Combination of Controlled Release Platelet‐Rich Plasma Alginate Beads and Bone Morphogenetic Protein‐2 Genetically Modified Mesenchymal Stem Cells for Bone Regeneration

Abstract

Background Platelet rich plasma (PRP) consists of platelet derived growth factor (PDGF) and Transforming growth factor-beta (TGF-β) that increase cell proliferation of mesenchymal stem cells (MSCs), whereas, bone morphogenic Protein-2 (BMP2) promotes osteogenic differentiation of MSCs. However, the high degradation rate of fibrin leads to the dissociation of cytokines even before the process of bone regeneration has begun. Hence, for the first time, we studied the combined effect of sustained released PRP from alginate beads on BMP2 modified MSCs osteogenic differentiation in vitro and of sustained PRP alone on a fracture defect model ex vivo as well as its effect on the calvarial suture closure. Methods After optimizing the concentration of alginate for the microspheres, the osteogenic and mineralization effect of PRP and BMP2 in combinations on MSCs was studied. A self-setting alginate hydrogel carrying PRP was tested on a femur defect model ex-vivo. The effect of PRP was studied on the closure of the embryonic (E15) mouse calvaria sutures ex vivo. Results Increase of PRP concentration promoted cellular proliferation of MSCs. 2.5%–10% of PRP displayed gradually increased ALP activity on the cells in a dose dependent manner. Sustained release PRP and BMP2 demonstrated a significantly higher ALP and mineralization activity (p<0.05). The radiographs of alginate hydrogel with PRP treated bone demonstrated a nearly complete healing of the fracture and the histological sections of the embryonic calvaria revealed that PRP leads to suture fusion. Conclusions Sustained release of PRP along with BMP2 gene modified MSCs can significantly promote bone regeneration.

Protective effect of catalpol on nicotine-induced injury of alveolar bone and associated underlying mechanisms

“…The present study used a periodontal disease model and induced alveolar bone injury via nicotine infusion, and demonstrated that nicotine caused the loss of alveolar bone. Extracted from a traditional Chinese medicine, catalpol exhibits multiple pharmaceutical activities and serves important roles as an anti-inflammatory agent and mediator of oxidation-reduction homeostasis (22). The present study demonstrated that catalpol may alleviate the loss of alveolar bone in a nicotine-induced rat alveolar bone injury model.…”

Fabrication and properties of an injectable sodium alginate/PRP composite hydrogel as a potential cell carrier for cartilage repair

“…Additionally, during the activation of PRP, coagulation can be triggered leading to polymerization of fibrinogen with formation of fibrin, which is an appealing source of natural polymer as component of biomaterials or employed alone as 3D scaffold for tissue engineering (Lee, ; Ma, Titan, Stafford, Zheng, & Levenston, ; Xie et al, ). Activated PRP has been also used either as medium supplement to promote chondrogenic differentiation of marrow stromal cells (MSCs) encapsulated in a 3D alginate scaffold (Beigi et al, ) or incorporated into alginate beads for promoting osteogenic (Fernandes et al, ) or chondrogenic differentiation (Tang et al, ). However, so far, no studies exist about the use of PRP as component of hydrogels with the question whether PRP is activated during gel formation, which should lead to release of growth factors that enhance MSC response and formation of a fibrin network that affects the mechanical properties of the composite SA/PRP hydrogel.…”

“…Additionally, during the activation of PRP, coagulation can be triggered leading to polymerization of fibrinogen with formation of fibrin, which is an appealing source of natural polymer as component of biomaterials or employed alone as 3D scaffold for tissue engineering (Lee, 2013;Ma, Titan, Stafford, Zheng, & Levenston, 2012;Xie et al, 2012). Activated PRP has been also used either as medium supplement to promote chondrogenic differentiation of marrow stromal cells (MSCs) encapsulated in a 3D alginate scaffold (Beigi et al, 2018) or incorporated into alginate beads for promoting osteogenic (Fernandes et al, 2016) China. Preparation of hUCB PRP was conducted according to a previously published method with some modification (Shoji Fukuda et al, 2015).…”

Periodontal tissue engineering: current strategies and the role of platelet rich hemoderivatives

“…77 The incorporation of PRP into hydrogels seems to be an adequate alternative. 68,81,82 Fernandes and co-workers 81 showed that the encapsulation of PRP into alginate microbeads promoted the sustained release of PDGF. Moreover, this system promoted faster obliteration of the sagittal and coronal cranial sutures of mice embryonic calvaria.…”

“…Moreover, this system promoted faster obliteration of the sagittal and coronal cranial sutures of mice embryonic calvaria. 81 Finally, the coating of dental metallic implants with PRP proteins improves their tissue integration. For instance, the osteointegration of Ti implants was enhanced by coating the implant surface with PRGF prior to insertion into the alveolus.…”