Biofabrication of Prevascularised Hypertrophic Cartilage Microtissues for Bone Tissue Engineering

Overview

Journal Front Bioeng Biotechnol

Date 2021 Jun 25

PMID 34169064

Citations 11

Authors

Jessica Nulty

Ross Burdis

Daniel J Kelly

Affiliations

Soon will be listed here.

Abstract

Bone tissue engineering (TE) has the potential to transform the treatment of challenging musculoskeletal pathologies. To date, clinical translation of many traditional TE strategies has been impaired by poor vascularisation of the implant. Addressing such challenges has motivated research into developmentally inspired TE strategies, whereby implants mimicking earlier stages of a tissue's development are engineered and then implanted to fully mature into the adult tissue. The goal of this study was to engineer tissues mimicking the immediate developmental precursor to long bones, specifically a vascularised hypertrophic cartilage template, and to then assess the capacity of such a construct to support endochondral bone formation . To this end, we first developed a method for the generation of large numbers of hypertrophic cartilage microtissues using a microwell system, and encapsulated these microtissues into a fibrin-based hydrogel capable of supporting vasculogenesis by human umbilical vein endothelial cells (HUVECs). The microwells supported the formation of bone marrow derived stem/stromal cell (BMSC) aggregates and their differentiation toward a hypertrophic cartilage phenotype over 5 weeks of cultivation, as evident by the development of a matrix rich in sulphated glycosaminoglycan (sGAG), collagen types I, II, and X, and calcium. Prevascularisation of these microtissues, undertaken 1 week prior to implantation, enhanced their capacity to mineralise, with significantly higher levels of mineralised tissue observed within such implants after 4 weeks within an ectopic murine model for bone formation. It is also possible to integrate such microtissues into 3D bioprinting systems, thereby enabling the bioprinting of scaled-up, patient-specific prevascularised implants. Taken together, these results demonstrate the development of an effective strategy for prevascularising a tissue engineered construct comprised of multiple individual microtissue "building blocks," which could potentially be used in the treatment of challenging bone defects.

Citing Articles

Rapidly Degrading Hydrogels to Support Biofabrication and 3D Bioprinting Using Cartilage Microtissues.

Kronemberger G, Spagnuolo F, Karam A, Chattahy K, Storey K, Kelly D ACS Biomater Sci Eng. 2024; 10(10):6441-6450.

PMID: 39240109 PMC: 11480940. DOI: 10.1021/acsbiomaterials.4c00819.

Three-Dimensional Bioprinting: A Comprehensive Review for Applications in Tissue Engineering and Regenerative Medicine.

Mirsky N, Ehlen Q, Greenfield J, Antonietti M, Slavin B, Nayak V Bioengineering (Basel). 2024; 11(8).

PMID: 39199735 PMC: 11351251. DOI: 10.3390/bioengineering11080777.

Exploring calcium-free alternatives in endochondral bone repair tested on trials - A review.

Cardenas-Aguazaco W, Lara-Bertrand A, Prieto-Abello L, Barreto-Lopez N, Camacho B, Silva-Cote I Regen Ther. 2024; 26:145-160.

PMID: 38872977 PMC: 11169084. DOI: 10.1016/j.reth.2024.05.017.

3D printed osteochondral scaffolds: design strategies, present applications and future perspectives.

Liu G, Wei X, Zhai Y, Zhang J, Li J, Zhao Z Front Bioeng Biotechnol. 2024; 12:1339916.

PMID: 38425994 PMC: 10902174. DOI: 10.3389/fbioe.2024.1339916.

Human Induced Pluripotent Spheroids' Growth Is Driven by Viscoelastic Properties and Macrostructure of 3D Hydrogel Environment.

Lemarie L, Dargar T, Grosjean I, Gache V, Courtial E, Sohier J Bioengineering (Basel). 2023; 10(12).

PMID: 38136009 PMC: 10740696. DOI: 10.3390/bioengineering10121418.

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