Journal
ACS APPLIED MATERIALS & INTERFACES
Volume 10, Issue 41, Pages 34924-34941Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acsami.8b11436
Keywords
nanomaterials; nanocomposite hydrogels; nanoclays; cyborganics; tissue engineering; osteoinduction; human mesenchymal stem cells; bone
Funding
- Danish Council for Independent Research (Technology and Production Sciences) [5054-00142B]
- Gigtforeningen [R139-A3864]
- Villum Foundation [10103]
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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.
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