Skeletal-related disorders such as arthritis, bone cancer, osteosarcoma, and osteoarthritis are among the most common reasons for mortality in humans at present. Nanostructured scaffolds have been discovered to be more efficient for bone regeneration than macro/micro-sized scaffolds because they sufficiently permit cell adhesion, proliferation, and chemical transformation. Nanofibrous scaffolds mimicking artificial extracellular matrices provide a natural environment for tissue regeneration owing to their large surface area, high porosity, and appreciable drug loading capacity. Here, we review recent progress and possible future prospective electrospun nanofibrous scaffolds for bone tissue engineering. Electrospun nanofibrous scaffolds have demonstrated promising potential in bone tissue regeneration using a variety of nanomaterials. This review focused on the crucial role of electrospun nanofibrous scaffolds in biological applications, including drug/growth factor delivery to bone tissue regeneration. Natural and synthetic polymeric nanofibrous scaffolds are extensively inspected to regenerate bone tissue. We focused mainly on the significant impact of nanofibrous composite scaffolds on cell adhesion and function, and different composites of organic/inorganic nanoparticles with nanofiber scaffolds. This analysis provides an overview of nanofibrous scaffold-based bone regeneration strategies; however, the same concepts can be applied to other organ and tissue regeneration tactics.

Diabetes mellitus is a chronic disease with a high mortality rate and many complications. A non-healing diabetic foot ulcer (DFU) is one the most serious complications, leading to lower-extremity amputation in 15% of diabetic patients. Nanofibers are emerging as versatile wound dressing due to their unique wound healing properties, such as a high surface area to volume ratio, porosity, and ability to maintain a moist wound environment capable of delivering sustained drug release and oxygen supply to a wound. The present study was aimed to prepare and evaluate a polyvinyl alcohol (PVA)–sodium alginate (SA)–silk fibroin (SF)-based multifunctional nanofibrous scaffold loaded with asiaticoside (AT) in diabetic rats. The SEM findings showed that fibers’ diameters ranged from 100–200 nm, and tensile strengths ranged from 12.41–16.80 MPa. The crosslinked nanofibers were sustained AT over an extended period. The MTT and scratch assay on HaCat cells confirmed low cytotoxicity and significant cell migration, respectively. Antimicrobial tests revealed an excellent anti-microbial efficacy against P. aeruginosa and S. aureus bacteria. In-vivo study demonstrated better wound healing efficacy in diabetic rats. In addition, the histopathological studies showed its ability to restore the normal structure of the skin. The present study concluded that developed multifunctional nanofibers have a great potential for diabetic wound healing applications.

Diabetic foot ulceration is the most distressing complication of diabetes having no standard therapy. Nanofibers are an emerging and versatile nanotechnology-based drug-delivery system with unique wound-healing properties. This study aimed to prepare and evaluate silk-sericin based hybrid nanofibrous mats for diabetic foot ulcer. The nanofibrous mats were prepared by electrospinning using silk sericin mixed with different proportions of polycaprolactone (PCL) and cellulose acetate (CA) loaded with ferulic acid (FA). The in vitro characterizations, such as surface morphology, mechanical properties, swelling behavior, biodegradability, scanning electron microscopy, and drug release were carried out. The SEM images indicated that nanofibers formed with varied diameters, ranging from 100 to 250 nm, and their tensile strength was found to range from 7 to 15 MPa. In vitro release demonstrated that the nanofibers sustained FA release over an extended time of period. In vitro cytotoxicity showed that the nanofibers possessed a lower cytotoxicity in HaCaT cells. The in vivo wound-healing studies demonstrated an excellent wound-healing efficiency of the nanofibers in diabetic rats. Furthermore, the histopathological studies showed the nanofibers’ ability to restore the skin’s normal structure. Therefore, it was concluded that the prepared silk-sericin-based hybrid nanofibers loaded with FA could be a promising drug-delivery platform for the effective treatment of diabetic foot ulcers.

The advent of pH-sensitive liposomes (pHLips) has opened new opportunities for the improved and targeted delivery of antitumor drugs as well as gene therapeutics. Comprising fusogenic dioleylphosphatidylethanolamine (DOPE) and cholesteryl hemisuccinate (CHEMS), these nanosystems harness the acidification in the tumor microenvironment and endosomes to deliver drugs effectively. pH-responsive liposomes that are internalized through endocytosis encounter mildly acidic pH in the endosomes and thereafter fuse or destabilize the endosomal membrane, leading to subsequent cargo release into the cytoplasm. The extracellular tumor matrix also presents a slightly acidic environment that can lead to the enhanced drug release and improved targeting capabilities of the nano-delivery system. Recent studies have shown that folic acid (FA) and iRGD-coated nanocarriers, including pH-sensitive liposomes, can preferentially accumulate and deliver drugs to breast tumors that overexpress folate receptors and αvβ3 and αvβ5 integrins. This study focuses on the development and characterization of 5-Fluorouracil (5-FU)-loaded FA and iRGD surface-modified pHLips (FA-iRGD-5-FU-pHLips). The novelty of this research lies in the dual targeting mechanism utilizing FA and iRGD peptides, combined with the pH-sensitive properties of the liposomes, to enhance selective targeting and uptake by cancer cells and effective drug release in the acidic tumor environment. The prepared liposomes were small, with an average diameter of 152 ± 3.27 nm, uniform, and unilamellar, demonstrating efficient 5-FU encapsulation (93.1 ± 2.58%). Despite surface functionalization, the liposomes maintained their pH sensitivity and a neutral zeta potential, which also conferred stability and reduced aggregation. Effective pH responsiveness was demonstrated by the observation of enhanced drug release at pH 5.5 compared to physiological pH 7.4. (84.47% versus 46.41% release at pH 5.5 versus pH 7.4, respectively, in 72 h). The formulations exhibited stability for six months and were stable when subjected to simulated biological settings. Blood compatibility and cytotoxicity studies on MDA-MB-231 and SK-BR3 breast cancer cell lines revealed an enhanced cytotoxicity of the liposomal formulation that was modified with FA and iRGD compared to free 5-FU and minimal hemolysis. Collectively, these findings support the potential of FA and iRGD surface-camouflaged, pH-sensitive liposomes as a promising drug delivery strategy for breast cancer treatment.

Osteogenic-osteoclast coupling processes play a crucial role in bone regeneration. Recently, strategies that focus on multi-functionalized implant surfaces to enhance the healing of bone defects through the synergistic regulation of osteogenesis and osteoclastogenesis is still a challenging task in the field of bone tissue engineering. The aim of this study was to create a dual-drug release-based core-shell nanofibers with the intent of achieving a time-controlled release to facilitate bone regeneration. We fabricated core-shell P/PCL nanofibers using coaxial electrospinning, where alendronate (ALN) was incorporated into the core layer and hydroxyapatite (HA) into shell. The surface of the nanofiber construct was further modified with mussel-derived polydopamine (PDA) to induce hydrophilicity and enhance cell interactions. Surface characterizations confirmed the successful synthesis of PDA@PHA/PCL-ALN nanofibers endowed with excellent mechanical strength (20.02 ± 0.13 MPa) and hydrophilicity (22.56°), as well as the sustained sequential release of ALN and Ca ions. In vitro experiments demonstrated that PDA-functionalized core-shell PHA/PCL-ALN scaffolds possessed excellent cytocompatibility, enhanced cell adhesion and proliferation, alkaline phosphatase activity and osteogenesis-related genes. In addition to osteogenesis, the engineered scaffolds also significantly reduced osteoclastogenesis, such as tartrate-resistant acid phosphatase activity and osteoclastogenesis-related gene expression. After 12-week of implantation, it was observed that PDA@PHA/PCL-ALN nanofiber scaffolds, in a rat cranial defect model, significantly promoted bone repair and regeneration. Microcomputed tomography, histological examination, and immunohistochemical analysis collectively demonstrated that the PDA-functionalized core-shell PHA/PCL-ALN scaffolds exhibited exceptional osteogenesis-inducing and osteoclastogenesis-inhibiting effects. Finally, it may be concluded from our results that the bio-inspired surface-functionalized multifunctional, biomimetic and controlled release core-shell nanofiber provides a promising strategy to facilitate bone healing.

Human epidermal growth factor receptor-2 (HER2)-positive breast cancer metastasis remains the primary cause of mortality among women globally. Targeted therapies have revolutionized treatment efficacy, with Trastuzumab (Trast), a monoclonal antibody, targeting HER2-positive advanced breast cancer. The tumor-homing peptide iRGD enhances the intratumoral accumulation and penetration of therapeutic agents. Liposomes serve as versatile nanocarriers for both hydrophilic and hydrophobic drugs. Gefitinib (GFB) is a potential anticancer drug against HER2-positive breast cancer, while Lycorine hydrochloride (LCH) is a natural compound with anticancer and anti-inflammatory properties. This study developed TPGS-COOH-coated liposomes co-loaded with GFB and LCH, prepared by the solvent injection method, and surface-functionalized with Trast and iRGD. The dual surface-decorated liposomes (DSDLs) were characterized for their particle size (PS), polydispersity index (PDI), zeta potential (ZP), surface chemistry, surface morphology, and their crystallinity during in-vitro drug release, drug encapsulation, and in-vitro cell line studies on SK-BR-3 and MDA-MB-231 breast cancer cells. The half-maximum inhibitory concentration (IC-50) values of single decorated liposomes (SDLs), iRGD-LP, and Trast-LP, as well as DSDLs (iRGD-Trast-LP) on SK-BR-3 cells, were 6.10 ± 0.42, 4.98 ± 0.36, and 4.34 ± 0.32 μg/mL, respectively. Moreover, the IC-50 values of SDLs and DSDLs on MDA-MB-231 cells were 15.12 ± 0.68, 13.09 ± 0.59, and 11.08 ± 0.48 μg/mL, respectively. Cellular uptake studies using confocal laser scanning microscopy (CLSM) showed that iRGD and Trast functionalization significantly enhanced cellular uptake in both cell lines. The wound-healing assay demonstrated a significant reduction in SDL and DSDL-treated MDA-MB-231 cell migration compared to the control. Additionally, the blood compatibility study showed minimal hemolysis (less than 5% RBC lysis), indicating good biocompatibility and biosafety. Overall, these findings suggest that TPGS-COOH-coated, GFB and LCH co-loaded, dual-ligand (iRGD and Trast) functionalized, multifunctional liposomes could be a promising therapeutic strategy for treating HER2-positive metastatic breast cancer.