Search Results (13)

Background: Osteoporosis has become an inevitable health issue with global aging, and the current drug treatments often have adverse side effects, highlighting the need for safer and more effective therapies. Collagen-derived peptides are promising alternatives due to their favorable safety profile and biological activity. This study aimed to investigate the osteogenic and anti-apoptotic properties of collagen peptide UU1 (GASGPMGPR) in addition to its antioxidant activity. Methods: The effects of UU1 were evaluated in MC3T3-E1 cells by assessing osteogenic markers, including alkaline phosphatase (ALP), Cyclin D1, runt-related transcription factor 2 (Runx2), and Akt/β-catenin signaling. Western blot analysis quantified collagen I, osteocalcin, and phosphorylated Akt levels. Anti-apoptotic effects were measured via p-Akt levels and the Bax/Bcl-2 ratio. Computational molecular docking was performed to explore the molecular mechanism of UU1 via its interaction with epidermal growth factor receptor (EGFR) and collagen-binding integrin. Results: UU1 treatment promoted cell differentiation, with elevated ALP, Cyclin D1, Runx2, and Akt/β-catenin signaling. Notably, at 0.025 mg/mL, UU1 upregulated the levels of collagen I, osteocalcin, and phosphorylated Akt by 2.14, 3.37, and 1.95 times, respectively, compared to the control. Additionally, UU1 exhibited anti-apoptotic effects, indicated by increased p-Akt levels and a reduced Bax/Bcl-2 ratio. Molecular docking analysis suggested that UU1 could assist the dimerization of EGFR, facilitating downstream signaling transductions and activating collagen-binding integrin. Conclusions: These findings highlight UU1 as a multifunctional peptide with antioxidant, osteogenic, and anti-apoptotic properties, positioning it as a promising candidate for anti-osteoporosis applications in the food and pharmaceutical industries. Full article

Bone has the ability to heal itself; however, bone defects fail to heal once the damage exceeds a critical size. Bone regeneration remains a significant clinical challenge, with autograft considered the ideal bone graft material due to its sufficient porosity, osteogenic cells, and biological growth factors. However, limitations to bone grafting, such as limited bone stock and high resorption rates, have led to a great deal of research into developing bone graft substitutes. The P28 peptide is a small molecule bioactive biomimetic alternative to mimic the bone morphogenetic protein 2 (BMP-2). In this study, we investigated the potential of P28-loaded hybrid scaffolds to mimic the natural bone structure for enhancing the bone regeneration process. We hypothesized that the peptide-loaded scaffolds and nude scaffolds both have the potential to promote bone healing, and the bone healing process is accelerated by the release of the peptide. To verify our hypothesis, C2C12 cells were evaluated for the presence of calcium deposits by histological stain at 7 and 14 days in cultures with hybrid scaffolds. Total RNA was isolated from C2C12 cells cultured with hybrid scaffolds for 7 and 14 days to assess osteoblast differentiation. The project findings demonstrated that the hybrid scaffold could enhance osteoblast differentiation and significantly improve the therapeutic effects of the scaffold in bone regeneration. Full article

The regeneration of periodontal bone defects continues to be an essential therapeutic concern in dental biomaterials. Numerous biomaterials have been utilized in this sector so far. However, the immune response and vascularity in defect regions may be disregarded when evaluating the effectiveness of biomaterials for bone repair. Among several regenerative treatments, the most recent technique of in situ tissue engineering stands out for its ability to replicate endogenous restorative processes by combining scaffold with particular growth factors. Regenerative medicine solutions that combine biomaterials/scaffolds, cells, and bioactive substances have attracted significant interest, particularly for bone repair and regeneration. Dental stem cells (DSCs) share the same progenitor and immunomodulatory properties as other types of MSCs, and because they are easily isolable, they are regarded as desirable therapeutic agents in regenerative dentistry. Recent research has demonstrated that DSCs sown on newly designed synthetic bio-material scaffolds preserve their proliferative capacity while exhibiting increased differentiation and immuno-suppressive capabilities. As researchers discovered how short peptide sequences modify the adhesion and proliferative capacities of scaffolds by activating or inhibiting conventional osteogenic pathways, the scaffolds became more effective at priming MSCs. In this review, the many components of tissue engineering applied to bone engineering will be examined, and the impact of biomaterials on periodontal regeneration and bone cellular biology/molecular genetics will be addressed and updated. Full article

Articular cartilage is characterized by a poor self-healing capacity due to its aneural and avascular nature. Once injured, it undergoes a series of catabolic processes which lead to its progressive degeneration and the onset of a severe chronic disease called osteoarthritis (OA). In OA, important alterations of the morpho-functional organization occur in the cartilage extracellular matrix, involving all the nearby tissues, including the subchondral bone. Osteochondral engineering, based on a perfect combination of cells, biomaterials and biomolecules, is becoming increasingly successful for the regeneration of injured cartilage and underlying subchondral bone tissue. To this end, recently, several peptides have been explored as active molecules and enrichment motifs for the functionalization of biomaterials due to their ability to be easily chemically synthesized, as well as their tunable physico-chemical features, low immunogenicity issues and functional group modeling properties. In addition, they have shown a good aptitude to penetrate into the tissue due to their small size and stability at room temperature. In particular, growth-factor-derived peptides can play multiple functions in bone and cartilage repair, exhibiting chondrogenic/osteogenic differentiation properties. Among the most studied peptides, great attention has been paid to transforming growth factor-β and bone morphogenetic protein mimetic peptides, cell-penetrating peptides, cell-binding peptides, self-assembling peptides and extracellular matrix-derived peptides. Moreover, recently, phage display technology is emerging as a powerful selection technique for obtaining functional peptides on a large scale and at a low cost. In particular, these peptides have demonstrated advantages such as high biocompatibility; the ability to be immobilized directly on chondro- and osteoinductive nanomaterials; and improving the cell attachment, differentiation, development and regeneration of osteochondral tissue. In this context, the aim of the present review was to go through the recent literature underlining the importance of studying novel functional motifs related to growth factor mimetic peptides that could be a useful tool in osteochondral repair strategies. Moreover, the review summarizes the current knowledge of the use of phage display peptides in osteochondral tissue regeneration. Full article

Mg–Zn–Ca bulk metallic glass (BMG) is a promising orthopedic fixation implant because of its biodegradable and biocompatible properties. Structural supporting bone implants with osteoinduction properties for effective bone regeneration have been highly desired in recent years. Osteogenic growth peptide (OGP) can increase the proliferation and differentiation of mesenchymal stem cells and enhance the mineralization of osteoblast cells. However, the short half-life and non-specificity to target areas limit applications of OGP. Mesoporous silica nanoparticles (MSNs) as nanocarriers possess excellent properties, such as easy surface modification, superior targeting efficiency, and high loading capacity of drugs or proteins. Accordingly, we propose a system of combining the OGP-containing MSNs with Mg–Zn–Ca BMG materials to promote bone regeneration. In this work, we conjugated cysteine-containing OGP (cgOGP, 16 a.a.) to interior walls of channels in MSNs and maintained the dispersity of MSNs via PEGylation. An in vitro study showed that metal ions released from Mg–Zn–Ca BMG promoted cell proliferation and migration and elevated alkaline phosphatase (ALP) activity and mineralization. On treating cells with both BMG ion-containing Minimum Essential Medium Eagle-alpha modification (α-MEM) and OGP-conjugated MSNs, enhanced focal adhesion turnover and promoted differentiation were observed. Hematological analyses showed the biocompatible nature of this BMG/nanocomposite system. In addition, in vivo micro-computed tomographic and histological observations revealed that our system stimulated osteogenesis and new bone formation around the implant site. Full article

Graphene oxide (GO) is extensively studied as a template material for mesenchymal stem cell application due to its two-dimensional nature and unique functionalization chemistries. Herein, a new type of peptide-conjugated multilayer graphene oxide (peptide/m-GO film) was fabricated and used as biomaterial for culturing human Wharton’s jelly-derived mesenchymal stem cells (WJ-MSCs). The characterization of the peptide/m-GO films was performed, and the biocompatibility of the WJ-MSCs on the peptide/m-GO films was investigated. The results demonstrated that the peptide conjugate on the m-GO film did not hamper the normal growth of WJ-MSCs but supported the growth of WJ-MSCs after the 6-day culture period. In addition, the osteogenic differentiation of WJ-MSCs on the peptide/m-GO films was enhanced as compared with the parent m-GO film. Therefore, such peptide-conjugated m-GO films could provide a highly biocompatible and multifunctional 2D material to tailor the potential application of WJ-MSCs in bone tissue regeneration. Full article

Scaffolds stimulate cell proliferation and differentiation and play major roles in providing growth and nutrition factors in the repair of bone defects. We used the recombinant peptide Cellnest™ to prepare the three-dimensional stem cell complex, CellSaic, and evaluated whether CellSaic containing rat dental pulp stem cells (rDPSCs) was better than that containing rat bone marrow stem cells (rBMSCs). rDPSC-CellSaic or rBMSC-CellSaic, cultured with or without osteogenic induction medium, formed the experimental and control groups, respectively. Osteoblast differentiation was evaluated in vitro and transplanted into a rat model with a congenital jaw fracture. Specimens were collected and evaluated by microradiology and histological analysis. In the experimental group, the amount of calcium deposits, expression levels of bone-related genes (RUNX2, ALP, BSP, and COL1), and volume of mineralized tissue, were significantly higher than those in the control group (p < 0.05). Both differentiated and undifferentiated rDPSC-CellSaic and only the differentiated rBMSC-CellSaic could induce the formation of new bone tissue. Overall, rBMSC-CellSaic and rDPSC-CellSaic made with Cellnest™ as a scaffold, provide excellent support for promoting bone regeneration in rat mandibular congenital defects. Additionally, rDPSC-CellSaic seems a better source for craniofacial bone defect repair than rBMSC-CellSaic, suggesting the possibility of using DPSCs in bone tissue regenerative therapy. Full article

Human erythropoietin (EPO) is an N-linked glycoprotein consisting of 166 aa that is produced in the kidney during the adult life and acts both as a peptide hormone and hematopoietic growth factor (HGF), stimulating bone marrow erythropoiesis. EPO production is activated by hypoxia and is regulated via an oxygen-sensitive feedback loop. EPO acts via its homodimeric erythropoietin receptor (EPO-R) that increases cell survival and drives the terminal erythroid maturation of progenitors BFU-Es and CFU-Es to billions of mature RBCs. This pathway involves the activation of multiple erythroid transcription factors, such as GATA1, FOG1, TAL-1, EKLF and BCL11A, and leads to the overexpression of genes encoding enzymes involved in heme biosynthesis and the production of hemoglobin. The detection of a heterodimeric complex of EPO-R (consisting of one EPO-R chain and the CSF2RB β-chain, CD131) in several tissues (brain, heart, skeletal muscle) explains the EPO pleotropic action as a protection factor for several cells, including the multipotent MSCs as well as cells modulating the innate and adaptive immunity arms. EPO induces the osteogenic and endothelial transdifferentiation of the multipotent MSCs via the activation of EPO-R signaling pathways, leading to bone remodeling, induction of angiogenesis and secretion of a large number of trophic factors (secretome). These diversely unique properties of EPO, taken together with its clinical use to treat anemias associated with chronic renal failure and other blood disorders, make it a valuable biologic agent in regenerative medicine for the treatment/cure of tissue de-regeneration disorders. Full article

In the last twenty years, due to an increasing medical and market demand for orthopaedic implants, several grafting options have been developed. However, when alternative bone augmentation materials mimicking autografts are searched on the market, commercially available products may be grouped into three main categories: cellular bone matrices, growth factor enhanced bone grafts, and peptide enhanced xeno-hybrid bone grafts. Firstly, to obtain data for this review, the search engines Google and Bing were employed to acquire information from reports or website portfolios of important competitors in the global bone graft market. Secondly, bibliographic databases such as Medline/PubMed, Web of Science, and Scopus were also employed to analyse data from preclinical/clinical studies performed to evaluate the safety and efficacy of each product released on the market. Here, we discuss several products in terms of osteogenic/osteoinductive/osteoconductive properties, safety, efficacy, and side effects, as well as regulatory issues and costs. Although both positive and negative results were reported in clinical applications for each class of products, to date, peptide enhanced xeno-hybrid bone grafts may represent the best choice in terms of risk/benefit ratio. Nevertheless, more prospective and controlled studies are needed before approval for routine clinical use. Full article

The most common bone disease in humans is osteoporosis (OP). Current therapeutics targeting OP have several negative side effects. Bone morphogenetic protein 2 (BMP2) is a potent growth factor that is known to activate both osteoblasts and osteoclasts. It completes these actions through both SMAD-dependent and SMAD-independent signaling. A novel interaction between the BMP type Ia receptor (BMPRIa) and casein kinase II (CK2) was discovered, and several CK2 phosphorylation sites were identified. A corresponding blocking peptide (named CK2.3) was designed to further elucidate the phosphorylation site’s function. Previously, CK2.3 demonstrated an increased osteoblast activity and decreased osteoclast activity in a variety of animal models, cell lines, and isolated human osteoblasts. It is hypothesized that CK2.3 completes these actions through the BMP signaling pathway. Furthermore, it was recently discovered that BMP2 did not elicit an osteogenic response in osteoblasts from patients diagnosed with OP, while CK2.3 did. In this study, we explore where in the BMP pathway the signaling disparity or defect lies in those diagnosed with OP. We found that osteoblasts isolated from patients diagnosed with OP did not activate SMAD or ERK signaling after BMP2 stimulation. When OP osteoblasts were stimulated with BMP2, both BMPRIa and CK2 expression significantly decreased. This indicates a major disparity within the BMP signaling pathway in patients diagnosed with osteoporosis. Full article

Spinal fusion is the most widely performed procedure in spine surgery. It is the preferred treatment for a wide variety of pathologies including degenerative disc disease, spondylolisthesis, segmental instability, and deformity. Surgeons have the choice of fusing vertebrae by utilizing cages containing autografts, allografts, demineralized bone matrices (DBMs), or graft substitutes such as ceramic scaffolds. Autografts from the iliac spine are the most commonly used as they offer osteogenic, osteoinductive, and osteoconductive capabilities, all while avoiding immune system rejection. Allografts obtained from cadavers and living donors can also be advantageous as they lack the need for graft extraction from the patient. DBMs are acid-extracted organic allografts with osteoinductive properties. Ceramic grafts containing hydroxyapatite can be readily manufactured and are able to provide osteoinductive support while having a long shelf life. Further, bone-morphogenetic proteins (BMPs), mesenchymal stem cells (MSCs), synthetic peptides, and autologous growth factors are currently being optimized to assist in improving vertebral fusion. Genetic therapies utilizing viral transduction are also currently being devised. This review provides an overview of the advantages, disadvantages, and future directions of currently available graft materials. The current literature on growth factors, stem cells, and genetic therapy is also discussed. Full article

Mesoporous Bioactive Glasses (MBGs) are a family of bioceramics widely investigated for their putative clinical use as scaffolds for bone regeneration. Their outstanding textural properties allow for high bioactivity when compared with other bioactive materials. Moreover, their great pore volumes allow these glasses to be loaded with a wide range of biomolecules to stimulate new bone formation. In this study, an MBG with a composition, in mol%, of 80% SiO₂–15% CaO–5% P₂O₅ (Blank, BL) was compared with two analogous glasses containing 4% and 5% of ZnO (4ZN and 5ZN) before and after impregnation with osteostatin, a C-terminal peptide from a parathyroid hormone-related protein (PTHrP_107-111). Zn²⁺ ions were included in the glass for their bone growth stimulator properties, whereas osteostatin was added for its osteogenic properties. Glasses were characterized, and their cytocompatibility investigated, in pre-osteoblastic MC3T3-E1 cell cultures. The simultaneous additions of osteostatin and Zn²⁺ ions provoked enhanced MC3T3-E1 cell viability and a higher differentiation capacity, compared with either raw BL or MBGs supplemented only with osteostatin or Zn²⁺. These in vitro results show that osteostatin enhances the osteogenic effect of Zn²⁺-enriched glasses, suggesting the potential of this combined approach in bone tissue engineering applications. Full article

Bone regeneration is a process that involves several molecular mediators, such as growth factors, which directly affect the proliferation, migration and differentiation of bone-related cells. The osteogenic growth peptide (OGP) and its C-terminal pentapeptide OGP(10–14) have been shown to stimulate the proliferation, differentiation, alkaline phosphatase activity and matrix mineralization of osteoblastic lineage cells. However, the exact molecular mechanisms that promote osteoblastic proliferation and differentiation are not completely understood. This review presents the main chemical characteristics of OGP and/or OGP(10–14), and also discusses the potential molecular pathways induced by these growth factors to promote proliferation and differentiation of osteoblasts. Furthermore, since these peptides have been extensively investigated for bone tissue engineering, the clinical applications of these peptides for bone regeneration are discussed. Full article