Thavasyappan Thambi (경희대학교)

한빛사논문

조회400

경희대학교

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J. Nanobiotechnol., Nov 02 2023, 21 (1) 405 | https://doi.org/10.1186/s12951-023-02160-2 Nanoengineered injectable hydrogels derived from layered double hydroxides and alginate for sustained release of protein therapeutics in tissue engineering applications

V. H. Giang Phan¹, Hai‑Sang Duong¹, Quynh‑Giao Thi Le¹, Gopinathan Janarthanan², Sanjairaj Vijayavenkataraman^2,3, Hoang‑Nam Huynh Nguyen¹, Bich‑Phuong Thi Nguyen¹, Panchanathan Manivasagan⁴, Eue‑Soon Jang⁴, Yi Li^5* and Thavasyappan Thambi^6*

¹Biomaterials and Nanotechnology Research Group, Faculty of Applied Sciences, Ton Duc Thang University, Ho Chi Minh City, Vietnam.

²The Vijay Lab, Division of Engineering, New York University Abu Dhabi, Abu Dhabi, United Arab Emirates.

³Department of Mechanical & Aerospace Engineering, Tandon School of Engineering, New York University, Brooklyn, NY 11201, USA.

⁴Department of Applied Chemistry, Kumoh National Institute of Technology, Daehak‑ro 61, Gumi, Gyeongbuk 39177, Republic of Korea.

⁵College of Materials and Textile Engineering & Nanotechnology Research Institute, Jiaxing University, Jiaxing 314001, Zhejiang, People’s Republic of China.

⁶Graduate School of Biotechnology, College of Life Sciences, Kyung Hee University, Yongin si, Gyeonggi do 17104, Republic of Korea.

*Correspondence: Yi Li, Thavasyappan Thambi

Abstract

Chronic Kidney Disease (CKD) which involves gradual loss of kidney function is characterized by low levels of a glycoprotein called Erythropoietin (EPO) that leads to red blood cell deficiency and anemia. Recombinant human EPO (rhEPO) injections that are administered intravenously or subcutaneously is the current gold standard for treating CKD. The rhEPO injections have very short half-lives and thus demands frequent administration with a risk of high endogenous EPO levels leading to severe side effects that could prove fatal. To this effect, this work provides a novel approach of using lamellar inorganic solids with a brucite-like structure for controlling the release of protein therapeutics such as rhEPO in injectable hydrogels. The nanoengineered injectable system was formulated by incorporating two-dimensional layered double hydroxide (LDH) clay materials with a high surface area into alginate hydrogels for sustained delivery. The inclusion of LDH in the hydrogel network not only improved the mechanical properties of the hydrogels (5-30 times that of alginate hydrogel) but also exhibited a high binding affinity to proteins without altering their bioactivity and conformation. Furthermore, the nanoengineered injectable hydrogels (INHs) demonstrated quick gelation, injectability, and excellent adhesion properties on human skin. The in vitro release test of EPO from conventional alginate hydrogels (Alg-Gel) showed 86% EPO release within 108 h while INHs showed greater control over the initial burst and released only 24% of EPO in the same incubation time. INH-based ink was successfully used for 3D printing, resulting in scaffolds with good shape fidelity and stability in cell culture media. Controlled release of EPO from INHs facilitated superior angiogenic potential in ovo (chick chorioallantoic membrane) compared to Alg-Gel. When subcutaneously implanted in albino mice, the INHs formed a stable gel in vivo without inducing any adverse effects. The results suggest that the proposed INHs in this study can be utilized as a minimally invasive injectable platform or as 3D printed patches for the delivery of protein therapeutics to facilitate tissue regeneration.

논문정보

형식Research article
게재일2023년 11월 (BRIC 등록일 2023-11-16)
연구진국내(교신)+국외 연구진
분야 바이오·의료융합 > 바이오소재

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