDNA in the liver, bile duct, and vascular scaffolds after decellularization and whether this causes inflammatory responses in macrophages. Decellularized tissues showed a marked reduction in total DNA content well below the threshold of 50 ng/mg tissue. However, in liver and vascular scaffolds, a relative increase in the mtDNA:nDNA ratio was detected in the remnant DNA fraction. Residual mtDNA in bioscaffolds acted as DAMPs causing macrophage activation, as shown by increased cell proliferation and cytokine production. Strategies to further reduce remnant mtDNA were tested. We found that treatment with the endonuclease enzyme HpaII was effective in degrading residual mtDNA. Importantly, mtDNA removal resulted in a significantly reduced macrophage activation. In conclusion, our study shows that mtDNA is relatively resistant to the decellularization procedure and can act as a DAMP in bioscaffolds. This underscores the importance of removing mtDNA from decellularized bioscaffolds to improve the immunocompatibility for biomedical applications. Full article
(This article belongs to the Special Issue Extracellular Matrix Biomaterial for Tissue Engineering and Regenerative Medicine, 2nd Edition)
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17 pages, 1285 KB  
Review
The Extracellular Matrix in Liver Regeneration: Biological and Therapeutic Insights
by Haodong Ma, Wenyue Wu, Wen Zhang, Hong Li, Ziyan Pan, Caihong Wang, Ruoyu Gao, Qiushuang Ji, Zhi Chen, Hong You and Wei Chen
Bioengineering 2026, 13(3), 335; https://doi.org/10.3390/bioengineering13030335 - 13 Mar 2026
Cited by 1 | Viewed by 1707
Abstract
The liver possesses a remarkable regenerative capacity following injury, a process fundamentally orchestrated by the dynamic extracellular matrix (ECM). Far beyond a passive scaffold, the liver matrisome functions as an integrative mechano-biochemical circuit. It comprises a core structural network together with regulatory non-core [...] Read more.
The liver possesses a remarkable regenerative capacity following injury, a process fundamentally orchestrated by the dynamic extracellular matrix (ECM). Far beyond a passive scaffold, the liver matrisome functions as an integrative mechano-biochemical circuit. It comprises a core structural network together with regulatory non-core components that collectively establish a dynamic niche. This niche stores and releases mitogenic cues, transmits mechanical forces, and coordinates multicellular crosstalk. Through receptors like integrins and mechanosensitive channels, ECM-derived signals converge on key pathways, including Hippo-YAP/TAZ and Wnt/β-catenin, to drive hepatocyte proliferation and tissue restructuring. The balance between matrix stabilization and remodeling dictates the outcome, guiding physiological regeneration versus fibrotic progression. Consequently, the ECM emerges as a central therapeutic target and a blueprint for engineering strategies aimed at restoring liver function. Strategies to recalibrate its composition, mechanics, and remodeling, from pharmacological inhibitors to bioengineered decellularized ECM scaffolds, hold significant potential for steering liver repair and combating chronic liver disease. Full article
(This article belongs to the Special Issue Extracellular Matrix Biomaterial for Tissue Engineering and Regenerative Medicine, 2nd Edition)
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