Cyclodextrin in tissue engineering

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The field of tissue engineering continues to advance, sometimes in exponential leaps forward, but also sometimes at a rate that does not fulfill the promise that the field imagined a few decades ago. This review is in part a catalog of success in an effort to inform the process of innovation. Tissue engineering has recruited new technologies and developed new methods for engineering tissue constructs that can be used to mitigate or model disease states for study. Key to this antecedent statement is that the scientific effort must be anchored in the needs of a disease state and be working toward a functional product in regenerative medicine. It is this focus on the wildly important ideas coupled with partnered research efforts within both academia and industry that have shown most translational potential. The field continues to thrive and among the most important recent developments are the use of three-dimensional bioprinting, organ-on-a-chip, and induced pluripotent stem cell technologies that warrant special attention. [1]

Hydrogels have been extensively used for 3D bioprinting, which has been a very active area of research in the past few years. Hydrogels can be made from various natural or synthetic polymers and have been used for the engineering of different tissues, because of their ability to encapsulate cells, while having the permeability required for the diffusion of O2 and nutrients across the material. An aspect in which previously they have fallen short is their mechanical properties and the lack of adhesiveness. Recently, however, these problems were largely addressed. [1]

Cyclodextrins with good biocompatibility and biodegradability profile have been studied by several groups aiming at bone regeneration, cartilage tissue engineering [2-6]. For instance, a freeze-dried 3D scaffold-based on cellulose nanofiber-cyclodextrin loaded with raloxifene hydrochloride (an osteoporosis drug) succeeded in promoting cell adhesion, ALP expression, and calcium ion deposition by providing a long-term release within 20 days [2]. Chitosan/β-cyclodextrin nanogels loaded with adenosine have been investigated for the coating of the inner luminal surface of tissue-engineered blood vessels [3].

[1] Nureddin Ashammakhi, Amin GhavamiNejad, Rumeysa Tutar, Annabelle Fricker, Ipsita Roy, Xanthippi Chatzistavrou, Ehsanul Hoque Apu, Kim-Lien Nguyen, Taby Ahsan, Ippokratis Pountos, and Edward J. Caterson: Highlights on Advancing Frontiers in Tissue Engineering. Tissue Engineering Part B: Reviews 2022, 633-664.

[2] M. A. Grimaudo, A. Concheiro, C. Alvarez-Lorenzo, Nanogels for regenerative medicine. Journal of Controlled Release, 2019, 313, 148-160,

[3] W. Chen, W. Zeng, Y.X. Wu, C. Wen, L. Li, G. Liu, L. Shen, M.C. Yang, J. Tan, C.H. Zhu, The construction of tissue-engineered blood vessels crosslinked with adenosine-loaded chitosan/beta-cyclodextrin nanoparticles using a layer-by-layer assembly method. Adv. Healthcare Mater., 2014, 3, 1776-1781.

[4] Kamel, R.; El-Wakil, N.A.; Abdelkhalek, A.A.; Elkasabgy, N.A. Nanofibrillated cellulose/cyclodextrin based 3D scaffolds loaded with raloxifene hydrochloride for bone regeneration. Int. J. Biol. Macromol. 2020156, 704–716.

[5] Chen, Y.; Li, N.; Yang, Y.; Liu, Y. A Dual targeting cyclodextrin/gold nanoparticle conjugate as a scaffold for solubilization and delivery of paclitaxel. RSC Adv. 20155, 8938–8941.

[6] J.H. Choi, A. Park, W. Lee, J. Youn, M.A. Rim, W. Kim, N. Kim, J.E. Song, G. Khang Preparation and characterization of an injectable dexamethasone-cyclodextrin complexes-loaded gellan gum hydrogel for cartilage tissue engineering. J. Control. Release, 2020, 327, 747-765

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