Engineering injectable, biocompatible, and highly elastic bioadhesive cryogels

Devyesh Rana; Thibault Colombani; Bahram Saleh; Halimatu S Mohammed; Nasim Annabi; Sidi A Bencherif

doi:10.1016/j.mtbio.2023.100572

Engineering injectable, biocompatible, and highly elastic bioadhesive cryogels

Mater Today Bio. 2023 Feb 1:19:100572. doi: 10.1016/j.mtbio.2023.100572. eCollection 2023 Apr.

Authors

Devyesh Rana¹, Thibault Colombani¹, Bahram Saleh¹, Halimatu S Mohammed¹, Nasim Annabi^{2

3}, Sidi A Bencherif^{1

4

5

6}

Affiliations

¹ Department of Chemical Engineering, Northeastern University, Boston, MA, USA.
² Department of Chemical and Biomolecular Engineering, University of California, Los Angeles, Los Angeles, CA, USA.
³ Department of Bioengineering, University of California, Los Angeles, Los Angeles, CA, USA.
⁴ Department of Bioengineering, Northeastern University, Boston, MA, USA.
⁵ Harvard John A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, USA.
⁶ Sorbonne University, UTC CNRS UMR 7338, Biomechanics and Bioengineering (BMBI), University of Technology of Compiègne, Compiègne, France.

Abstract

The extracellular matrix (ECM), an integral component of all organs, is inherently tissue adhesive and plays a pivotal role in tissue regeneration and remodeling. However, man-made three-dimensional (3D) biomaterials that are designed to mimic ECMs do not intrinsically adhere to moisture-rich environments and often lack an open macroporous architecture required for facilitating cellularization and integration with the host tissue post-implantation. Furthermore, most of these constructs usually entail invasive surgeries and potentially a risk of infection. To address these challenges, we recently engineered biomimetic and macroporous cryogel scaffolds that are syringe injectable while exhibiting unique physical properties, including strong bioadhesive properties to tissues and organs. These biomimetic catechol-containing cryogels were prepared from naturally-derived polymers such as gelatin and hyaluronic acid and were functionalized with mussel-inspired dopamine (DOPA) to impart bioadhesive properties. We found that using glutathione as an antioxidant and incorporating DOPA into cryogels via a PEG spacer arm led to the highest tissue adhesion and improved physical properties overall, whereas DOPA-free cryogels were weakly tissue adhesive. As shown by qualitative and quantitative adhesion tests, DOPA-containing cryogels were able to adhere strongly to several animal tissues and organs such as the heart, small intestine, lung, kidney, and skin. Furthermore, these unoxidized (i.e., browning-free) and bioadhesive cryogels showed negligible cytotoxicity toward murine fibroblasts and prevented the ex vivo activation of primary bone marrow-derived dendritic cells. Finally, in vivo data suggested good tissue integration and a minimal host inflammatory response when subcutaneously injected in rats. Collectively, these minimally invasive, browning-free, and strongly bioadhesive mussel-inspired cryogels show great promise for various biomedical applications, potentially in wound healing, tissue engineering, and regenerative medicine.

Keywords: Bioadhesion; Biopolymers; Cryogel; Dopamine; Tissue adhesive.

Grants and funding

R01 EB027705/EB/NIBIB NIH HHS/United States