Electrospun Polycaprolactone Scaffolds Research Articles

Non-solvent effect on the fiber diameter of electrospun polycaprolactone scaffolds

Non-solvent effect on the fiber diameter of electrospun polycaprolactone scaffolds

Effect of humidity on melt electrospun polycaprolactone scaffolds

AbstractDirect write melt electrospinning is an additive manufacturing technique used to produce 3D polymer scaffolds for tissue engineering applications. It is similar to conventional 3D printing by layering 2D patterns to build up an object, but uses a high-electric potential to draw out fibres into micron-scale diameters with great precision. Direct write melt electrospinning is related to a well-established fabrication technique, solution electrospinning, but extrudes a melted polymer in a controlled manner rather than a polymer solution. The effect of environmental conditions such as humidity has been extensively studied in the context of solution electrospinning; however, there is a lack of similar studies for direct write melt electrospinning. In this study, melt electrospun polycaprolactone scaffolds were produced with 90 degree cross-hatch architecture at three specific humidity [

Preliminary Investigation and Characterization of Electrospun Polycaprolactone and Manuka Honey Scaffolds for Dermal Repair

This study focused on the characterization of Manuka honey-containing poly(ε-caprolactone) (PCL) nanofiber scaffolds with regards to wound healing. Scaffolds were electrospun from 1, 5, 10, and 20% v/v Manuka honey solutions. Scaffolds were subjected to ethanol disinfection and soaked in phosphate-buffered saline (PBS) for various timepoints, and scaffold morphology and honey release was quantified. Scaffolds showed increased water vapor transmission rate (WVTR) with scaffold soak time, indicating an increase in evaporation due to enhanced osmotic potential of the scaffolds. Mechanical testing indicated lower elasticity and strength with honey incorporation, but showed no significant change in material degradation rate with the presence of honey over a 28 day PBS soak. Fibroblast studies showed honey incorporation increased cell infiltration into the scaffold, but scaffold conditioned media did not induce significant chemotaxis towards the scaffold. Honey incorporation also demonstrated an increase in fibroblast proliferation when in direct contact with the scaffolds. Bacterial clearance from pure honey was observed in both Gram positive Streptococcus agalactiae (Group B Streptocococcus) and Gram negative Escherichia coli ( E. coli), but honey scaffolds demonstrated significant clearance in only the Gram negative E. coli. While further investigation is needed, this preliminary study demonstrates the wound-healing potential of Manuka honey-loaded electrospun scaffolds.

In vivo evaluation of electrospun polycaprolactone graft for anterior cruciate ligament engineering.

The anterior cruciate ligament (ACL) is critical for the structural stability of the knee and its injury often requires surgical intervention. Because current reconstruction methods using autograft or allograft tissue suffer from donor-site morbidity and limited supply, there has been emerging interest in the use of bioengineered materials as a platform for ligament reconstruction. Here, we report the use of electrospun polycaprolactone (PCL) scaffolds as a candidate platform for ACL reconstruction in an in vivo rodent model. Electrospun PCL was fabricated and laser cut to facilitate induction of cells and collagen deposition and used to reconstruct the rat ACL. Histological analysis at 2, 6, and 12 weeks postimplantation revealed biological integration, minimal immune response, and the gradual infiltration of collagen in both the bone tunnel and intra-articular regions of the scaffold. Biomechanical testing demonstrated that the PCL graft failure load and stiffness at 12 weeks postimplantation (13.27±4.20N, 15.98±5.03 N/mm) increased compared to time zero testing (3.95±0.33N, 1.95±0.35 N/mm). Taken together, these results suggest that electrospun PCL serves as a biocompatible graft for ACL reconstruction with the capacity to facilitate collagen deposition.

Sustained Release of Hydrophilic l-ascorbic acid 2-phosphate Magnesium from Electrospun Polycaprolactone Scaffold-A Study across Blend, Coaxial, and Emulsion Electrospinning Techniques.

The purpose of this study was to achieve a sustained release of hydrophilic l-ascorbic acid 2-phosphate magnesium (ASP) from electrospun polycaprolactone (PCL) scaffolds, so as to promote the osteogenic differentiation of stem cells for bone tissue engineering (TE). ASP was loaded and electrospun together with PCL via three electrospinning techniques, i.e., coaxial, emulsion, and blend electrospinning. For blend electrospinning, binary solvent systems of dichloromethane–methanol (DCM–MeOH) and dichloromethane–dimethylformamide (DCM–DMF) were used to achieve the desired ASP release through the effect of solvent polarity and volatility. The scaffold prepared via a blend electrospinning technique with a binary solvent system of DCM–MeOH at a 7:3 ratio demonstrated a desirable, sustained ASP release profile for as long as two weeks, with minimal burst release. However, an undesirable burst release (~100%) was observed within the first 24 h for scaffolds prepared by coaxial electrospinning. Scaffolds prepared by emulsion electrospinning displayed poorer mechanical properties. Sustained releasing blend electrospun scaffold could be a good potential candidate as an ASP-eluting scaffold for bone tissue engineering.

In vitro and in vivo evaluation of heparin mediated growth factor release from tissue-engineered constructs for anterior cruciate ligament reconstruction.

Anterior cruciate ligament (ACL) rupture is a common injury often necessitating surgical treatment with graft reconstruction. Due to limitations associated with current graft options, there is interest in a tissue-engineered substitute for use in ACL regeneration. While they represent an important step in translation to clinical practice, relatively few in vivo studies have been performed to evaluate tissue-engineered ACL grafts. In the present study, we immobilized heparin onto electrospun polycaprolactone scaffolds as a means of incorporating basic fibroblast growth factor (bFGF) onto the scaffold. In vitro, we demonstrated that human foreskin fibroblasts (HFFs) cultured on bFGF-coated scaffolds had significantly greater cell proliferation. In vivo, we implanted electrospun polycaprolactone grafts with and without bFGF into athymic rat knees. We analyzed the regenerated ACL using histological methods up to 16 weeks post-implantation. Hematoxylin and eosin staining demonstrated infiltration of the grafts with cells, and picrosirius red staining demonstrated aligned collagen fibers. At 16 weeks postop, mechanical testing of the grafts demonstrated that the grafts had approximately 30% the maximum load to failure of the native ACL. However, there were no significant differences observed between the graft groups with or without heparin-immobilized bFGF. While this study demonstrates the potential of a regenerative medicine approach to treatment of ACL rupture, it also demonstrates that in vitro results do not always predict what will occur in vivo.

Abstract 4941: A humanized bone model for preclinical monitoring of prostate cancer lesions by intravital multiphoton microscopy

Abstract Bone metastases are the initial site of progression and account for many of the complications experienced by men with metastatic prostate cancer (PCa), including resistance to therapy. The purpose of our study is to determine whether intravital multiphoton microscopy (iMPM) integrated with a novel mouse model can better inform clinical development of molecular therapeutics targeting bone metastases. iMPM can overcome limitations of existing models by monitoring the dynamic reciprocal cell-cell interplay at the center of PCa bone metastasis. To study PCa-stromal cell interactions and therapy response in bone, we established a humanized neo-bone in the mouse dermis, using grafted electrospun polycaprolactone scaffolds functionalized with human mesenchymal stem cells differentiated to osteoblasts. After in vivo maturation, bone scaffolds served for co-implantation of human fluorescent PCa cells (PC3) followed by multi-parameter iMPM through a body window, including: collagen and bone matrix (second harmonic generation), mineralized matrix (calcein blue), osteoblasts (H2B/mCherry in human mesenchymal stem cells), adipocytes and bone surface (third harmonic generation), blood vessels, stromal phagocytes and osteoclasts (fluorescence-labeled dextran), and PC3 cells (nuclear H2B eGFP with cytoplasmatic DsRed2). Using multi-parameter 3D reconstruction, tumor growth and invasion, reactive remodeling of the stroma and neovessel organization were monitored longitudinally, providing a baseline for evaluating preclinical disease and therapy response. The model provides new insight into PCa bone metastases and will be used to more efficiently develop and prioritize biologically founded therapy for clinical development. Citation Format: Eleonora Dondossola, Stephanie Alexander, Steve Alexander, Boris M. Holzapfel, Christopher J. Logothetis, Dietmar W. Hutmacher, Peter Friedl. A humanized bone model for preclinical monitoring of prostate cancer lesions by intravital multiphoton microscopy. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4941. doi:10.1158/1538-7445.AM2014-4941

Investigation of angiogenesis and its mechanism using zinc oxide nanoparticle-loaded electrospun tissue engineering scaffolds

Angiogenesis through tissue engineering scaffolds is an important factor that determines the success of a tissue engineering endeavor. Zinc oxide (ZnO) nanoparticles are well known for their ability to generate reactive oxygen species (ROS) which have a potential role in biological systems. ROS can induce angiogenesis through growth factor mediated mechanisms. Here, we report the fabrication of electrospun polycaprolactone scaffolds incorporated with ZnO nanoparticles and their ability to induce angiogenesis. This study demonstrated that the induction of angiogenesis was by the expression of key proangiogenic factors, fibroblast growth factor (FGF) and vascular endothelial growth factor (VEGF), upregulated due to the presence of ZnO nanoparticles. This is the first report suggesting the use of a metal/metal oxide nanoparticle in tissue engineering scaffolds to enhance angiogenesis.

Improvement of cell infiltration in electrospun polycaprolactone scaffolds for the construction of vascular grafts.

The less-than-ideal cell infiltration resulting from inherently small pore size limits the application of electrospinning scaffold in tissue engineering and regeneration medicine. The present study aims to develop a porogenic method which can significantly increase pore size in electrospinning scaffold and enhance cell migration. With this method, composite scaffolds consisting of poly(epsilon-caprolactone) (PCL) fibers and poly(ethylene oxide) (PEO) microparticles were prepared by simultaneously electrospinning and electrospraying. Removal of the PEO microparticles from the composites generated large pores. In vitro culture of NIH3T3 cells and in vivo subcutaneous implantation both demonstrated that the porogenic scaffolds markedly facilitated cell infiltration. With the same technique, vascular grafts with alternative dense and loose layers were prepared by turning on or off electrospraying PEO. SEM showed that there was no a clear delamination between the loose and dense layers. The mechanical strength and burst pressure of these vascular grafts could meet the requirements of vascular implantation. In conclusion, electrospinning PCL fibers with electrospraying PEO microparticles may be an effective and controllable method to increase pore size in electrospinning scaffold and provides a useful tool for the fabrication of vascular grafts that meets the need of blood vessel replacement.

The effect of thick fibers and large pores of electrospun poly(ε-caprolactone) vascular grafts on macrophage polarization and arterial regeneration

The vascular grafts prepared by electrospinning often have relatively small pores, which limit cell infiltration into the grafts and hinder the regeneration and remodeling of the grafts into neoarteries. To overcome this problem, macroporous electrospun polycaprolactone (PCL) scaffolds with thicker fibers (5–6 μm) and larger pores (∼30 μm) were fabricated in the present study. In vitro cell culture indicated that macrophages cultured on thicker-fiber scaffolds tended to polarize into the immunomodulatory and tissue remodeling (M2) phenotype, while those cultured on thinner-fiber scaffolds expressed proinflammatory (M1) phenotype. In vivo implantation by replacing rat abdominal aorta was performed and followed up for 7, 14, 28 and 100 d. The results demonstrated that the macroporous grafts markedly enhanced cell infiltration and extracellular matrix (ECM) secretion. All grafts showed satisfactory patency for up to 100 days. At day 100, the endothelium coverage was complete, and the regenerated smooth muscle layer was correctly organized with abundant ECM similar to those in the native arteries. More importantly, the regenerated arteries demonstrated contractile response to adrenaline and acetylcholine-induced relaxation. Analysis of the cellularization process revealed that the thicker-fiber scaffolds induced a large number of M2 macrophages to infiltrate into the graft wall. These macrophages further promoted cellular infiltration and vascularization. In conclusion, the present study confirmed that the scaffold structure can regulate macrophage phenotype. Our thicker-fiber electrospun PCL vascular grafts could enhance the vascular regeneration and remodeling process by mediating macrophage polarization into M2 phenotype, suggesting that our constructs may be a promising cell-free vascular graft candidate and are worthy for further in vivo evaluation.

Electrospun polycaprolactone membranes incorporated with ZnO nanoparticles as skin substitutes with enhanced fibroblast proliferation and wound healing

ZnO nanoparticles are well known for their ability to generate Reactive Oxygen Species (ROS) which have a potential role in biological systems. ROS can enhance wound healing by improved cell adhesion and cell migration through growth factor mediated pathways. Here we report the fabrication of electrospun polycaprolactone scaffolds incorporated with ZnO nanoparticles and their ability to perform as skin substitute materials which promote the healing process. The plain or ZnO nanoparticle incorporated PCL membranes were implanted subcutaneously in guinea pigs. Immunological, macroscopical and histological evaluations have shown that the use of membranes containing ZnO nanoparticles enhances the cell adhesion and migration. The ZnO nanoparticle embedded membranes do not show any significant sign of inflammation. The implant also enhanced the wound healing without any scar formation.

Recrystallization improves the mechanical properties of sintered electrospun polycaprolactone

BackgroundResorbable electrospun polycaprolactone (PCL) scaffolds for tissue reconstruction can provide physicians with an “off the shelf” product tailored to the patient's specific tissue architecture. However, many tissue-engineering platforms do not possess the necessary long-term mechanical stability needed to properly support tissue development. ObjectiveSintering has been explored as a means of altering the properties of electrospun PCL. However, crystallinity-driven changes in mechanical properties following thermal treatment have not been previously investigated. MethodsPCL nanofibers were produced by electrospinning and subsequently thermally sintered (at 55, 56 and 58°C) to enhance their long-term mechanical integrity in response to representative biological milieux. ResultsScaffolds initially sintered at 56°C displayed 6-fold increases in compressive strength and 3-fold increases in modulus, while displaying 10-fold increases in energy dissipation with increasing sintering temperature. Sintering just below the Tm resulted in amorphization of the 55°C sample as indicated by the 20-fold lower XRD peak intensities. Although crystallinity is suppressed, the polymer chains likely retain chain alignment from electrospinning and are apparently highly susceptible to recrystallization. After only 1d PBS exposure, the 55°C samples recover a substantial fraction of the as-spun crystallinity; 7d of exposure fully restores as-spun peak intensities. The mechanical properties of all three (55, 56, or 58°C) scaffolds displayed peak values of compressive strength and modulus following 7d exposure. ConclusionIn contrast with the current state-of-the-art which assumes that tissue engineering scaffolds only grow weaker following exposure, in these scaffolds maximum values of compressive strength and modulus were observed after 7d of aqueous immersion. This suggests that polymeric recrystallization can be used to increase or optimize mechanical properties in vitro/in vivo. Scaffolds that increase their mechanical integrity during biological exposures constitute a new pathway enabling clinical advances.

Integrin α5β1-mediated attachment of NIH/3T3 fibroblasts to fibronectin adsorbed onto electrospun polymer scaffolds

Protein adsorption and receptor-ligand binding are two key first steps in the cell adhesion process. The ability to predetermine the success or failure of these processes would significantly advance the field of tissue engineering. This study examines fibronectin adsorption on functionalized electrospun polycaprolactone (PCL) scaffolds and determines the affinity of cell receptors for the adsorbed fibronectin onto each scaffold. After determining the affinity values, model plots were developed for each scaffold type based on the amount of fibronectin on the surface of the scaffold. The ability to theoretically predict the level of cell binding to a tissue engineering scaffold would significantly impact the decision of what scaffold type to use for a specific application. Results show that aminated PCL scaffolds adsorb significantly more protein than hydrolyzed PCL scaffolds; however, greater α5β1–fibronectin binding occurs on the hydrolyzed scaffolds. This is attributed to a higher affinity between the receptors on the cell and the fibronectin adsorbed onto hydrolyzed scaffolds compared with aminated scaffolds., POLYM. ENG. SCI., 54:2587–2594, 2014. © 2013 Society of Plastics Engineers

The influence of cellular source on periodontal regeneration using calcium phosphate coated polycaprolactone scaffold supported cell sheets

Cell-based therapy is considered a promising approach to achieving predictable periodontal regeneration. In this study, the regenerative potential of cell sheets derived from different parts of the periodontium (gingival connective tissue, alveolar bone and periodontal ligament) were investigated in an athymic rat periodontal defect model. Periodontal ligament (PDLC), alveolar bone (ABC) and gingival margin-derived cells (GMC) were obtained from human donors. The osteogenic potential of the primary cultures was demonstrated in vitro. Cell sheets supported by a calcium phosphate coated melt electrospun polycaprolactone (CaP-PCL) scaffold were transplanted to denuded root surfaces in surgically created periodontal defects, and allowed to heal for 1 and 4 weeks. The CaP-PCL scaffold alone was able to promote alveolar bone formation within the defect after 4 weeks. The addition of ABC and PDLC sheets resulted in significant periodontal attachment formation. The GMC sheets did not promote periodontal regeneration on the root surface and inhibited bone formation within the CaP-PCL scaffold. In conclusion, the combination of either PDLC or ABC sheets with a CaP-PCL scaffold could promote periodontal regeneration, but ABC sheets were not as effective as PDLC sheets in promoting new attachment formation.

Fibronectin adsorption on functionalized electrospun polycaprolactone scaffolds: Experimental and molecular dynamics studies

Designing scaffolds to modulate protein adsorption is a key to building advanced scaffolds for tissue regeneration. Protein adsorption to tissue engineering scaffolds is critical in early cell attachment, survival, and eventual proliferation. The goal of this study is to examine the effect of functionalization on fibronectin adsorption to electrospun polycaprolactone (PCL) scaffolds through experimentation using fluorescently labeled fibronectin and to couple this experimental data with analysis of interaction energies obtained through molecular dynamics (MD) simulations to develop a better understanding of the adsorption process. This study is the first to analyze and compare experimental and MD simulation results of fibronectin adsorption on functionalized electrospun PCL scaffolds. Electrospun nanofiber PCL scaffolds were treated with either 1 N NaOH (hydrolyzed) or 46% hexamethylenediamine (HMD) (aminated) solution to be compared with untreated (control) scaffolds. We found that aminated PCL scaffolds experimentally adsorbed more fibronectin than control scaffolds, whereas hydrolyzed scaffolds showed decreased adsorption. MD simulations carried out with NVT ensemble at a temperature of 310 K indicated a higher work of adhesion for both functionalized scaffolds over control. Also, the simulations revealed different conformations of fibronectin on each scaffold type after adsorption, with the arginine-glycine-aspartic acid sequence appearing most accessible on the aminated scaffolds. This suggests that functionalization affects not only the quantity of protein that will adsorb on a scaffold but how it attaches as well, which could affect subsequent cell attachment.

Electrospun polycaprolactone scaffolds with tailored porosity using two approaches for enhanced cellular infiltration

The impact of mat porosity of polycaprolactone (PCL) electrospun fibers on the infiltration of neuron-like PC12 cells was evaluated using two different approaches. In the first method, bi-component aligned fiber mats were fabricated via the co-electrospinning of PCL with polyethylene oxide (PEO). Variation of the PEO flow rate, followed by selective removal of PEO from the PCL/PEO mesh, allowed for control of the porosity of the resulting scaffold. In the second method, aligned fiber mats were fabricated from various concentrations of PCL solutions to generate fibers with diameters between 0.13 ± 0.06 and 9.10 ± 4.1 μm. Of the approaches examined, the variation of PCL fiber diameter was found to be the better method for increasing the infiltration of PC12 cells, with the optimal infiltration into the ca. 1.5-mm-thick meshes observed for the mats with the largest fiber diameters, and hence largest pore sizes.

Self-assembling peptide-enriched electrospun polycaprolactone scaffolds promote the h-osteoblast adhesion and modulate differentiation-associated gene expression

Electrospun polycaprolactone (PCL) is able to support the adhesion and growth of h-osteoblasts and to delay their degradation rate to a greater extent with respect to other polyesters. The drawbacks linked to its employment in regenerative medicine arise from its hydrophobic nature and the lack of biochemical signals linked to it. This work reports on the attempt to add five different self-assembling (SA) peptides to PCL solutions before electrospinning. The hybrid scaffolds obtained had regular fibers (SEM analysis) whose diameters were similar to those of the extracellular matrix, more stable hydrophilic (contact angle measurement) surfaces, and an amorphous phase constrained by peptides (DSC analysis). They appeared to have a notable capacity to promote the h-osteoblast adhesion and differentiation process by increasing the gene expression of alkaline phosphatase, bone sialoprotein, and osteopontin. Adding an Arg-Gly-Asp (RGD) motif to a self-assembling sequence was found to enhance cell adhesion, while the same motif condensed with a scrambled sequence did not, indicating that there is a cooperative effect between RGD and 3D architecture created by the self-assembling peptides. The study demonstrates that self-assembling peptide scaffolds are still able to promote beneficial effects on h-osteoblasts even after they have been included in electrospun polycaprolactone. The possibility of linking biochemical messages to self-assembling peptides could lead the way to a 3D decoration of fibrous scaffolds.

Influence of hydration on fiber geometry in electrospun scaffolds

Finite element models of tissue engineering scaffolds are powerful tools to understand scaffold function, including how external mechanical signals deform the scaffold at the meso- and microscales. Fiber geometry is needed to inform finite element models of fiber-based tissue engineering scaffolds; however, the accuracy and utility of these models may be limited if they are informed by non-hydrated geometries. Scanning electron microscopy and confocal microscopy, coupled with Fourier analysis of the resulting images, were used to quantify how hydration alters fiber geometry in electrospun collagen and polycaprolactone (PCL) scaffolds. The results also quantify how image size affects fiber geometry. Hydration is demonstrated to increase fiber tortuosity, defined as the ratio of actual fiber length:end-to-end fiber length. For collagen scaffolds, hydration increased the mean tortuosity from 1.05 to 1.21, primarily from large ∼2- to 10-fold) increases in smaller (<40μm) wavelength amplitudes. For PCL fibers, the mean tortuosity increased from 1.01 to only 1.04, primarily from modest ∼2-fold) increases in larger (>100μm) wavelength amplitudes. The results demonstrate that mechanical simulations of electrospun scaffolds should be informed with hydrated scaffold geometries of at least 200μm scale, in order to capture geometrical effects associated with fiber straightening.

Vascular Wall Engineering Via Femtosecond Laser Ablation: Scaffolds with Self-Containing Smooth Muscle Cell Populations

For tissue-engineered vascular grafts to reach their full potential, three-dimensional (3D) cellular micro-integration will be necessary. In this study, we utilize femtosecond laser ablation to produce microchannels inside electrospun polycaprolactone (PCL) scaffolds. These microchannels potentially provide spatially controlled cell distributions approaching those observed in vivo. The ability of such laser-ablated microchannels to direct cell seeding was evaluated. The dimensions chosen were 100 μm wide, 100 μm deep and 10 mm long. Femtosecond laser ablation successfully produced these microchannels in the scaffolds without substantially altering the ~900 nm diameter fibers. Flow within these microchannels was studied by injecting fluorescent polystyrene bead solutions. Direct measurement of bead motion yielded an inlet velocity of 2.78 cm s(-1). This was used for modeling two-dimensional (2D) flow using computational fluid dynamics to estimate flow profiles within the microchannel. Successful demonstrations of bead flow were followed by seeding of 500,000 human coronary artery smooth muscle cells (HCASMCs) in proliferative medium at a rate of ~500 μL min(-1). Confocal microscopy and scanning electron microscopy confirmed that the HCASMCs were seeded down the full 10-mm length of the microchannel and stayed within its boundaries. Both nuclei and F-actin were observed within the seeded cells. The presence of F-actin filaments shows that the cells were adhered strongly to the scaffold and remained viable throughout the culture. The concept of "vascular wall engineering" producing intricate cell seeding through microchannels produced via femtosecond laser ablation was validated.

Modulation of mast cell adhesion, proliferation, and cytokine secretion on electrospun bioresorbable vascular grafts

Mast cells synthesize several potent angiogenic factors and can also stimulate fibroblasts, endothelial cells, and macrophages. An understanding of how they participate in wound healing and angiogenesis is important to further our knowledge about in situ vascular prosthetic regeneration. The adhesion, proliferation, and cytokine secretion of bone marrow-derived murine mast cells (BMMC) on electrospun polydioxanone, polycaprolactone, and silk scaffolds, as well as tissue culture plastic, has been investigated in the presence or absence of IL-3, stem cell factor, IgE and IgE with a crosslinking antigen, dinitrophenol-conjugated albumin (DNP). It was previously believed that only activated BMMCs exhibit adhesion and cytokine secretion. However, this study shows nonactivated BMMC adhesion to electrospun scaffolds. Silk scaffold was not found to be conducive for mast cell adhesion and cytokine secretion. Activation by IgE and DNP significantly enhanced mast cell adhesion, proliferation, migration, and secretion of tumor necrosis factor alpha, macrophage inflammatory protein-1α, and IL-13. This indicates that mast cells might play a role in the process of biomaterial integration into the host tissue, regeneration, and possibly angiogenesis.