Evaluation of the effect of co-transplantation of collagen-hydroxyapatite bio-scaffold containing nanolycopene and human endometrial mesenchymal stem cell derived exosomes to regenerate bone in rat critical size calvarial defect.

This study aimed to evaluate the effect of nanoparticles based on the PLGA and biomolecule of lycopene (i.e. NLcp) and exosomes loaded on hydroxyapatite/collagen-based scaffolds (HA/Coll), on human endometrial MSCs (hEnMSCs) differentiation into osteoblast cells. To this end, after synthesizing NLcp and isolating hEnMSC-derived exosomes, and studying their characterizations, HA/Coll scaffold with/without NLcp and exosome was fabricated. In following, the rat skull-defect model was created on 54 male Sprague-Dawley rats (12 weeks old) which were classified into 6 groups [control group (4 healthy rats), negative control group: bone defect without grafting (10 rats), and experimental groups including bone defect grafted with HA/Coll scaffold (10 rats), HA/Coll/NLcp scaffold (10 rats), HA/Coll scaffold + exosome (10 rats), and HA/Coll-NLcp scaffold + exosome (10 rats)]. Finally, the grafted membrane along with its surrounding tissues was removed at 90 days after surgery, to assess the amount of defect repair by Hematoxylin and eosin staining. Moreover, immunohistochemical and X-ray Micro-Computed Tomography (Micro-CT) analyses were performed to assess osteocalcin and mean bone volume fraction (BVF). Based on the results, although, the existence of the exosome in the scaffold network can significantly increase mean BVF compared to HA/Coll scaffold and HA/Coll-NLcp scaffold (2.25-fold and 1.5-fold, respectively). However, the combination of NLcp and exosome indicated more effect on mean BVF; so that the HA/Coll-NLcp scaffold + exosome led to a 15.95 % increase in mean BVF than the HA/Coll scaffold + exosome. Hence, synthesized NLcp in this study can act as a suitable bioactive to stimulate the osteogenic, promotion of cell proliferation and its differentiation when used in the polymer scaffold structure or loaded into polymeric carriers containing the exosome.

Quince seed mucilage-based scaffold as a smart biological substrate to mimic mechanobiological behavior of skin and promote fibroblasts proliferation and h-ASCs differentiation into keratinocytes.

The use of biological macromolecules like quince seed mucilage (QSM), as the common curative practice has a long history in traditional folk medicine to cure wounds and burns. However, this gel cannot be applied on exudative wounds because of the high water content and non-absorption of infection of open wounds. It also limits cell-to-cell interactions and leads to the slow wound healing process. In this study to overcome these problems, a novel QSM-based hybrid scaffold modified by PCL/PEG copolymer was designed and characterized. The properties of this scaffold (PCL/QSM/PEG) were also compared with four scaffolds of PCL/PEG, PCL/Chitosan/PEG, chitosan, and QSM, to assess the role of QSM and the combined effect of polymers in improving the function of skin tissue-engineered scaffolds. It was found, the physicochemical properties play a crucial role in regulating cell behaviors so that, PCL/QSM/PEG as a smart/stimuli-responsive bio-matrix promotes not only human-adipose stem cells (h-ASCs) adhesion but also supports fibroblasts growth, via providing a porous-network. PCL/QSM/PEG could also induce keratinocytes at a desirable level for wound healing, by increasing the mechanobiological signals. Immunocytochemistry analysis confirmed keratinocytes differentiation pattern and their normal phenotype on PCL/QSM/PEG. Our study demonstrates, QSM as a differentiation/growth-promoting biological factor can be a proper candidate for design of wound dressings and skin tissue-engineered substrates containing cell.