Advancements in Extracellular Matrix-Based Biomaterials and Biofabrication of 3D Organotypic Skin Models

Phang, Shou Jin; Basak, Soumyadeep; Teh, Huey Xhin; Gopinath, P.; Kuppusamy, Umah Rani; Neo, Yun Ping; Looi, Mee Lee

doi:10.1021/acsbiomaterials.2c00342

Cited by 18 publications

(11 citation statements)

References 177 publications

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“…ECM provides mechanical support and biochemical signals to cells. Advances and future possibilities in modifying ECM-based biomaterials to recreate disease-like skin models are highlighted given the importance of organotypic skin models in disease modeling [20].…”

Section: Vol 4 Iss 2 Year 2023 Mednext Journal Of Medical and Health ...mentioning

confidence: 99%

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3D bioprinting strategies and their application in studies in vivo and in vitro animal models for skin regeneration: a concise systematic review and meta-analysis

Mauro

Zotarelli-Filho

2023

MedNEXT

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Introduction: Annually, 50% of medical expenses worldwide stem from damage to the body's tissues and organs. Large skin defects can be caused by tumor excision, venous ulcers, diabetic foot ulcers, and burns. The 3D bioprinting of skin has an advantage compared to other technologies for skin substitutes, the capacity for directional and spatial handling at the cellular level with variable density. Objective: It was to identify the most efficient 3D bioprinting strategies and their application in studies in vivo and in vitro animal models, to demonstrate state of art in skin regeneration, and to direct new clinical research with translational studies. Methods: The rules of the Systematic Review-PRISMA Platform were followed. The research was carried out from November 2022 to February 2023 and developed based on Scopus, PubMed, Science Direct, Scielo, and Google Scholar. The quality of the studies was based on the GRADE instrument and the risk of bias was analyzed according to the Cochrane instrument. Results: A total of 237 articles were found and 97 articles were evaluated in full, and 16 were included and described in the present study. According to the GRADE instrument, most studies (X2 =90.5%>50%) followed a controlled clinical study model and had a good methodological design. the biases did not compromise the scientific basis of the studies. Conclusion: Most organotypic skin models have an epidermal layer of keratinocytes and a dermal layer of fibroblasts embedded in an extracellular matrix-based biomaterial. Furthermore, skin comprising epidermis, dermis, and hypodermis stratified with blood vessels, nerves, muscles, and cutaneous appendages can be fabricated. These findings provided evidence for further advances in translational studies in humans.

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Section: Vol 4 Iss 2 Year 2023 Mednext Journal Of Medical and Health ...mentioning

confidence: 99%

“…Added to this, the scientific articles developed about 3D bioprinting as a skin substitute, have gaps in its implementation in humans, highlighting that further research is needed to ensure the safety and feasibility of using this technology in humans [17][18][19][20].…”

Section: Introductionmentioning

confidence: 99%

3D bioprinting strategies and their application in studies in vivo and in vitro animal models for skin regeneration: a concise systematic review and meta-analysis

Mauro

Zotarelli-Filho

2023

MedNEXT

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“…Another feature of these platforms is their composition; in healthy tissue, ECM plays a vital role in supporting cell growth and behavior by providing structural, mechanical, and bioactive cues . In recent years, single and multiple ECM proteins have been incorporated into polymer scaffolds to improve their biocompatibility and function. − However, a single protein cannot mimic all functions attributed to whole ECM. , Whole-organ decellularized ECM incorporated into artificial scaffolds has shown advantages such as affecting hydrophilicity, cell adhesion, proliferation, and behavior. ,− This has also been seen with hepatocytes, with studies showing that rat and human liver dECM can impact cell survival and proliferation. ,,, …”

Section: Introductionmentioning

confidence: 99%

A Unification of Nanotopography and Extracellular Matrix in Electrospun Scaffolds for Bioengineered Hepatic Models

Gao

Bate

Callanan

2023

ACS Appl. Bio Mater.

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Donor liver shortage is a crucial global public health problem as whole-organ transplantation is the only definitive cure for liver disease. Liver tissue engineering aims to reproduce or restore function through in vitro tissue constructs, which may lead to alternative treatments for active and chronic liver disease. The formulation of a multifunctional scaffold that has the potential to mimic the complex extracellular matrix (ECM) and their influence on cellular behavior, are essential for culturing cells on a construct. The separate employment of topographic or biological cues on a scaffold has both shown influences on hepatocyte survival and growth. In this study, we investigate both of these synergistic effects and developed a new procedure to directly blend whole-organ vascular perfusion-decellularized rat liver ECM (dECM) into electrospun fibers with tailored surface nanotopography. Water contact angle, tensile test, and degradation studies were conducted to analyze scaffold hydrophilicity, mechanical properties, and stability. The results show that our novel hybrid scaffolds have enhanced hydrophilicity, and the nanotopography retained its original form after hydrolytic degradation for 14 days. Human hepatocytes (HepG2) were seeded to analyze the scaffold biocompatibility. Cell viability and DNA quantification imply steady cell proliferation over the culture period, with the highest albumin secretion observed on the hybrid scaffold. Scanning electron microscopy shows that cell morphology was distinctly different on hybrid scaffolds compared to control groups, where HepG2 began to form a monolayer toward the end of the culture period; meanwhile, typical hepatic markers and ECM genes were also influenced, such as an increasing trend of albumin appearing on the hybrid scaffolds. Taken together, our findings provide a reproducible approach and utilization of animal tissue-derived ECM and emphasize the synergism of topographical stimuli and biochemical cues on electrospun scaffolds in liver tissue engineering.

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“…The obstacles between research and clinical application are the time-consuming preparation and limited human dECM resources. 24,25 An ideal solution would be to create an affordable skin substitute that can be fabricated from autologous materials and has the functional and structural properties of normal human skin.…”

Section: Introductionmentioning

confidence: 99%

3D-Bioprinted Biomimetic Multilayer Implants Comprising Microfragmented Adipose Extracellular Matrix and Cells Improve Wound Healing in a Murine Model of Full-Thickness Skin Defects

Zhang

Lai

et al. 2023

ACS Appl. Mater. Interfaces

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Repairing full-thickness skin defects is a major challenge in clinical practice. Three-dimensional (3D) bioprinting of living cells and biomaterials is a promising technique to resolve this challenge. However, the time-consuming preparation and limited sources of biomaterials are bottlenecks that must be addressed. Therefore, we developed a simple and fast method to directly process adipose tissue into a microfragmented adipose extracellular matrix (mFAECM) as the main component of bioink to fabricate 3D-bioprinted, biomimetic, multilayer implants. The mFAECM retained most of the collagen and sulfated glycosaminoglycans in the native tissue. In vitro, the mFAECM composite demonstrated biocompatibility, printability, and fidelity and could support cell adhesion. In a full-thickness skin defect model in nude mice, cells encapsulated in the implant survived and participated in wound repair after implantation. The basic structures of the implant were maintained throughout wound healing and gradually metabolized. The biomimetic multilayer implants fabricated via mFAECM composite bioinks and cells could accelerate wound healing by promoting the contraction of new tissue inside the wound, collagen secretion and remodeling, and neovascularization. This study provides an approach for improving the timeliness of fabricating 3D-bioprinted skin substitutes and may offer a useful tool for treating full-thickness skin defects.

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Advancements in Extracellular Matrix-Based Biomaterials and Biofabrication of 3D Organotypic Skin Models

Cited by 18 publications

References 177 publications

3D bioprinting strategies and their application in studies in vivo and in vitro animal models for skin regeneration: a concise systematic review and meta-analysis

3D bioprinting strategies and their application in studies in vivo and in vitro animal models for skin regeneration: a concise systematic review and meta-analysis

A Unification of Nanotopography and Extracellular Matrix in Electrospun Scaffolds for Bioengineered Hepatic Models

3D-Bioprinted Biomimetic Multilayer Implants Comprising Microfragmented Adipose Extracellular Matrix and Cells Improve Wound Healing in a Murine Model of Full-Thickness Skin Defects

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