Functionality of lyophilized osteoinductive EVs: a mechanistic study.

Introduction: Mesenchymal stem cell-derived extracellular vesicles (MSC EVs) hold significant promise for regenerative medicine. Lyophilization of EVs significantly enhances their translational potential. While, lyophilized EVs have been studied from a morphological perspective, the functional stability of these EVs and their cargo following lyophilization need to be mechanistically investigated.

Comparative Osteogenesis of Three Clinical Bone Graft Materials: An In Vivo Study.

Purpose: To investigate bone regeneration among three different bone graft materials in a rat calvarum model.

Materials And Methods: A total of 24 rats had two 5-mm defects placed per calvarial. Rats were divided into four groups: bovine xenograft (XG), demineralized bone matrix (DBM), mineralized bone graft (MBG), and collagen membrane control (CC).

Evaluation of nanoscale versus hybrid micro/nano surface topographies for endosseous implants.

We examined the effect of a nanoscale titanium surface topography (D) versus two hybrid micro/nanoscale topographies (B and OS) on adherent mesenchymal stem cells (MSCs) and bone marrow derived macrophages (BMMs) function in cell culture and in vivo. In the in vitro study, compared to OS and B surfaces, D surface induced earlier and greater cell spreading, and earlier and profound mRNA expression of RUNX2, Osterix and BMP2 in MSCs. D surface induced earlier and higher expression of RUNX2 and BMP2 and lower expression of inflammatory genes in implant adherent cells in vivo.

Micro RNA based MSC EV engineering: Targeting the BMP2 cascade for bone repair.

Mesenchymal stem cell derived extracellular vesicles (MSC EVs) possess excellent immunomodulatory and therapeutic properties. While beneficial, from a translational perspective, extracellular vesicles with consistent functionality and target specificity are required to achieve the goals of precision medicine and tissue engineering. Prior research has identified that the miRNA composition of mesenchymal stem cell derived extracellular vesicles contributes significantly towards extracellular vesicles functionality.

Extracellular Vesicles From TNFα Preconditioned MSCs: Effects on Immunomodulation and Bone Regeneration.

Mesenchymal stem cells show remarkable versatility and respond to extracellular and micro environmental cues by altering their phenotype and behavior. In this regard, the MSC's immunomodulatory properties in tissue repair are well documented. The paracrine effects of MSCs in immunomodulation are, in part, attributable to their secreted extracellular vesicles (EVs).

3D Encapsulation and tethering of functionally engineered extracellular vesicles to hydrogels.

Mesenchymal stem cell (MSC) derived extracellular vesicles (EVs) in their naïve and engineered forms have emerged as potential alternatives to stem cell therapy. While they have a defined therapeutic potential, the spatial and temporal control of their activity in vivo remains a challenge. The objective of this study was to devise a methodology to encapsulate EVs in 3D hydrogels for prolonged delivery.

The importance of cellular and exosomal miRNAs in mesenchymal stem cell osteoblastic differentiation.

The differentiation of osteoblasts is under complex regulation that includes autocrine and paracrine signaling from MSCs. Exosomes are important components of the MSC secretome and their cargo contains numerous miRNAs. In this study, the importance of MSC miRNAs in modulation of osteoblastic differentiation was examined by global reduction of miRNA biosynthesis in Dicer knock down hMSCs.

Macrophage Control of Incipient Bone Formation in Diabetic Mice.

Both soft and hard tissue wound healing are impaired in diabetes. Diabetes negatively impacts fracture healing, bone regeneration and osseointegration of endosseous implants. The complex physiological changes associated with diabetes often manifest in immunological responses to wounding and repair where macrophages play a prominent role in determining outcomes.

Engineering a Self-Assembling Leucine Zipper Hydrogel System with Function-Specific Motifs for Tissue Regeneration.

Protein-based self-assembling hydrogels can exhibit remarkably tunable properties as a scaffold for regenerative medicine applications. In this study, we sought to develop a leucine zipper (LZ) based self-assembling hydrogel with function-specific motifs for tissue-specific regeneration. As a proof-of-concept approach, we incorporated (a) calcium-binding domains ESQES and QESQSEQS derived from dentin matrix protein 1 (DMP1) and (b) an heparin-binding domain adjacent preceded by an MMP2 (matrix metalloprotease 2) cleavage site to facilitate loading of heparin binding growth factors, such as BMP-2, VEGF, and TGF-β1, and their release in vivo by endogenous MMP2 proteolytic cleavage.

Bone regeneration is mediated by macrophage extracellular vesicles.

Multiple local and systemic factors including inflammation influence bone regeneration. Several lines of evidence demonstrate that macrophages contribute to the immunological regulation of MSC and osteoblast function during bone regeneration. Recent studies demonstrate that macrophage polarization influences this regulatory process.

Functionally engineered extracellular vesicles improve bone regeneration.

Lineage specific differentiation of host mesenchymal stem cells (MSCs) is a necessary step for bone repair/regeneration. Clinically, growth factors such as bone morphogenetic protein 2 (BMP2) are used to enhance/hasten this process to heal critical sized defects. However, the clinical application of such growth factors is fraught with dosage challenges as well as immunological and ectopic complications.

Evaluating the Endocytosis and Lineage-Specification Properties of Mesenchymal Stem Cell Derived Extracellular Vesicles for Targeted Therapeutic Applications.

Mesenchymal stem cells (MSCs) are multipotent cells with regenerative and immunomodulatory properties. Several aspects of MSC function have been attributed to the paracrine effects of MSC derived extracellular vesicles (EVs). Although MSC EVs show great promise for regenerative medicine applications, insights into their uptake mechanisms by different target cells and the ability to control MSC EV properties for defined function have remained elusive knowledge gaps.

A Role for Exosomes in Craniofacial Tissue Engineering and Regeneration.

Tissue engineering and regenerative medicine utilize mesenchymal stem cells (MSCs) and their secretome in efforts to create or induce functional tissue replacement. Exosomes are specific extracellular vesicles (EVs) secreted by MSCs and other cells that carry informative cargo from the MSC to targeted cells that influence fundamental cellular processes including apoptosis, proliferation, migration, and lineage-specific differentiation. In this report, we review the current knowledge regarding MSC exosome biogenesis, cargo and function.