Delivery Of bFGF Research Articles

Liposomal nano-encapsulation of bFGF combined with injectable BSA hydrogel for efficient burn wound healing

Rapid and scar-free healing of burn wounds is an urgent clinical issue. Basic fibroblast growth factor (bFGF) has been proven to promote the healing of burn wounds by accelerating ECM remodeling and angiogenesis. However, exudates from burn wounds can accelerate bFGF degradation, thereby affecting its bioactivity. This study proposes an effective protection strategy for bFGF that involves encapsulating bFGF in nanoliposomes (bFGF-NLip) and then incorporating bFGF-NLip into a bovine serum albumin (BSA) hydrogel. This hybrid hydrogel system (bFGF-NLip@B) could maintain the activity of bFGF, achieve sustained release, and allow phospholipids and cholesterol to penetrate the skin, thereby enabling bFGF to function in the dermis. The experimental results showed that the hydrogel was injectable with good mechanical properties and biocompatibility. In a mouse scald wound model, owing to the sustained release of bFGF and skin permeation function of the nanoliposomes, the hydrogel promoted granulation formation, collagen deposition, vascular regeneration, and re-epithelialisation, ultimately accelerating wound healing. In addition, the hydrogel effectively inhibited scar formation. This system provides novel insights into the delivery of bFGF and scar-free healing of burn wounds.

Accelerating healing at high altitudes: Oxygen and bFGF delivery through nanoparticle-loaded gel dressings

High altitude environment is mainly characterized by low oxygen. Due to persistent hypoxia, nonhealing wounds are common in high-altitude areas. Moreover, Basic fibroblast growth factor (bFGF) is a versatile biologically active substance that has crucial impact on wound healing. Given the limited availability of atmospheric oxygen and reduced blood oxygen saturation in high-altitude area, and the challenge that arises from direct oxygen and bFGF delivery to wounds through the traumatized vascular structure, it necessitates an innovative solution for local and permeable delivery of oxygen and bFGF. In this study, we present a strategy that involves revamping traditional gel-based wound dressings through the incorporation of nanoparticles encapsulating oxygen and bFGF, engineered to facilitate the localized delivery of dissolved oxygen and bFGF to wound surfaces. The prospective evaluation of this delivery technique's therapeutic impacts on epithelial, endothelial and fibroblasts cells can be materialized. Further experiment corroborated these effects on a high-altitude wounds' murine model. Given its biocompatibility, efficacy, and utility, we posit that NOB-Gel exhibits remarkable translational potential for managing and hastening the healing process of an array of clinical wounds, more so for wounds inflicted at high altitudes.

Biomimetic nanoparticles of platelet membranes carrying bFGF and VEGFA genes promote deep burn wound healing

IntroductionThe treatment of burn wounds, especially deep burn wounds, remains a major clinical challenge. Growth factors such as basic fibroblast growth factor (bFGF) and vascular endothelial growth factor A (VEGFA) show great potential in promoting the healing of damaged tissues. This study explored wound healing following targeted delivery of bFGF and VEGFA genes into deep burn wounds through a novel platelet membrane-coated nanoparticle (PM@gene-NP) complex delivery system. MethodsFirst, bFGF and VEGFA genes were inserted into plasmid (pEGFP-N1) vectors. Subsequently, the assembled plasmids were loaded onto nanoparticles to form gene-loaded nanoparticle complexes, which were then wrapped with extracted platelet membrane, fully simulating the characteristics of platelets, in order to actively target sites of inflammatory damage. After administration of PM@gene-NP complexes through the tail vein of rats, a series of experiments were conducted to evaluate wound healing. ResultsThe PM@gene-NP complexes effectively targeted the burn sites. After the administration of the PM@gene-NP complexes, the rats exhibited increased blood flow in the burn wounds, which also healed faster than control groups. Histological results showed fewer inflammatory cells in the burned skin tissue after treatment. After the wounds healed, the production of hair follicles, sebaceous glands and other skin accessories in the skin tissue increased. ConclusionOur results showed that the PM@gene-NP complexes can effectively deliver gene therapy to the injured area, and this delivery system should be considered as a potential method for treating deep burns.

Subcutaneous angiogenesis induced by transdermal delivery of gel-in-oil nanogel dispersion

Subcutaneous transplantation aims to enhance the growth and functionality of transplanted cells for therapeutic outcomes in tissue engineering. However, the limited subcutaneous vascular network poses a challenge. Conventional methods involve co-transplantation with endothelial cells or angiogenic scaffold implantation, but they have drawbacks like tissue inflammation, compromised endothelial cell functionality, and the risk of repeated scaffold transplantation. Effective techniques are needed to overcome these challenges. This study explores the potential of G/O-NGD, a gel-in-oil nanogel dispersion, as a transdermal carrier of proliferative factors to promote angiogenesis in subcutaneous graft beds before cell transplantation. We observed robust subcutaneous angiogenesis by delivering varying amounts of bFGF using the G/O-NGD emulsion. Quantitative analysis of several parameters confirmed the efficacy of this method for building a subcutaneous vascular network. G/O-NGD is a biodegradable material that facilitates localized transdermal delivery of bFGF while maintaining its activity. The findings of this study have significant implications in both medical and industrial fields.

Biomaterial-Based bFGF Delivery for Nerve Repair.

Diseases in the nervous system are common in the human body. People have to suffer a great burden due to huge economic costs and poor prognosis of the diseases. Many treatment modalities are now available that can make recovery better. Managing nutritional factors is also helpful for such diseases. The basic fibroblast growth factor (bFGF) is one of the major nutritional factors, which plays a crucial role in organogenesis and tissue homeostasis. It plays a role in cell proliferation, migration, and differentiation, thereby regulating angiogenesis and wound healing and repair of the muscle, bone, and nerve. The study on how to improve the stability of bFGF to increase the treatment effect for different diseases has garnered tremendous attention. Biomaterials are the popular methods to improve the stability of bFGF because they are safe for the living body as they are biocompatible. Biomaterials can be loaded with bFGF and delivered locally to achieve the goal of sustained bFGF release. In the present review, we report different types of biomaterials that are used for bFGF delivery for nerve repair and briefly report how the introduced bFGF can function in the nervous system. We aim to provide summative guidance for future studies about nerve injury using bFGF.

Modified CFBP-bFGF targeting to ischemic brain promoted the functional recovery of cerebral ischemia.

The cerebral ischemia was one of the most common causes of disability and death worldwide. Basic fibroblast growth factor (bFGF) was reported to have neuroprotective function as well as promoting angiogenesis in the ischemic brain, but the targeting delivery of bFGF to ischemic brain was still difficult. In present study, a specific peptide was used to modify bFGF to construct recombinant CFBP-bFGF, and CFBP-bFGF could specifically deliver to ischemic brain through binding with the upregulated protein-connective tissue growth factor (CTGF). When CFBP-bFGF was used in rats with cerebral ischemia by intravenous injection, local concentration of the bFGF in ischemic brain was significantly increased. In addition, enhanced neurons survival, increased angiogenesis, decreased neuroinflammation were observed, that improved the motor functional recovery of cerebral ischemic injury. These results demonstrated that the targeting delivery of CFBP-bFGF would be a potential therapeutic approach for cerebral ischemia.

Stability Enhancement of Freeze-Dried Gelatin/Alginate Coacervates for bFGF Delivery.

Chronic wound sites have elevated levels of proteolytic enzymes that negate the activity of topically applied growth factors. bFGF encapsulated in gelatin/alginate coacervates was protected from protease and showed better activity than bFGF in solution; however, its activity decreased with particle size and PDI increase after freeze-drying and rehydration. In this study, we aim to improve the stability of bFGF coacervates during freeze-drying to enable a topically applied growth factor delivery system for diabetic foot ulcer. Trehalose, mannitol, and Tween 80 at various concentrations were tested as cryoprotectant candidates. Trehalose improved the mechanical property of freeze-dried coacervates and physical properties after rehydration, resulting in stable size and PDI values. It also enhanced the bFGF activity in hyperglycemic human dermal fibroblasts with better cell viability, migration, and procollagen synthesis compared to the coacervates without trehalose. Hydrogen bonding interactions between trehalose and polymers probed by ATR-FTIR contribute to the stability of coacervates during freeze-drying. In conclusion, the freeze-dried gelatin/alginate coacervates encapsulating bFGF was effectively stabilized with trehalose, and the resulting coacervate composition is suggested as a potential therapeutic modality for chronic wounds including diabetic foot ulcer.

Transdermal delivery of bFGF with sonophoresis facilitated by chitosan nanocarriers

The basic fibroblast growth factor (bFGF) is a potent angiogenic growth factor. Supplemental bFGF is essential for healing damaged skin, but its therapeutic use has been limited owing to its inherent instability. In this study, we propose a transdermal delivery system using sonophoresis along with the use of carboxymethyl chitosan nanocarriers which enables the administration of bFGF over a wide area of skin. The transdermal effect of the low-frequency ultrasound-enhanced delivery system was demonstrated in ex vivo experiments using hairless mouse skin. The subcutaneous administration of chitosan nanoparticles was evaluated by using fluorescence-labeled chitosan. To stably load bFGF into chitosan nanoparticles, a carrier with carboxymethyl chitosan was synthesized under a pH of around 7. Based on the results, we evaluated the effectiveness of transdermal drug delivery using sonophoresis. In skin cryosections, bFGF-loaded carboxymethyl chitosan nanocarriers delivered by ultrasound irradiation were present subcutaneously. We analyzed the bFGF content in skin tissue by ELISA and found that bFGF penetration in skin irradiated by ultrasound with nanocarriers. Penetration of bFGF-leaded carboxymethyl chitosan nanocarriers by ultrasound was significantly higher than that by ultrasound irradiation alone. Our results lay the groundwork for further utilization of polymeric nanocarriers using sonophoresis for the administration of biomacromolecules.

Polyphenol-Coordinated Supramolecular Hydrogel as a Promising “One-Stop-Shop” Strategy for Acute Infected Wound Treatment

The management and treatment of acute infected wounds, which are characterized by bacterial infections and excessive amount of reactive oxygen species, remains a major challenge in clinic. Herein, a facile and universal approach for constructing polyphenol-coordinated supramolecular hydrogel is developed for acute infected wound treatment. The hydrogels are mainly crosslinked via two types of noncovalent bond associations, i.e., the intermolecular hydrogen bonding between polyphenols and poly-vinylpyrrolidone/basic fibroblast growth factor (bFGF) components, and the metal-phenolic hydroxyl coordination interactions. Taking tannic acid (TA) as a model polyphenol for biomedical application, TA-based hydrogel (TPFe or TPFe/bFGF hydrogel) is demonstrated to possess multifunctional features, including: 1) potent adhesive capacity for adhesion to the wounds or cementing two separated tissues together; 2) hemostatic property against rats’ tail cut, liver incision, and heart hole bleeding within a few minutes; 3) antioxidant ability for DPPH and ABTS radical scavenging activities; 4) antibacterial activity especially for Staphylococcus aureus; 5) accelerated endothelial cells migration/proliferation and angiogenesis, which are attributed to bFGF delivery from the hydrogel. In vitro/vivo experimental results show that TPFe hydrogel has excellent biocompatibility, and faster healing rates are observed in animal tests whether with a full-thickness skin defect model or a bacterial-infected wound model. Hence, our work reveals that such supramolecular hydrogel with multiple functions may be well adaptive to the different stages of wound repair process, and thus highlights its great prospect as a promising “One-Stop-Shop” strategy for acute infected wound treatment.

An injectable and photocurable methacrylate-silk fibroin hydrogel loaded with bFGF for spinal cord regeneration

The treatment of spinal cord injury is still a major clinical challenge today. Basic fibroblast growth factor (bFGF) is a biological factor that effectively promotes the recovery of nerve function after spinal cord injury. The focus of this study was to accurately and efficiently maximize the biological effects of bFGF locally. Therefore, we innovatively synthesized methacrylate-silk fibroin (SilMA) hydrogels for bFGF delivery. This hydrogel has photocurable properties and form a gel upon UV in 15 s. The hydrogel shows no obvious cytotoxicity in vitro and in vivo. Our results showed that SilMA@bFGF can releases bFGF slowly to promote the regeneration of nerve axons, inhibit glial cell proliferation and improve neuronal mitochondrial function. In the early stage of spinal cord injury in rats, the SilMA hydrogel also inhibit the local inflammatory reaction and oxidative stress compared with injury alone, which is more conducive to the repair of nerve function. This study is the first to apply a photocurable silk fibroin hydrogel to spinal cord injury and the result is satisfactory. This method will provide a new treatment strategy for spinal cord injury.

Comparative Effects of Basic Fibroblast Growth Factor Delivery or Voluntary Exercise on Muscle Regeneration after Volumetric Muscle Loss.

Volumetric muscle loss (VML) is associated with irreversibly impaired muscle function due to traumatic injury. Experimental approaches to treat VML include the delivery of basic fibroblast growth factor (bFGF) or rehabilitative exercise. The objective of this study was to compare the effects of spatially nanopatterned collagen scaffold implants with either bFGF delivery or in conjunction with voluntary exercise. Aligned nanofibrillar collagen scaffold bundles were adsorbed with bFGF, and the bioactivity of bFGF-laden scaffolds was examined by skeletal myoblast or endothelial cell proliferation. The therapeutic efficacy of scaffold implants with either bFGF release or exercise was examined in a murine VML model. Our results show an initial burst release of bFGF from the scaffolds, followed by a slower release over 21 days. The released bFGF induced myoblast and endothelial cell proliferation in vitro. After 3 weeks of implantation in a mouse VML model, twitch force generation was significantly higher in mice treated with bFGF-laden scaffolds compared to bFGF-laden scaffolds with exercise. However, myofiber density was not significantly improved with bFGF scaffolds or voluntary exercise. In contrast, the scaffold implant with exercise induced more re-innervation than all other groups. These results highlight the differential effects of bFGF and exercise on muscle regeneration.

Gelatin-Alginate Coacervates Optimized by DOE to Improve Delivery of bFGF for Wound Healing.

Metabolic disorders in diabetic patients are associated with altered protein and lipid metabolism and defects in granulation tissue formation, resulting in non-healing wounds such as diabetic foot ulcers (DFU). Growth factors have essential roles in tissue re-epithelization and angiogenesis during wound healing. In this study, a complex coacervate was evaluated as an enhanced delivery system for fibroblast growth factor (bFGF) to control its release rate and protect it from proteases. Coacervates composed of gelatin Type A (GA) and sodium alginate (SA) were optimized by the Design of Experiments (DOE), with the polymer ratio and the medium’s pH as the independent variables, and turbidity, particle size, polydispersity index, and encapsulation efficiency (EE, %) as the responses. The optimized coacervate protected bFGF from trypsin digestion and showed controlled release compared with bFGF in solution or a physical mixture of GA and SA. It enhanced the viability, migration, and procollagen I C-terminal propeptide synthesis of human dermal fibroblasts in hyperglycemic conditions. In summary, the DOE approach was successfully applied to optimize bFGF GA-SA coacervates as a potential novel therapeutic modality to treat DFU.

Super-assembled core/shell fibrous frameworks with dual growth factors for in situ cementum-ligament-bone complex regeneration.

The regeneration of periodontal tissue defects remains a clinical challenge due to its complex tissue structure (e.g. periodontal ligament, alveolar bone and cementum) and poor self-healing ability. In situ tissue engineering has emerged as a promising approach that combines frameworks with growth factors that are specifically chosen for the recruitment of endogenous stem cells to the site of injury and to evoke the innate regenerative potential of the body. Herein, a core/shell fibrous super-assembled framework (SAF)-based sequential growth factor delivery system is developed, in which basic fibroblast growth factor (bFGF) and bone morphogenetic protein-2 (BMP-2) are designed to release in a sequential manner to facilitate in situ regeneration of the cementum-ligament-bone complex. The in situ tissue engineering framework (iTE-framework) shows ameliorated physicochemical properties and improved hydrophilicity, with an initial burst release of bFGF in the first few days, followed by a slow and constant release of BMP-2 up to 4 weeks. The iTE-framework shows excellent biocompatibility, significantly promoting the proliferation, migration and osteogenic differentiation of human periodontal ligament stem cells (PDLSCs) in vitro. After implantation in rat periodontal defects, the iTE-framework effectively triggers the recruitment of mesenchymal stem cells (MSCs) to the defect site, significantly promotes the formation of new bones, and facilitates the regeneration of the periodontal ligament and cementum tissue in vivo. Therefore, this sequential delivery system provides a promising therapeutic strategy for cementum-ligament-bone complex regeneration.

Dual growth factor delivery using PLGA nanoparticles in silk fibroin/PEGDMA hydrogels for articular cartilage tissue engineering.

Degeneration of articular cartilage due to damages, diseases, or age-related factors can significantly decrease the mobility of the patients. Various tissue engineering approaches which take advantage of stem cells and growth factors in a three-dimensional constructs have been used for reconstructing articular tissue. Proliferative impact of basic fibroblast growth factor (bFGF) and chondrogenic differentiation effect of transforming growth factor-beta 1 (TGF-β1) over mesenchymal stem cells have previously been verified. In this study, silk fibroin (SF) and of poly(ethylene glycol) dimethacrylate (PEGDMA) were used to provide a versatile platform for preparing hydrogels with tunable mechanical, swelling and degradation properties through physical and chemical crosslinking as a microenvironment for chondrogenic differentiation in the presence of bFGF and TGF-β1 releasing nanoparticles (NPs) for the first time. Scaffolds with compressive moduli ranging from 95.70 ± 17.82 to 338.05 ± 38.24 kPa were obtained by changing both concentration PEGDMA and volume ratio of PEGDMA with 8% SF. Highest cell viability was observed in PEGDMA 10%-SF 8% (1:1) [PEG10-SF8(1:1)] hydrogel group. Release of bFGF and TGF-β1 within PEG10-SF8(1:1) hydrogels resulted in higher DNA and glycosaminoglycans amounts indicating synergistic effect of dual release over proliferation and chondrogenic differentiation of dental pulp stem cells in hydrogels, respectively. Our results suggested that simultaneous delivery of bFGF and TGF-β1 through utilization of PLGA NPs within PEG10-SF8(1:1) hydrogel provided a novel and versatile means for articular cartilage regeneration as they allow for dosage- and site-specific multiple growth factor delivery.

Spatiotemporal delivery of basic fibroblast growth factor to directly and simultaneously attenuate cardiac fibrosis and promote cardiac tissue vascularization following myocardial infarction

Following myocardial infarction (MI), the destruction of vasculature in the infarcted heart muscle and progression of cardiac fibrosis lead to cardiac function deterioration. Vascularization of the damaged tissue and prevention of cardiac fibrosis represent promising strategies to improve cardiac function. Herein we have developed a bFGF release system with suitable release kinetics to simultaneously achieve the two goals. The release system was based on an injectable, thermosensitive, and fast gelation hydrogel and bFGF. The hydrogel had gelation time <7 s. It can quickly solidify upon injection into tissue so as to increase drug retention in the tissue. Hydrogel complex modulus can be tuned by hydrogel solution concentration. The complex modulus of 176.6 Pa and lower allowed cardiac fibroblast to maintain its phenotype. Bioactive bFGF was able to gradually release from the hydrogel for 4 weeks. The released bFGF promoted cardiac fibroblast survival under ischemic conditions mimicking those of the infarcted hearts. It also attenuated cardiac fibroblasts from differentiating into myofibroblasts in the presence of TGFβ when tested in 3D collagen model mimicking the scenario when the bFGF release system was injected into hearts. Furthermore, the released bFGF stimulated human umbilical endothelial cells to form endothelial lumen. After 4 weeks of implantation into infarcted hearts, the bFGF release system significantly increased blood vessel density, decreased myofibroblast density and collagen content, augmented cardiac cell survival/proliferation, and reduced macrophage density. In addition, the bFGF release system significantly increased cardiac function. These results demonstrate that delivery of bFGF with appropriate release kinetics alone may represent an efficient approach to control cardiac remodeling after MI.

Sequential application of bFGF and BMP-2 facilitates osteogenic differentiation of human periodontal ligament stem cells.

Basic fibroblast growth factor (bFGF) promotes cells proliferation and chemotaxis and maintains stemness while inhibits mineralized nodule formation. Bone morphogenetic protein 2 (BMP-2) shows great potential in promoting bone formation. However, sequential application of these two growth factors on periodontal ligament stem cells (PDLSCs) has not been explored. In this study, we aimed to identify the optimal concentration and time of bFGF on PDLSCs proliferation, migration and then investigate the sequential delivery of bFGF and BMP-2 on osteogenic differentiation of PDLSCs in vitro. Periodontal ligament stem cells were isolated by limiting dilution method. Dose-dependent additive effects of bFGF and BMP-2 on PDLSCs were detected. Cell counting assay, cell migration assay, alkaline phosphatase (ALP) activity assay, Alizarin red staining, quantitative real-time polymerase chain reaction (qRT-PCR), and western blot analysis were used to determine different application modalities of bFGF and BMP-2 on proliferation, migration, and osteogenic differentiation of PDLSCs. 50ng/mL bFGF significantly promoted PDLSCs proliferation and chemotaxis while time-dependently inhibited BMP-2 induced ALP activity. Sequential application of 25ng/mL bFGF for first 3days and followed with 50ng/mL BMP-2 for another 9, 18, and 25days significantly promoted PDLSCs osteogenic differentiation. Compared with bFGF and BMP-2 simultaneous group, sequential application of bFGF and BMP-2 group significantly enhanced ALP activity, osteogenesis-related genes and proteins expression and mineral deposition. Sequential application of bFGF and BMP-2 synergistically promoted osteogenic differentiation of PDLSCs, and this sequential application modality of growth factors would provide a new strategy for periodontal regeneration.

Modelling optimal delivery of bFGF to chronic wounds using ODEs

In this paper, we present an ordinary differential equation model depicting the interactions of basic fibroblast growth factor (bFGF) and its binding agents in a chronic wound. The delivery of bFGF was treated as a control variable and is coupled to an objective functional. By optimising the objective functional with respect to the control, predictions for optimal delivery rates of bFGF are proposed. The optimal control is then validated by comparing the cost of the objective functional for the optimal delivery rate and several alternative delivery rates.This paper addresses two objectives of effective drug delivery to chronic wounds. The first is to provide insight for the priority of delivering bFGF: to minimise the quantity of bFGF, or to optimise the distribution of bound bFGF. For effective concentrations of bound bFGF, the optimisation of bound bFGF must be prioritised over the minimisation of bFGF delivered. The second objective is to comment on the effect of the proteolytic environment within the wound, with the concentration of bound bFGF starting to decrease late in the treatment period for highly proteolytic environments. This will lead to long term complications with wound closure after the treatment has been completed. Also, it was found that for highly proteolytic environments, the cost of delivering bFGF increased. The need for optimal drug delivery is made apparent by the burden of chronic wounds on the medical industry across the developed world.

Collagen/Heparin Bi-Affinity Multilayer Modified Collagen Scaffolds for Controlled bFGF Release to Improve Angiogenesis In Vivo.

Basic fibroblast growth factor (bFGF) is an important protein for wound healing and angiogenesis in tissue engineering, but the lack of a viable delivery system hampers its clinical application. This study aims to maintain the long-term controlled release of bFGF by utilizing a collagen/heparin bi-affinity multilayer delivery system (CHBMDS), which is fabricated by the alternate deposition of negatively charged heparin, positively charged collagen, and CBD-bFGF (a collagen-binding domain [CBD] was fused into the native bFGF) via specific or electrostatic interaction. The results show that CHBMDS not only support localized and prolonged release of CBD-bFGF(over 35 days) but also lead to enhanced angiogenesis (higher density and larger diameter (≈70 µm) of newly formed blood vessels in subcutaneous tissue of SD rat after 5 weeks). This system could act as a versatile approach for bFGF delivery and further improve therapeutic efficacy for injured tissues.

The dual delivery of KGF and bFGF by collagen membrane to promote skin wound healing.

The major challenges associated with skin regeneration can include hindered vascularization and an insufficient degree of epithelization. In view of the complexity of these processes and the control signals on which they depend, one possible solution to these limitations could be simulating normal skin development and wound repair via the exogenous delivery of multiple cytokines. Here, we report the use of keratinocyte growth factor (KGF or FGF-7) and basic fibroblast growth factor (bFGF or FGF-2) released chemically modified collagen membranes to facilitate skin wound healing. The results from in vitro studies confirmed that this system resulted in higher cellular proliferation and faster cell migration. After transplanting the biomaterial onto an excisional wound healing model, the dual growth factor group, compared with the single growth factor groups and empty control group, showed more highly developed vascular networks and organized epidermal regeneration in the wounds. As a consequence, this experimental group showed mature epidermal coverage. Overall, this novel approach of releasing growth factors from a collagen membrane opens new avenues for fulfilling unmet clinical needs for wound care.

Synergistic delivery of bFGF and BMP-2 from poly(l-lactic-co-glycolic acid)/graphene oxide/hydroxyapatite nanofibre scaffolds for bone tissue engineering applications.

One of the goals of bone tissue engineering is to create scaffolds with excellent biocompatibility, osteoinductive ability and mechanical properties. The application of bioactive proteins, such as bone morphogenetic protein (BMP)-2 and basic fibroblast growth factor (bFGF), has been showed to be an effective way to improve the osteoinductivity and biocompatibility of bone scaffold materials. Therefore, the development of novel materials capable of delivering multiple growth factors is urgent and essential for bone defect repair. In this study, a composite nanofibre scaffold composed of poly(l-lactic-co-glycolic acid) (PLGA), hydroxyapatite (HA), and graphene oxide (GO) has been fabricated to deliver basic fibroblast growth factor (bFGF) and bone morphogenetic protein-2 (BMP-2) simultaneously. The data show that the incorporation of GO and HA into PLGA nanofibres significantly improved the mechanical properties and hydrophilicity of the nanofibre scaffolds. More importantly, compared to PLGA and PLGA/HA nanofibre scaffolds, the PLGA/HA/GO nanofibre scaffolds could more efficiently immobilize bFGF and BMP-2. Moreover, biological assays indicated that the loaded bFGF and BMP-2 loaded in the composite nanofibre scaffolds have a synergistic differentiation effect on the cell adhesion, proliferation, and osteogenesis differentiation of MC3T3-E1 cells. In contrast to the PLGA/HA/GO/bFGF and PLGA/HA/GO/BMP-2 nanofibre scaffolds, the PLGA/HA/GO/bFGF/BMP-2 scaffolds have shown higher ALP activity and higher expression levels of osteogenesis-related genes. In summary, our findings indicated that the incorporation of GO into nanofibre scaffolds is an effective method to immobilize growth factors onto biomaterial surfaces, and the synergistic effects of a combination of BMP-2 and bFGF may have potential use in bone regenerative therapeutics.