Decellularized bone matrix/oleoyl chitosan derived supramolecular injectable hydrogel promotes efficient bone integration

Sayanti Datta; Arun Prabhu Rameshbabu; Kamakshi Bankoti; Madhurima Roy; Chandrika Gupta; Subhodeep Jana; Amit Kumar Das; Ramkrishna Sen; Santanu Dhara

doi:10.1016/j.msec.2020.111604

Decellularized bone matrix/oleoyl chitosan derived supramolecular injectable hydrogel promotes efficient bone integration

Mater Sci Eng C Mater Biol Appl. 2021 Feb:119:111604. doi: 10.1016/j.msec.2020.111604. Epub 2020 Oct 9.

Authors

Sayanti Datta¹, Arun Prabhu Rameshbabu¹, Kamakshi Bankoti¹, Madhurima Roy², Chandrika Gupta², Subhodeep Jana¹, Amit Kumar Das², Ramkrishna Sen², Santanu Dhara³

Affiliations

¹ Biomaterials and Tissue Engineering Laboratory, School of Medical Science and Technology, Indian Institute of Technology Kharagpur, Kharagpur 721302, India.
² Department of Biotechnology, Indian Institute of Technology Kharagpur, Kharagpur 721302, India.
³ Biomaterials and Tissue Engineering Laboratory, School of Medical Science and Technology, Indian Institute of Technology Kharagpur, Kharagpur 721302, India. Electronic address: sdhara@smst.iitkgp.ac.in.

PMID: 33321648
DOI: 10.1016/j.msec.2020.111604

Abstract

Hydrogels derived from decellularized extracellular matrix (ECM) have been widely used as a bioactive matrix for facilitating functional bone tissue regeneration. However, its poor mechanical strength and fast degradation restricts the extensive use for clinical application. Herein, we present a crosslinked decellularized bone ECM (DBM) and fatty acid modified chitosan (oleoyl chitosan, OC) based biohybrid hydrogel (DBM/OC) for delivering human amnion-derived stem cells (HAMSCs) for bone regeneration. DBM/OC hydrogel were benchmarked against collagen-I/OC (Col-I/OC) based hydrogel in terms of their morphological characteristics, rheological analysis, and biological performances. DBM/OC hydrogel with its endogenous growth factors recapitulates the nanofibrillar 3D tissue microenvironment with improved mechanical strength and also exhibited antimicrobial potential along with superior proliferation/differentiation ability. HAMSCs encapsulation potential of DBM/OC hydrogel was established by well spread cytoskeleton morphology post 14 days of cultivation. Further, ex-vivo chick chorioallantoic membrane (CAM) assay revealed excellent neovascularization potential of DBM/OC hydrogel. Subcutaneously implanted DBM/OC hydrogel did not trigger any severe immune response or infection in the host after 21 days. Also, DBM/OC hydrogels and HAMSCs encapsulated DBM/OC hydrogels were implanted at the tibial defect in a rabbit model to assess the bone regeneration ability. Quantitative micro-CT and histomorphological analysis demonstrated that HAMSCs encapsulated DBM/OC hydrogel can support more mature mineralized bone formation at the defect area compared to DBM/OC hydrogel or SHAM. These findings manifested the efficacy of DBM/OC hydrogel as a functional cell-delivery vehicle and osteoinductive template to accelerate bone regeneration.

Keywords: Bone regeneration; Decellularized bone matrix; Nanofibrillar hybrid hydrogel; Neovascularization; Oleoyl chitosan; Stem cell encapsulation.

MeSH terms

Animals
Bone Matrix
Bone Regeneration
Chitosan*
Extracellular Matrix
Hydrogels* / pharmacology
Rabbits

Substances

Hydrogels
Chitosan