Combinatorial Screening of Nanoclay-Reinforced Hydrogels: A Glimpse of the "Holy Grail" in Orthopedic Stem Cell Therapy?

Masoud Hasany, Ashish Thakur, Nayere Taebnia, Firoz Babu Kadumudi, Mohammad-Ali Shahbazi, Malgorzata Karolina Pierchala, Soumyaranjan Mohanty, Gorka Orive, Thomas Lars Andresen, Casper Bindzus Foldager, Soheila Yaghmaei, Ayyoob Arpanaei, Akhilesh K. Gaharwar, Mehdi Mehrali, Alireza Dolatshahi-Pirouz*

*Corresponding author for this work

    Research output: Contribution to journalJournal articleResearchpeer-review


    Despite the promise of hydrogel-based stem cell therapies in orthopedics, a significant need still exists for the development of injectable microenvironments capable of utilizing the regenerative potential of donor cells. Indeed, the quest for biomaterials that can direct stem cells into bone without the need of external factors has been the "Holy Grail" in orthopedic stem cell therapy for decades. To address this challenge, we have utilized a combinatorial approach to screen over 63 nanoengineered hydrogels made from alginate, yaluronic acid and two-dimensional nanocla, ys. Out of these combinations, we have identified a biomaterial that these combinations, we have identified a biomaterial that can promote osteogenesis in the absence of well-established differentiation factors such as bone morphogenetic protein 2 (BMP2) or dexamethasone. Notably, in our "hit" formulations we observed a 36-fold increase in alkaline phosphate (ALP) activity and a 11-fold increase in the formation of mineralized matrix, compared to the control hydrogel. This induced osteogenesis was further supported by X-ray diffraction, scanning electron microscopy, Fourier transform infrared spectroscopy, and energy-dispersive X-ray spectroscopy. Additionally, the Montmorillonite-reinforced hydrogels exhibited high osteointegration as evident from the relatively stronger adhesion to the bone explants as compared to the control. Overall, our results demonstrate the capability of combinatorial and nanoengineered biomaterials to induce bone regeneration through osteoinduction of stem cells in a natural and differentiation-factor-free environment.
    Original languageEnglish
    JournalACS Applied Materials and Interfaces
    Issue number41
    Pages (from-to)34924-34941
    Publication statusPublished - 2018


    • Nanomaterials
    • Nanocomposite hydrogels
    • Nanoclays
    • Cyborganics
    • Tissue engineering
    • Osteoinduction
    • Human mesenchymal stem cells
    • Bone


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