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Efficient osseointegration is a key factor in dental implants to reduce the total time-course of therapy. Titanium implants with anodized surface gained much interest for their enhanced osseointegration. Anodized implant combined with bioactive drugs is an ideal candidate for enhance bone regeneration. Previously delivery of drugs from the metal implants has been attempted by utilizing a polymeric dip-coating method. However, the entire surface coating with polymer can diminish the advantageous surface roughness of anodized implants and cause contact inhibition between bone and implant surface. In this study, fibroblast growth factor-2 (FGF-2) loaded poly(lactide-co-glycolide) nanoparticles were partially coated on anodized Ti discs by an electrospray deposition. Nanoparticle coated anodized discs maintained their native porous structure and provided a sustained release of FGF-2 for more than 2 weeks with 40% initial burst. In vitro study confirmed the influence of polymeric nanoparticles and the release of growth factors from the Ti disc. Nanoparticle-coated groups significantly enhanced cell spreading and differentiation. For in vivo evaluation, the anodized titanium implants were applied to rabbit tibia model. The osseointegration was estimated by bone to implant contact of best three consecutive threads at the border of the implant. The mean osteointegration value of FGF-2 releasing implant groups (70.1%) was significantly higher than that of untreated implants (47.1%). We believe that the electrospray deposition technique is a particularly attractive approach for the coating of medical devices with porous surface to maintain their surface topography while allowing a sustained delivery of growth factors for bone regeneration. © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 102A: 3639-3648, 2014., (© 2013 Wiley Periodicals, Inc.)

Poly(L-lactic acid) (PLLA) microfibrous scaffolds with three-dimensional (3D) structures were fabricated using an electrospinning technique with a subsequent mechanical expansion process. To achieve a 3D fibrous structure, the fusion at the contact points of the as-spun PLLA microfibers was avoided using an appropriate binary solvent system of methylene chloride and acetone. The solvent composition was optimized based on the solvent power, volatility, and viscosity (methylene chloride:acetone = 9:1 volume ratio). The final 3D structure of the electrospun scaffolds was obtained after mechanical expansion of the electrospun microfibrous mats. The pore sizes of the scaffolds were controlled by varying the degree of expansion of the nonbonded microfibrous mats, and they were in the range of several microns up to 400 μm. The 3D scaffolds were examined for their morphological properties and their potential use for the proliferation of osteoblasts. Generally recognized electrospun 2D nanofibrous membranes were also tested in order to compare the cell behaviors using different scaffold geometries. The 3D scaffolds demonstrated a high level of osteoblast proliferation (1.8-fold higher than nanofibrous membranes in a week). The osteoblasts actively penetrated the inside of the 3D scaffold and showed a spatial cell distribution, as confirmed by SEM and H&E staining, while a monolayer formed in the case of the 2D nanofibrous membranes with limited cell infiltration. In vivo results further showed that 3D electrospun microfibrous matrices were a favorable substrate for cell infiltration and bone formation after 2 and 4 weeks, using a rabbit calvarial defect model. In this study, the 3D microfibrous PLLA scaffolds fabricated using electrospinning techniques might be an innovative addition to tissue engineering applications.

A chitosan/poly(L-lactic acid) (PLLA) multilayered membrane was prepared for the purpose of guided tissue regeneration (GTR). The membrane was composed of the outer layers of chitosan mesh and the middle layer of nanoporous PLLA membrane. The outer membranes of chitosan fibrous mesh present a highly biocompatible and rough surface for ease of cell adherence. The PLLA membrane is intended to provide mechanical strength to the membrane, thereby preventing epithelial invasion. The PLLA membrane was applied as a local drug delivery carrier for growth factors. Regular pores in PLLA membrane were generated through phase inversion of polymer solution. The membrane retained its integrity during the degradation process in vitro (for up to 8 weeks), which is a requirement for providing enough space in vivo in the GTR procedure. Osteoblasts firmly attached to broad cytoplasmic extensions along with the microfibers of the membrane. The phenotypic expression of cultured osteoblasts on the membrane was measured by a reverse transcriptase-polymerase chain reaction. New bone had formed beneath the chitosan/PLLA membrane. These results suggested that the chitosan/PLLA membranes properly functioned as biocompatible and mechanically stable barriers for GTR.

With an aim to mimic natural extracellular matrix, we fabricated the nano- and microfibrous matrix with chitosan by electrospinning nanofibers onto predefined microfibrous mesh for effective chondrocytes cultivation. Rolling the double-layered nano-/microfibrous membranes produced three-dimensional (3-D) scaffolds that exhibited the interconnected open pore structure in their scanning electron microscopy images. In vitro chondrocyte culture experiment showed that this nano-/microfibrous 3-D matrix provided a significantly greater microenvironment for chondrocytes to proliferate and produce glycosaminoglycan as compared with only microfibrous 3-D matrix. This difference could be explained by the result on 2-D membrane, where chitosan nanofibrous surface substantially facilitated the cellular attachment and proliferation, and efficiently prevented phenotypic changes of chondrocytes, when compared with chitosan microfibrous membrane and film. In this regard, the nano-/microfibrous 3-D matrix we fabricated in this study would possess a great potential as a system for effective chondrocyte cultivation and also for application to cartilage regeneration therapy.

Novel chitosan-poly(lactide-co-glycolide) (PLGA) composite fibers and nonwoven fibrous scaffolding matrices were designed for cartilage regeneration. A homogenous one-phase mixture of chitosan and PLGA at a ratio of 50:50 (w/w %) was successfully produced using cosolvents of 1,1,1,3,3,3-hexafluoroisopropanol and methylene chloride. A wet spinning technique was employed to fabricate composite fibrous matrices. Physical characterizations of one-phase chitosan-PLGA composite (C/Pc) matrices were performed for their homogeneity, in vitro degradability, mechanical property and wettability in comparison to two-phase chitosan and PLGA composite fibrous matrices in which PLGA was dispersed in a continuous chitosan phase. The one-phase property of C/Pc matrices was confirmed from thermal analysis. Significantly retarded degradation was observed from the composite C/Pc fibrous matrices in contrast to the PLGA-dispersed chitosan (C/Pd) fibrous matrices due to the effective acid-neutralizing effect of chitosan on acid metabolites of PLGA. The composition of chitosan with PLGA resulted in a characteristic soft and strong mechanical property that could not be retained by either PLGA or the chitosan fibers. In addition, the presence of chitosan in the composite matrices provided proper wettability for cell cultivation. The C/Pc matrices were further investigated for their scaffolding function using chondrocytes for cartilage regeneration. Enhanced cell attachment was observed on the composite matrix compared with the PLGA fibrous matrices. The mRNA expression of type II collagen and aggrecan was upregulated in the composite matrix owing to the superior cell compatibility of chitosan. These results suggest an excellent potential for C/Pc one-phase composite fibrous matrices as scaffolding materials for tissue regeneration., ((c) 2007 Wiley Periodicals, Inc. J Biomed Mater Res, 2008.)