Regeneration of Volumetric Muscle Loss Using MSCs Encapsulated in PRP-Derived Fibrin Microbeads.

Volumetric muscle loss (VML) is one of the major types of soft tissue injury frequently encountered worldwide. In case of VML, the endogenous regenerative capacity of the skeletal muscle tissue is usually not sufficient for complete healing of the damaged area resulting in permanent functional musculoskeletal impairment. Therefore, the development of new tissue engineering approaches that will enable functional skeletal muscle regeneration by overcoming the limitations of current clinical treatments for VML injuries has become a critical goal. Platelet-rich plasma (PRP) is an inexpensive and relatively effective blood product with a high concentration of platelets containing various growth factors and cytokines involved in wound healing and tissue regeneration. Due to its autologous nature, PRP has been a safe and widely used treatment option for various wound types for many years. Recently, PRP-based biomaterials have emerged as a promising approach to promote muscle tissue regeneration upon injury. This chapter describes the use of PRP-derived fibrin microbeads as a versatile encapsulation matrix for the localized delivery of mesenchymal stem cells and growth factors to treat VML using tissue engineering strategies.

Magnetic biocomposite scaffold based on decellularized tendon ECM and MNP-deposited halloysite nanotubes: physicochemical, thermal, rheological, mechanical andin vitrobiological evaluations.

The development of new three-dimensional biomaterials with advanced versatile properties is critical to the success of tissue engineering (TE) applications. Here, (a) bioactive decellularized tendon extracellular matrix (dECM) with a sol-gel transition feature at physiological temperature, (b) halloysite nanotubes (HNT) with known mechanical properties and bioactivity, and (c) magnetic nanoparticles (MNP) with superparamagnetic and osteogenic properties were combined to develop a new scaffold that could be used in prospective bone TE applications. Deposition of MNPs on HNTs resulted in magnetic nanostructures without agglomeration of MNPs. A completely cell-free, collagen- and glycosaminoglycan- rich dECM was obtained and characterized. dECM-based scaffolds incorporated with 1%, 2% and 4% MNP-HNT were analysed for their physical, chemical, andin vitrobiological properties. Fourier-transform infrared spectroscopy, x-ray powder diffractometry and vibrating sample magnetometry analyses confirmed the presence of dECM, HNT and MNP in all scaffold types. The capacity to form apatite layer upon incubation in simulated body fluid revealed that dECM-MNP-HNT is a bioactive material. Combining dECM with MNP-HNT improved the thermal stability and compressive strength of the macroporous scaffolds upto 2% MNP-HNT.In vitrocytotoxicity and hemolysis experiments showed that the scaffolds were essentially biocompatible. Human bone marrow mesenchymal stem cells adhered and proliferated well on the macroporous constructs containing 1% and 2% MNP-HNT; and remained metabolically active for at least 21 din vitro. Collectively, the findings support the idea that magnetic nanocomposite dECM scaffolds containing MNP-HNT could be a potential template for TE applications.

Biomimetic mineralization of platelet lysate/oxidized dextran cryogel as a macroporous 3D composite scaffold for bone repair.

Scaffold development approaches using autologous sources for tissue repair are of great importance in obtaining bio-active/-compatible constructs. Platelet-rich plasma (PRP) containing various growth factors and platelet lysate (PL) derived from PRP are autologous products that have the potential to accelerate the tissue repair response by inducing a transient inflammatory event. Considering the regenerative capacity of PRP and PL, PRP/PL-based scaffolds are thought to hold great promise for tissue engineering as a natural source of autologous growth factors and a provider of mechanical support for cells. Here, a bio-mineralized PRP-based scaffold was developed using oxidized dextran (OD) and evaluated for future application in bone tissue engineering. Prepared PL/OD scaffolds were incubated in simulated body fluid (SBF) for 7, 14 and 21 d periods. Mineralized PL/OD scaffolds were characterized using Fourier transform infrared spectroscopy, x-ray diffraction spectroscopy, scanning electron microscopy (SEM), thermogravimetric analysis, porosity and compression tests. SEM and energy-dispersive x-ray spectroscopy analyses revealed mineral accumulation on the PL/OD scaffold as a result of SBF incubation.In vitrocytotoxicity andin vitrohemolysis tests revealed that the scaffolds were non-toxic and hemocompatible. Additionally, human osteoblasts (hOBs) exhibited good attachment and spreading behavior on the scaffolds and maintained their viability throughout the culture period. The alkaline phosphatase activity assay and calcium release results revealed that PL/OD scaffolds preserved the osteogenic properties of hOBs. Overall, findings suggest that mineralized PL/OD scaffold may be a promising scaffold for bone tissue engineering.

Decellularized Bone Matrix/45S5 Bioactive Glass Biocomposite Hydrogel-Based Constructs with Angiogenic and Osteogenic Properties: Ex Ovo and Ex Vivo Evaluations.

Decellularized extracellular matrix is often used to create an in vivo-like environment that supports cell growth and proliferation, as it reflects the micro/macrostructure and molecular composition of tissues. On the other hand, bioactive glasses (BG) are surface-reactive glass-ceramics that can convert to hydroxyapatite in vivo and promote new bone formation. This study is designed to evaluate the key properties of a novel angiogenic and osteogenic biocomposite graft made of bovine decellularized bone matrix (DBM) hydrogel and 45S5 BG microparticles (10 and 20 wt%) to combine the existing superior properties of both biomaterial classes. Morphological, physicochemical, mechanical, and thermal characterizations of DBM and DBM/BG composite hydrogels are performed. Their in vitro biocompatibility is confirmed by cytotoxicity and hemocompatibility analyses. Ex vivo chick embryo aortic arch and ex ovo chick chorioallantoic membrane (CAM) assays reveal that the present pro-angiogenic property of DBM hydrogels is enhanced by the incorporation of BG. Histochemical stainings (Alcian blue and Alizarin red) and digital image analysis of ossification on hind limbs of embryos used in the CAM model reveal the osteogenic potential of biomaterials. The findings support the notion that the developed DBM/BG composite hydrogel constructs have the potential to be a suitable graft for bone repair.