Bioactive Molecule-incorporated Polymeric Electrospun Fibers for Bone Tissue Engineering.

Bone tissue engineering (BTE) is based on the participation and combination of different biomaterials, cells, and bioactive molecules to generate biosynthetic grafts for bone regeneration. Electrospinning has been used to fabricate fibrous scaffolds, which provide nanoscale architecture comprising interconnecting pores, resembling the natural hierarchy of tissues and enabling the formation of artificial functional tissues. Electrospun fibers for BTE applications have been mostly produced from polymers (chitosan, alginate, polycaprolactone, polylactic acid) and bioceramics (hydroxyapatite). Stem cells are among the most prolific cell types employed in regenerative medicine owing to their self-renewal and differentiation capacity. Most importantly, bioactive molecules, such as synthetic drugs, growth factors, and phytocompounds, are consistently used to regulate cell behavior inducing differentiation towards the osteoblast lineage. An expanding body of literature has provided evidence that these electrospun fibers loaded with bioactive molecules support the differentiation of stem cells towards osteoblasts. Thus, this review briefly describes the current development of polymers and bioceramic-based electrospun fibers and the influence of bioactive molecules in these electrospun fibers on bone tissue regeneration.

Angiogenic and osteogenic effects of flavonoids in bone regeneration.

Bone is a highly vascularized tissue that relies on a close spatial and temporal interaction between blood vessels and bone cells. As a result, angiogenesis is critical for bone formation and healing. The vascular system supports bone regeneration by delivering oxygen, nutrients, and growth factors, as well as facilitating efficient cell-cell contact. Most clinical applications of engineered bone grafts are hampered by insufficient vascularization after implantation. Over the last decade, a number of flavonoids have been reported to have osteogenic-angiogenic potential in bone regeneration because of their excellent bioactivity, low cost, availability, and minimal in vivo toxicity. During new bone formation, the osteoinductive nature of certain flavonoids is involved in regulating multiple signaling pathways contributing toward the osteogenic-angiogenic coupling. This review briefly outlines the osteogenic-angiogenic potential of those flavonoids and the mechanisms of their action in promoting bone regeneration. However, further studies are needed to investigate their delivery strategies and establish their clinical efficacy.

Advancements in nucleic acids-based techniques for bone regeneration.

The dynamic biology of bone involving an enormous magnitude of cellular interactions and signaling transduction provides ample biomolecular targets, which can be enhanced or repressed to mediate a rapid regeneration of the impaired bone tissue. The delivery of nucleic acids such as DNA and RNA can enhance the expression of osteogenic proteins. Members of the RNA interference pathway such as miRNA and siRNA can repress negative osteoblast differentiation regulators. Advances in nanomaterials have provided researchers with a plethora of delivery modules that can ensure proper transfection. Combining the nucleic acid carrying vectors with bone scaffolds has met with tremendous success in accomplishing bone formation. Recent years have witnessed the advent of CRISPR and DNA nanostructures in regenerative medicine. This review focuses on the delivery of nucleic acids and touches upon the prospect of CRISPR and DNA nanostructures for bone tissue engineering, emphasizing their potential in treating bone defects.

Three-dimensional-poly(lactic acid) scaffolds coated with gelatin/magnesium-doped nano-hydroxyapatite for bone tissue engineering.

BACKGROUND: Treatment of critical-sized bone defects has progressively evolved over the years from metallic implants to more ingenious three-dimensional-based scaffolds. The use of three-dimensional scaffolds for bone regeneration from biodegradable polymers like poly(lactic acid) (PLA) is gaining popularity. Scaffolds with surface functionalization using gelatin (Gel) have the advantages of biocompatibility and cell adhesion. Nano-hydroxyapatite (nHAp) is one of the most promising implant materials utilized in orthopaedics. The osteogenic potential of the nHAp can be improved by the substitution of magnesium (Mg) ions onto the crystal lattice of nHAp. Thus, the goal of this work was to make three-dimensional-PLA scaffolds covered with Gel/Mg-nHAp for osteogenic effect. METHODS AND RESULTS: The designed three-dimensional-PLA/Gel/Mg-nHAp scaffolds were attributed to various characterizations for the examination of their physicochemical, mechanical properties, cyto-compatibility, and biodegradability as well as their ability to promote osteogenesis in vitro. Mouse mesenchymal stem cells (mMSCs) were cytocompatible with these scaffolds. The osteogenic potential of three-dimensional-PLA/Gel/Mg-nHAp scaffolds employing mMSCs was validated at the cellular and molecular levels. The three-dimensional-PLA/Gel/Mg-nHAp scaffolds stimulated the differentiation of mMSCs towards osteoblastic lineage. CONCLUSION: Based on these findings, we suggest that the three-dimensional-PLA/Gel/Mg-nHAp scaffolds' osteogenic capability may be advantageous in the mending of bone defects in orthopedic applications.

Osteogenic potential of zingerone, a phenolic compound in mouse mesenchymal stem cells.

Zingerone, 4-(4-hydroxy-3-methoxyphenyl)-2-butanone (Zg), a phenolic compound isolated from ginger is reported to have anti-inflammatory and antidiabetic properties. However, its role in the promotion of osteogenesis is not known. In this study, we investigated the therapeutic effect of Zg on osteogenesis at the cellular and molecular levels. Zg treatment was nontoxic to mouse mesenchymal stem cells (mMSCs). At the cellular level, it enhanced osteoblast differentiation as evidenced by more calcium deposits. At the molecular level, Zg stimulated the expression of Runx2 (a bone transcription factor) and other marker genes of osteoblast differentiation in mMSCs. Recent studies indicated that microRNAs (miRNAs) regulate bone metabolism, and we identified that Zg treatment in mMSCs upregulated mir-590, a positive regulator of Runx2 by targeting Smad7, an antagonist of TGF-ß1 signaling. Thus, the osteogenic potential of Zg would be beneficial for treating bone and bone-related diseases.

Sinapic acid-loaded chitosan nanoparticles in polycaprolactone electrospun fibers for bone regeneration in vitro and in vivo.

Sinapic acid (SA) is a plant-derived phenolic compound known for its multiple biological properties, but its role in the promotion of bone formation is not yet well-studied. Moreover, the delivery of SA is hindered by its complex hydrophobic nature, limiting its bioavailability. In this study, we fabricated a drug delivery system using chitosan nanoparticles (nCS) loaded with SA at different concentrations. These were incorporated into polycaprolactone (PCL) fibers via an electrospinning method. nCS loaded with 50 µM SA in PCL fibers promoted osteoblast differentiation. Furthermore, SA treatment activated the osteogenesis signaling pathways in mouse mesenchymal stem cells. A critical-sized rat calvarial bone defect model system identified that the inclusion of SA into PCL/nCS fibers accelerated bone formation. Collectively, these data suggest that SA promoted osteoblast differentiation in vitro and bone formation in vivo, possibly by activating the TGF-ß1/BMP/Smads/Runx2 signaling pathways, suggesting SA might have therapeutic benefits in bone regeneration.

Chitosan and gelatin-based electrospun fibers for bone tissue engineering.

Fractures and injuries pertaining to bone tissue usually take prolonged periods for its natural healing. To overcome this problem, the field of bone tissue engineering (BTE) has acquired an efficient designing mechanism that incorporates cells, biomaterials and the corresponding growth factors to promote both osteogenesis as well as mineralization of the bone. Amidst the various techniques available for scaffold creation, electrospinning is considered superior as it paves the way for the creation of nanostructured scaffolds using biopolymers. Chitosan (CS) and Gelatin (Gel) are two of the cardinal natural biopolymers used in the field of biomaterials and tissue engineering. They can be used either exclusively or in combination with other biopolymers for the enhancement of bone regeneration. Hence, this review aims to render an elaborate study on the CS and Gel-based nanofibrous scaffolds with and without additional composites and the properties that they portray in terms of BTE.