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![Vascularization approaches for bone tissue engineering. (a) In vitro prevascularization techniques induce cell-seeded scaffolds to form vasculature via exogenous growth factors. Following implantation in the bone defect, these engineered capillaries will in theory rapidly anastomose to perfuse the entire graft. (b) In vivo ectopic prevascularization involves implantation of a cell-seeded scaffold into a highly vascularized bed, such as muscle or arteriovenous (AV) loop, to allow extensive vascular ingrowth. The graft is transplanted as a free flap to the bone defect and surgically anastomosed with the surrounding vessels to immediately perfuse the graft. (c) In vivo orthotopic vascularization involves direct implantation of scaffolds into the bone defect for in situ tissue development. Cells seeded into the scaffolds can be aggregated to improve cell survival and endogenous cell signaling. Scaffolds can be functionalized for the controlled release of growth factors (stars) that induce bone and vascular growth. Reprinted by permission from Elsevier Ltd., Current Opinion in Chemical Engineering, Hutton & Grayson [22], copyright © 2014.](publication/289586397/figure/fig5/AS:1086742492905500@1636111009345/Vascularization-approaches-for-bone-tissue-engineering-a-In-vitro-prevascularization.jpg)
Vascularization approaches for bone tissue engineering. (a) In vitro prevascularization techniques induce cell-seeded scaffolds to form vasculature via exogenous growth factors. Following implantation in the bone defect, these engineered capillaries will in theory rapidly anastomose to perfuse the entire graft. (b) In vivo ectopic prevascularization involves implantation of a cell-seeded scaffold into a highly vascularized bed, such as muscle or arteriovenous (AV) loop, to allow extensive vascular ingrowth. The graft is transplanted as a free flap to the bone defect and surgically anastomosed with the surrounding vessels to immediately perfuse the graft. (c) In vivo orthotopic vascularization involves direct implantation of scaffolds into the bone defect for in situ tissue development. Cells seeded into the scaffolds can be aggregated to improve cell survival and endogenous cell signaling. Scaffolds can be functionalized for the controlled release of growth factors (stars) that induce bone and vascular growth. Reprinted by permission from Elsevier Ltd., Current Opinion in Chemical Engineering, Hutton & Grayson [22], copyright © 2014.
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Mesenchymal stem cells (MSCs) have been the subject of many studies in recent years, ranging from basic science that looks into MSCs properties to studies that aim for developing bioengineered tissues and organs. Adult bone marrow-derived mesenchymal stem cells (BM-MSCs) have been the focus of most studies due to the inherent potential of these cel...
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Nowadays, there has been immense progress in developing materials to support transplanted cells. Nevertheless, the complexity of tissues is far beyond what is found in the most advanced scaffolds. This article reviews the types of biomaterials and their resulting scaffolds in the bio-engineering of bone and tissues by presenting an overview of the...
Citations
... In summary, ASCs offer the advantages of easy access and abundant supply [110]. While ASCs offer benefits such as easy access and ample supply, ex vivo expansion is typically necessary to minimize contamination with other cell types. ...
Osteoporosis is a skeletal disorder marked by compromised bone integrity, predisposing individuals, particularly older adults and postmenopausal women, to fractures. The advent of bioceramics for bone regeneration has opened up auspicious pathways for addressing osteoporosis. Research indicates that bioceramics can help bones grow back by activating bone morphogenetic protein (BMP), mitogen-activated protein kinase (MAPK), and wingless/integrated (Wnt)/β-catenin pathways in the body when combined with stem cells, drugs, and other supports. Still, bioceramics have some problems, such as not being flexible enough and prone to breaking, as well as difficulties in growing stem cells and discovering suitable supports for different bone types. While there have been improvements in making bioceramics better for healing bones, it is important to keep looking for new ideas from different areas of medicine to make them even better. By conducting a thorough scrutiny of the pivotal role bioceramics play in facilitating bone regeneration, this review aspires to propel forward the rapidly burgeoning domain of scientific exploration. In the end, this appreciation will contribute to the development of novel bioceramics that enhance bone regrowth and offer patients with bone disorders alternative treatments.
... In summary, ASCs offer the advantages of easy access and abundant supply [113]. While ASCs offer benefits such as easy access and ample supply, ex vivo expansion is typically necessary to minimize contamination with other cell types. ...
Osteoporosis is a bone condition where bones become weaker, leading to fractures, especially in older adults and postmenopausal women. Bioceramics for bone regeneration have indeed emerged as a promising solution for conditions like osteoporosis. Choosing the right bioceramic depends on how quickly it dissolves, how strong it is, and whether the body will react to it. Studies show that bioceramics can help bones grow back by activating (bone morphogenetic protein) BMP, (mitogen-activated protein kinase) MAPK, and Wingless/integrated (Wnt)/β-catenin pathways in the body when combined with stem cells, drugs, and supports. However, bioceramics have some problems like not being flexible enough and being prone to breaking, as well as difficulties in growing stem cells and finding the right supports for different bone types. While there has been progress in improving bioceramics for bone healing, we need to keep looking for new ideas from other areas of medicine to keep improving them. This review aims to add to the expanding field of scientific research by offering a detailed look at how bioceramics and growth factors contribute to bone regeneration. Ultimately, this knowledge will help in creating new types of bioceramics that can improve bone regrowth, providing new treatment options for people with bone diseases.
... BMSCs, multifunctional stem cells within bone marrow, possess the capability to differentiate into osteoblasts upon stimulation [43][44][45]. These stem cells discern and adapt to their microenvironment by modulating their actions [46][47][48][49]. ...
Macrophage-mediated bone immune responses significantly influence the repair of bone defects when utilizing tissue-engineered scaffolds. Notably, the scaffolds' physical structure critically impacts macrophage polarization. The optimal pore size for facilitating bone repair remains a topic of debate due to the imprecision of traditional methods in controlling scaffold pore dimensions and spatial architecture. In this investigation, we utilized fused deposition modeling (FDM) technology to fabricate high-precision porous polycaprolactone (PCL) scaffolds, aiming to elucidate the impact of pore size on macrophage polarization. We assessed the scaffolds' mechanical attributes and biocompatibility. Real-time quantitative reverse transcription polymerase chain reaction (RT-qPCR) was used to detect the expression levels of macrophage-related genes, and enzyme linked immunosorbent assay (ELISA) for cytokine secretion levels. In vitro osteogenic capacity was determined through alkaline phosphatase (ALP) and alizarin red staining (ARS). Our findings indicated that macroporous scaffolds enhanced macrophage adhesion and drove their differentiation towards the M2 phenotype. This led to the increased production of anti-inflammatory factors and a reduction in pro-inflammatory agents, highlighting the scaffolds' immunomodulatory capabilities. Moreover, conditioned media from macrophages cultured on these macroporous scaffolds bolstered the osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs), exhibiting superior osteogenic differentiation potential. Consequently, FDM-fabricated PCL scaffolds, with precision-controlled pore sizes, present promising prospects as superior materials for bone tissue engineering, leveraging the regulation of macrophage polarization.
... Stem cell-based dental and skeletal tissue regeneration is a promising therapeutic approach [11], and bone marrow mesenchymal stem cells (BM-MSCs) are one of the most investigated MSCs for bone regeneration due to their superior osteogenic capabilities [12][13][14][15][16]. BM-MSCs have been through several clinical trials for treating knee osteoarthritis where they improved clinical and radiographic outcomes [17][18][19][20]. ...
Type 2 diabetes mellitus (T2DM) represents a significant health problem globally and is linked to a number of complications such as cardiovascular disease, bone fragility and periodontitis. Autologous bone marrow mesenchymal stem cells (BM-MSCs) are a promising therapeutic approach for bone and periodontal regeneration; however, the effect of T2DM on the expression of osteogenic and periodontal markers in BM-MSCs is not fully established. Furthermore, the effect of the presence of comorbidities such as diabetes and osteoarthritis on BM-MSCs is also yet to be investigated. In the present study, BM-MSCs were isolated from osteoarthritic knee joints of diabetic and nondiabetic donors. Both cell groups were compared for their clonogenicity, proliferation rates, MSC enumeration and expression of surface markers. Formation of calcified deposits and expression of osteogenic and periodontal markers were assessed after 1, 2 and 3 weeks of basal and osteogenic culture. Diabetic and nondiabetic BM-MSCs showed similar clonogenic and growth potentials along with comparable numbers of MSCs. However, diabetic BM-MSCs displayed lower expression of periostin (POSTN) and cementum protein 1 (CEMP-1) at Wk3 osteogenic and Wk1 basal cultures, respectively. BM-MSCs from T2DM patients might be suitable candidates for stem cell-based therapeutics. However, further investigations into these cells’ behaviours in vitro and in vivo under inflammatory environments and hyperglycaemic conditions are still required.
... Bone marrow mesenchymal stromal cells (BMSCs) are one of the most commonly used seed cells. The osteogenic potential of BMSCs is the premise of their applications in bone regeneration [1]. Additionally, the crosstalk between BMSCs and immune cells like macrophages has been recognized as a critical element in achieving ideal bone tissue repair [2]. ...
Background:
Bone marrow mesenchymal stromal cells (BMSCs) are the commonly used seed cells in tissue engineering. Aryl hydrocarbon receptor (AhR) is a transcription factor involved in various cellular processes. However, the function of constitutive AhR in BMSCs remains unclear.
Aim:
To investigate the role of AhR in the osteogenic and macrophage-modulating potential of mouse BMSCs (mBMSCs) and the underlying mechanism.
Methods:
Immunochemistry and immunofluorescent staining were used to observe the expression of AhR in mouse bone marrow tissue and mBMSCs. The overexpression or knockdown of AhR was achieved by lentivirus-mediated plasmid. The osteogenic potential was observed by alkaline phosphatase and alizarin red staining. The mRNA and protein levels of osteogenic markers were detected by quantitative polymerase chain reaction (qPCR) and western blot. After coculture with different mBMSCs, the cluster of differentiation (CD) 86 and CD206 expressions levels in RAW 264.7 cells were analyzed by flow cytometry. To explore the underlying molecular mechanism, the interaction of AhR with signal transducer and activator of transcription 3 (STAT3) was observed by co-immunoprecipitation and phosphorylation of STAT3 was detected by western blot.
Results:
AhR expressions in mouse bone marrow tissue and isolated mBMSCs were detected. AhR overexpression enhanced the osteogenic potential of mBMSCs while AhR knockdown suppressed it. The ratio of CD86+ RAW 264.7 cells cocultured with AhR-overexpressed mBMSCs was reduced and that of CD206+ cells was increased. AhR directly interacted with STAT3. AhR overexpression increased the phosphorylation of STAT3. After inhibition of STAT3 via stattic, the promotive effects of AhR overexpression on the osteogenic differentiation and macrophage-modulating were partially counteracted.
Conclusion:
AhR plays a beneficial role in the regenerative potential of mBMSCs partially by increasing phosphorylation of STAT3.
... Millions of bone grafting surgical procedures for the partial excision of bone are performed worldwide. 1,2 In general, autograft transplantation and allograft transplantation are the standard clinical procedures. 1 However, they are associated with postoperative complications and availability problems. 1 In this context, tissue engineering is a potential alternative for tissue transplants and constitutes a novel approach in regenerative medicine that involves using natural and synthetic materials in combination with stem cells to repair the damaged areas. ...
... 1,2 In general, autograft transplantation and allograft transplantation are the standard clinical procedures. 1 However, they are associated with postoperative complications and availability problems. 1 In this context, tissue engineering is a potential alternative for tissue transplants and constitutes a novel approach in regenerative medicine that involves using natural and synthetic materials in combination with stem cells to repair the damaged areas. ...
... 1,2 In general, autograft transplantation and allograft transplantation are the standard clinical procedures. 1 However, they are associated with postoperative complications and availability problems. 1 In this context, tissue engineering is a potential alternative for tissue transplants and constitutes a novel approach in regenerative medicine that involves using natural and synthetic materials in combination with stem cells to repair the damaged areas. 3,4 The bone tissue engineering strategy consists of 3 essential components: scaffold, mesenchymal stem cells (MSCs) and bioactive growth factors. ...
Tissue engineering has become one of the most studied medical fields and appears to be promising for the regeneration of injured bone tissues. Even though the bone has self-remodeling properties, bone regeneration may be required in some cases. Current research concerns materials employed to develop biological scaffolds with improved features as well as complex preparation techniques. Several attempts have been made to achieve compatible and osteoconductive materials with good mechanical strength in order to provide structural support. The application of biomaterials and mesenchymal stem cells (MSCs) is a promising prospect for bone regeneration. Recently, various cells have been utilized alone or in combination with biomaterials to accelerate bone repair in vivo. However, the question of what cell source is the best for use in bone engineering remains open. This review focuses on studies that evaluated bone regeneration using biomaterials with MSCs. Different types of biomaterials for scaffold processing, ranging from natural and synthetic polymers to hybrid composites, are presented. These constructs demonstrated an enhanced ability to regenerate the bone in vivo using animal models. Additionally, future perspectives in tissue engineering, such as the MSC secretome, that is the conditioned medium (CM), and the extracellular vesicles (EVs), are also described in this review. This new approach has already shown promising results for bone tissue regeneration in experimental models.
... Stem cells present many advantages for use, since they have self-renewal capabilities and can easily be induced to differentiate into various lineages. 180,189,190 Although this broad categorization encompasses several different types, adult mesenchymal stem 33,35 Adult MSCs can be isolated from tissues such as bone marrow and adipose, which are vascularized. 30,180,183 They possess beneficial properties including multilineage potential for differentiation (adipogenic, chondrogenic, and osteogenic), high proliferative abilities, and immunomodulatory capabilities. ...
... 182 The cell number for isolation is dependent on various parameters including the donor's age and associated donor site morbidity and their limited quantity is a significant disadvantage to their use. 189 An alternative cell source for osteogenic applications includes adipose derived stem cells (ADSCs). These cells are attained from adipose tissue through minimally invasive surgical procedures such as liposuction. ...
... These cells are attained from adipose tissue through minimally invasive surgical procedures such as liposuction. 183,189,191 They can be retrieved in high abundance from harvesting, and their differentiation from fibroblast-like morphology makes them very interesting for rapid formation of connective tissue. 42,182,183,189,192,193 However, their osteogenic ability has been questioned since some studies have shown lower capability for differentiation compared to bone marrow derived stem cells. ...
An increasing number of publications over the past ten years have focused on the development of chitosan-based cross-linked scaffolds to regenerate bone tissue. The design of biomaterials for bone tissue engineering applications relies heavily on the ideals set forth by a polytherapy approach called the "Diamond Concept". This methodology takes into consideration the mechanical environment, scaffold properties, osteogenic and angiogenic potential of cells, and benefits of osteoinductive mediator encapsulation. The following review presents a comprehensive summarization of recent trends in chitosan-based cross-linked scaffold development within the scope of the Diamond Concept, particularly for nonload-bearing bone repair. A standardized methodology for material characterization, along with assessment of in vitro and in vivo potential for bone regeneration, is presented based on approaches in the literature, and future directions of the field are discussed.
... Because of the limited availability of biological bone substitutes, several tissue engineering strategies have been widely considered in the reconstruction of vascularized bone tissue and in the treatment of bone defects, namely, the combination of cells, biological molecules and/or (bio)materials [2]. Regarding the materials, they must be biocompatible and provide a suitable environment to accommodate a sufficient number of cells at the injury site and, therefore, promote cell adhesion, proliferation and differentiation without adverse effects on the host tissue [3]. It should preferably be biodegradable at a similar rate to that of bone formation, and the resulting by-products should be non-toxic (biosafety) [4,5]. ...
This study investigates the osteogenic differentiation of umbilical-cord-derived human mesenchymal stromal cells (hUC-MSCs) on biphasic calcium phosphate (BCP) scaffolds derived from cuttlefish bone doped with metal ions and coated with polymers. First, the in vitro cytocompatibility of the undoped and ion-doped (Sr2+, Mg2+ and/or Zn2+) BCP scaffolds was evaluated for 72 h using Live/Dead staining and viability assays. From these tests, the most promising composition was found to be the BCP scaffold doped with strontium (Sr2+), magnesium (Mg2+) and zinc (Zn2+) (BCP-6Sr2Mg2Zn). Then, samples from the BCP-6Sr2Mg2Zn were coated with poly(ԑ-caprolactone) (PCL) or poly(ester urea) (PEU). The results showed that hUC-MSCs can differentiate into osteoblasts, and hUC-MSCs seeded on the PEU-coated scaffolds proliferated well, adhered to the scaffold surfaces, and enhanced their differentiation capabilities without negative effects on cell proliferation under in vitro conditions. Overall, these results suggest that PEU-coated scaffolds are an alternative to PCL for use in bone regeneration, providing a suitable environment to maximally induce osteogenesis.
... These cells are usually originated from totally normal cells as described for all other cells. Surface biomarkers as CD13, CD44 and Ep CAM are specifically utilized with the objective to characterize these cancer cells from that of other cells of different types because they have ability to be expressed efficiently in normal tissues as well [33]. ...
... As previous reports have depicted that CD133 has been isolated well from brain, lungs, colorectal and gastric cancer and they exhibited the power of self-renewal and also the starting of tumor formation in body of organism [33]. The properties, which are identical to former in this scenario, include their evolution from normal cells along with the further biological characters. ...
Metastatic cancer cells cannot be removed from body using traditional methods such as surgery, radiotherapy and chemotherapy because the reoccurrence of disease is the common thing following treatment. But the therapies involving use of stem cells are proving to be a promising approach for treatment of cancer. They are the novel because they can provide homing to as well as targeting tumorous foci. Stem cells as a platform to deliver drugs to targets not only decrease volume of tumor but also enhance rate of survival in pre-clinical trials. They can also be employed as viral and other carriers in order to enhance the efficacy of drugs and providing enhanced permeability and retention after effects the same time with the least side effects. These stem cells can be applied in regenerative medicine, cancer cell therapy and immune cell-based therapy, and lastly for screening of anti-cancer drugs. Technically, treatment of cancer using stem cells is proved to be feasible but still there are certain challenges which need to be addressed such as durability of treatment and tumorigenesis. The recent chapter is focused on the stem cell review including its types, sources, applications, challenges and affectivity in terms of clinical trials which also aids in refining future.
... Rapidly developing bone tissue engineering has become an attractive approach to achieve the regeneration of defective bones [1,2]. Seed cells, scaffolds and growth factors, which are the main component elements of bone tissue engineering, have been widely studied and show beneficial effects on bone regeneration [3]. ...
Background
Periodontal ligament stem cells (PDLSCs) are important seed cells for tissue engineering to realize the regeneration of alveolar bone. Understanding the gene regulatory mechanisms of osteogenic lineage differentiation in PDLSCs will facilitate PDLSC-based bone regeneration. However, these regulatory molecular signals have not been clarified.
Methods
To screen potential regulators of osteogenic differentiation, the gene expression profiles of undifferentiated and osteodifferentiated PDLSCs were compared by microarray and bioinformatics methods, and PSAT1 was speculated to be involved in the gene regulation network of osteogenesis in PDLSCs. Lentiviral vectors were used to overexpress or knock down PSAT1 in PDLSCs, and then the proliferation activity, migration ability, and osteogenic differentiation ability of PDLSCs in vitro were analysed. A rat mandibular defect model was built to analyse the regulatory effects of PSAT1 on PDLSC-mediated bone regeneration in vivo. The regulation of PSAT1 on the Akt/GSK3β/β-catenin signalling axis was analysed using the Akt phosphorylation inhibitor Ly294002 or agonist SC79. The potential sites on the promoter of PSAT1 that could bind to the transcription factor ATF4 were predicted and verified.
Results
The microarray assay showed that the expression levels of 499 genes in PDLSCs were altered significantly after osteogenic induction. Among these genes, the transcription level of PSAT1 in osteodifferentiated PDLSCs was much lower than that in undifferentiated PDLSCs. Overexpressing PSAT1 not only enhanced the proliferation and osteogenic differentiation abilities of PDLSCs in vitro, but also promoted PDLSC-based alveolar bone regeneration in vivo, while knocking down PSAT1 had the opposite effects in PDLSCs. Mechanistic experiments suggested that PSAT1 regulated the osteogenic lineage fate of PDLSCs through the Akt/GSK3β/β-catenin signalling axis. PSAT1 expression in PDLSCs during osteogenic differentiation was controlled by transcription factor ATF4, which is realized by the combination of ATF4 and the PSAT1 promoter.
Conclusion
PSAT1 is a potential important regulator of the osteogenic lineage differentiation of PDLSCs through the ATF4/PSAT1/Akt/GSK3β/β-catenin signalling pathway. PSAT1 could be a candidate gene modification target for enhancing PDLSCs-based bone regeneration.
