Expanded skeletal stem and progenitor cells promote and participate in induced bone regeneration at subcritical BMP-2 dose

Papageorgiou, Panagiota; Vallmajó-Martín, Queralt; Kisielow, Malgorzata; Sancho-Puchades, Alejandro; Kleiner, Esther; Ehrbar, Martin

doi:10.1016/j.biomaterials.2019.119278

Cited by 31 publications

(25 citation statements)

References 62 publications

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“…The use of MMP‐sensitive substrates and the cross‐linking in the presence of a lysine‐tagged RGD can be varied to turn TG‐PEG into a cell substrate to accurately match specific demands ( Figure A). As shown in earlier studies, the design of these TG‐PEG hydrogels allows their modular tailoring with respect to presentation of cell adhesion sites, proteolytic degradability, or mechanical properties (Figure B) 10c,11e,13. When formed at low initial polymer concentration (1.7–2.3% w/v), TG‐PEG hydrogels were stable and did not swell in a physiological buffer (Figure C).…”

Section: Resultsmentioning

confidence: 72%

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

et al. 2020

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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.

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Section: Resultsmentioning

confidence: 72%

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

et al. 2020

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“…Due to the complex interaction among mineralized collagen fibril, ACP, and SA, the IWBLHs were structurally stable and weight loss were less than 20% over 4 weeks in PBS, indicating that IWBLHs could provide an integrated architecture for cell. Although numerous hydrogels have been employed in bone regeneration, the majority of them are only designed to act as the scaffold carrying and delivering growth factor to promote osteogenesis (Chen et al, 2019;Pan et al, 2019;Papageorgiou et al, 2019) rather than mimicking the complex bone microenvironment. In our study, an alginate-based hydrogel was employed with the incorporation of ACP and mineralized collagen fibril.…”

Section: Discussionmentioning

confidence: 99%

The Injectable Woven Bone-Like Hydrogel to Perform Alveolar Ridge Preservation With Adapted Remodeling Performance After Tooth Extraction

Xie

Liao

et al. 2020

Front. Bioeng. Biotechnol.

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Grafting bone substitute is paramount to prevent the alveolar ridge resorption after tooth extraction and facilitate the subsequent implant treatment. An ideal bone substitute should acquire the excellent osteogenic property, more importantly, possess the suitable remodeling rate in balance with bone formation and desirable clinical manageability. However, none of bone substitute is simultaneously characterized by these features, and currently, the limited remodeling property leads to the excessive waiting time before implantation. Enlightened by woven bone, the transitional tissue that is able to induce osteogenesis during bone healing could be easily remodeled within a short period and depend on the favorable injectability of hydrogel, an injectable woven bone-like hydrogel (IWBLH) was constructed in this study to address the above problems. To mimic the component and hierarchical structure of woven bone, amorphous calcium phosphate (ACP) and mineralized collagen fibril were synthesized and compounded with alginate to form IWBLHs with various ratio. Screened by physiochemical characterization and in vitro biological assays, an optimal IWBLH was selected and further explored in rat model of tooth extraction. Compared with the most widely used bone substitute, we showed that IWBLH could be easily handled to fully fill the tooth socket, perform a comparable function to prevent the alveolar bone resorption, and completely remodeled within 4 weeks. This IWBLH stands as a promising candidate for alveolar ridge preservation (ARP) in future.

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“…MSCs) differentiate into osteoblasts (intramembranous osteogenesis) and chondrogenic cells (endochondral osteogenesis) under the regulation of TGF-including BMPs, which are the most effective growth factors in this process. [10,11] Among the BMPs, BMP-2 and BMP-7 are two most commonly www.advancedsciencenews.com www.advhealthmat.de used growth factors used in bone regeneration and act as powerful activators for osteogenic differentiation of MSCs. [11,124] Bone repair in response to BMP-2 is dose-dependent.…”

Section: Incorporated Growth Factors For Enhanced Cell Recruitment Differentiation and Vascularization Of Graftsmentioning

confidence: 99%

“…[11,124] Bone repair in response to BMP-2 is dose-dependent. [10] Under the optimal combination with adequate matrix, the release of BMPs can be prolonged and the matrix subsequently provides the mechanical support for the invasion of the osteoprogenitor cells when necessary. [125] Collagen sponges appear as a widely used carrier for BMP-2.…”

Section: Incorporated Growth Factors For Enhanced Cell Recruitment Differentiation and Vascularization Of Graftsmentioning

confidence: 99%

“…The combination of scaffolds and growth factors may enhance the regenerative performance of bone substitutes after in vivo implantation. [10,12] In the past decades, stem cell-based therapy has emerged as a novel branch in bone regenerative medicine. Stem cells such as bone marrow-derived stem cells (BMSCs), adipose-derived cells (ADSCs), and periosteum-derived stem cells (PDSCs) are of clinical interest owing to their multi-lineage differentiation ability and relatively abundant sources.…”

Section: Introductionmentioning

confidence: 99%

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Advanced Strategies of Biomimetic Tissue‐Engineered Grafts for Bone Regeneration

Xie

Liang

et al. 2021

Adv Healthcare Materials

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The failure to repair critical-sized bone defects often leads to incomplete regeneration or fracture non-union. Tissue-engineered grafts have been recognized as an alternative strategy for bone regeneration due to their potential to repair defects. To design a successful tissue-engineered graft requires the understanding of physicochemical optimization to mimic the composition and structure of native bone, as well as the biological strategies of mimicking the key biological elements during bone regeneration process. This review provides an overview of engineered graft-based strategies focusing on physicochemical properties of materials and graft structure optimization from macroscale to nanoscale to further boost bone regeneration, and it summarizes biological strategies which mainly focus on growth factors following bone regeneration pattern and stem cell-based strategies for more efficient repair. Finally, it discusses the current limitations of existing strategies upon bone repair and highlights a promising strategy for rapid bone regeneration.

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Expanded skeletal stem and progenitor cells promote and participate in induced bone regeneration at subcritical BMP-2 dose

Cited by 31 publications

References 62 publications

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

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

The Injectable Woven Bone-Like Hydrogel to Perform Alveolar Ridge Preservation With Adapted Remodeling Performance After Tooth Extraction

Advanced Strategies of Biomimetic Tissue‐Engineered Grafts for Bone Regeneration

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