Smart Hydrogels for the Augmentation of Bone Regeneration by Endogenous Mesenchymal Progenitor Cell Recruitment

Abstract

The treatment of bone defects with recombinant bone morphogenetic protein‐2 (BMP‐2) requires high doses precluding broad clinical application. Here, a bioengineering approach is presented that strongly improves low‐dose BMP‐2‐based bone regeneration by mobilizing healing‐associated mesenchymal progenitor cells (MPCs). Smart synthetic hydrogels are used to trap and study endogenous MPCs trafficking to bone defects. Hydrogel‐trapped and prospectively isolated MPCs differentiate into multiple lineages in vitro and form bone in vivo. In vitro screenings reveal that platelet‐derived growth factor BB (PDGF‐BB) strongly recruits prospective MPCs making it a promising candidate for the engineering of hydrogels that enrich endogenous MPCs in vivo. However, PDGF‐BB inhibits BMP‐2‐mediated osteogenesis both in vitro and in vivo. In contrast, smart two‐way dynamic release hydrogels with fast‐release of PDGF‐BB and sustained delivery of BMP‐2 beneficially promote the healing of bone defects. Collectively, it is shown that modulating the dynamics of endogenous progenitor cells in vivo by smart synthetic hydrogels significantly improves bone healing and holds great potential for other advanced applications in regenerative medicine.

Red and Yellow Injectable Platelet-Rich Fibrin Demonstrated Differential Effects on Periodontal Ligament Stem Cell Proliferation, Migration, and Osteogenic Differentiation

“…In contrast, PDGF receptor signaling regulates mesenchymal stem cell proliferation and migration [ 34 , 35 ], and potentially decreases the expression of collagen type I and bone sialoprotein, which are osteogenic marker genes [ 33 ]. Similar results were reported in previous studies when an excessive concentration of the signaling molecules from PRF inhibited or had no effect on mesenchymal stem cell osteogenic differentiation [ 23 , 28 ]. Furthermore, limited osteogenic differentiation has been shown when an enriched platelet product was used to induce mesenchymal stem cell differentiation [ 23 , 36 , 37 ].…”

“…However, the red i-PRF demonstrated a greater effect compared with the yellow i-PRF. The growth factor concentration in the release used in this study was measured and presented in our previous report [ 15 ], and these results correspond to earlier studies that the red i-PRF, containing more platelets and cells, released more VEGF and PDGF, which are potent stimulators of cell proliferation and migration [ 15 , 27 , 28 ]. Here, the advantages of leukocytes in the red i-PRF are also noteworthy.…”

“…Previous results [ 15 ] corresponded with ours, showing that the release from red i-PRF during the first 3 d was suitable for recruiting the cells and leading to enhanced PDLSC proliferation, but not osteogenic differentiation. The slightly inferior osteogenic differentiation is likely to increase clinical bone regeneration because it can ensure that an adequate number of cells are recruited to the bone graft site, because healing failed without sufficient mesenchymal stem cells [ 28 ]. At the early stage, the wound area can localize more cells or stem cells with the use of red i-PRF, while, at the late stage, a microenvironment appropriate for cell differentiation and tissue formation might be established if the release from red i-PRF declines.…”

Synergistic Fabrication of Dose–Response Chitosan/Dextran/β-Glycerophosphate Injectable Hydrogel as Cell Delivery Carrier for Cardiac Healing After Acute Myocardial Infarction

“…Even though, the stem cells are features of distinguishable toward the immuno-modulation and immuno-suppression properties. [25][26][27][28] Synergic methods, as well, a promising strategy and biocompatible, biodegradable materials are required for efficient cardiac stem cells transplantation to associate the treatment for AMI. Hence, a pouch-like hydrogel materials like collagen, gelatin, and fibroin can serve as a potential and medically advantageous candidate in drug delivery systems, cell therapy, creation and regeneration of muscle tissues, and controlled release of systems.…”

“…Even though, the stem cells are features of distinguishable toward the immuno-modulation and immuno-suppression properties. 25 - 28 …”