PubMed Health⌕ Search

Biomedical subjects

Lichun Lu

Publications and source records attributed to Lichun Lu.

13 recordsLinked to original sources
PubMed2006

Controlled drug release from a novel injectable biodegradable microsphere/scaffold composite based on poly(propylene fumarate).

The ideal biomaterial for the repair of bone defects is expected to have good mechanical properties, be fabricated easily into a desired shape, support cell attachment, allow controlled release of bioactive factors to induce bone formation, and biodegrade into nontoxic products to permit natural bone formation and remodeling. The synthetic polymer poly(propylene fumarate) (PPF) holds great promise as such a biomaterial. In previous work we developed poly(DL-lactic-co-glycolic acid) (PLGA) and PPF microspheres for the controlled delivery of bioactive molecules. This study presents an approach to incorporate these microspheres into an injectable, porous PPF scaffold. Model drug Texas red dextran (TRD) was encapsulated into biodegradable PLGA and PPF microspheres at 2 microg/mg microsphere. Five porous composite formulations were fabricated via a gas foaming technique by combining the injectable PPF paste with the PLGA or PPF microspheres at 100 or 250 mg microsphere per composite formulation, or a control aqueous TRD solution (200 microg per composite). All scaffolds had an interconnected pore network with an average porosity of 64.8 +/- 3.6%. The presence of microspheres in the composite scaffolds was confirmed by scanning electron microscopy and confocal microscopy. The composite scaffolds exhibited a sustained release of the model drug for at least 28 days and had minimal burst release during the initial phase of release, as compared to drug release from microspheres alone. The compressive moduli of the scaffolds were between 2.4 and 26.2 MPa after fabrication, and between 14.9 and 62.8 MPa after 28 days in PBS. The scaffolds containing PPF microspheres exhibited a significantly higher initial compressive modulus than those containing PLGA microspheres. Increasing the amount of microspheres in the composites was found to significantly decrease the initial compressive modulus. The novel injectable PPF-based microsphere/scaffold composites developed in this study are promising to serve as vehicles for controlled drug delivery for bone tissue engineering.

Bone Cements↗
PubMed2006

Bone-tissue-engineering material poly(propylene fumarate): correlation between molecular weight, chain dimensions, and physical properties.

Poly(propylene fumarate) (PPF) is an important biodegradable and cross-linkable polymer designed for bone-tissue-engineering applications. For the first time we report the extensive characterization of this biomaterial including molecular weight dependences of physical properties such as glass transition temperature Tg, thermal degradation temperature Td, density rho, melt viscosity eta0, hydrodynamic radius RH, and intrinsic viscosity [eta]. The temperature dependence of eta0 changes progressively with molecular weight, whereas it can be unified when the temperature is normalized to Tg. The plateau modulus and entanglement molecular weight Me have been obtained from the rheological master curves. A variety of chain microstructure parameters such as the Mark-Houwink-Sakurada constants K and alpha, characteristic ratio Cinfinity, unperturbed chain dimension r0(2)/M, packing lengthp, Kuhn length b, and tube diameter a have been deduced. Further correlation between the microstructure and macroscopic physical properties has been discussed in light of recent progress in polymer dynamics to supply a better understanding about this unsaturated polyester to advance its biomedical uses. The molecular weight dependence of Tg for six polymer species including PPF has been summarized to support that Me is irrelevant for the finite length effect on the glass transition, whereas surprisingly these polymers can be divided into two groups when their normalized Tg is plotted simply against Mw to indicate the deciding roles of inherent chain properties such as chain fragility, intermolecular cooperativity, and chain end mobility.

Bone Substitutes↗
PubMed2005

Optimal segmentation of microcomputed tomographic images of porous tissue-engineering scaffolds.

The morphometric properties of the porous tissue-engineering scaffolds play a dominant role in the initial cell attachment and subsequent tissue regeneration. These properties can be derived nondestructively with the use of quantitative analysis of high-resolution microcomputed tomography (microCT) imaging of scaffolds. Accurate segmentation of these acquired images into solid and porous subspaces is critical to the integrity of morphometric analysis. The absence of a single image-processing technique to provide such accurate separability immune to all the intricacies of the acquired data makes this seemingly simple task significantly error prone. Consequently, an optimal segmentation has to be selected by ranking the segmentations produced by a multiplicity of methods. This article proposes a robust, easy-to-implement, unambiguous, signal-processing-based, ground-truth-free, segmentation rating metric that correlates with visual acuity. With the use of this metric it is possible, for the first time, to threshold the data with a wide range of techniques and select automatically the technique that best delineates the acquired image. The proposed solution has been extensively tested on microCT images of scaffolds fabricated with biodegradable poly (propylene fumarate) (PPF) with the use of a solvent casting particulate leaching process. The approaches proposed and the results obtained may have profound implications for accurate image-based characterization of tissue-engineering scaffolds.

Biocompatible Materials↗
PubMed2005

Multiple-channel scaffolds to promote spinal cord axon regeneration.

As molecular, cellular, and tissue-level treatments for spinal cord injury are discovered, it is likely that combinations of such treatments will be necessary to elicit functional recovery in animal models or patients. We describe multiple-channel, biodegradable scaffolds that serve as the basis for a model to investigate simultaneously the effects on axon regeneration of scaffold architecture, transplanted cells, and locally delivered molecular agents. Poly(lactic-co-glycolic acid) (PLGA) with copolymer ratio 85:15 was used for these initial experiments. Injection molding with rapid solvent evaporation resulted in scaffolds with a plurality of distinct channels running parallel along the length of the scaffolds. The feasibility of creating scaffolds with various channel sizes and geometries was demonstrated. Walls separating open channels were found to possess void fractions as high as 89%, with accessible void fractions as high as 90% through connections 220 microm or larger. Scaffolds degraded in vitro over a period of 30 weeks, over which time-sustained delivery of a surrogate drug was observed for 12 weeks. Primary neonatal Schwann cells were distributed in the channels of the scaffold and remained viable in tissue culture for at least 48 h. Schwann-cell containing scaffolds implanted into transected adult rat spinal cords contained regenerating axons at one month post-operation. Axon regeneration was demonstrated by three-dimensional reconstruction of serial histological sections.

Absorbable Implants↗
PubMed2005

Synthesis and characterizations of biodegradable and crosslinkable poly(epsilon-caprolactone fumarate), poly(ethylene glycol fumarate), and their amphiphilic copolymer.

A series of self-crosslinkable and biodegradable polymers, poly(caprolactone fumarate) (PCLF), poly(ethylene glycol fumarate) (PEGF), and their copolymer PEGF-co-PCLF, has been developed for tissue engineering applications using a novel synthesis method. The current method employs potassium carbonate (K2CO3), other than the previously reported triethylamine, as the proton scavenger. The new synthetic route is more convenient and less time-consuming to carry out, and the synthesized polymers have a much lighter color, which renders them more suitable for self-crosslinking via photo-initiation. This group of polymers are essentially copolymers of fumaryl chloride, which contains double bonds for in situ crosslinking, with poly(epsilon-caprolactone) (PCL) or/and poly(ethylene glycol) (PEG) that has a flexible chain to facilitate self-crosslinking. Both PCLF and PEGF, and their amphiphilic copolymer PEGF-co-PCLF could be self-crosslinked or photocrosslinked to produce scaffolds without the use of a crosslinking agent. Our results suggest that these polymers are potentially useful as injectable, self-crosslinkable, and photo-crosslinkable materials for diverse tissue engineering applications.

Biocompatible Materials↗
PubMed2004

Quantitative analysis of interconnectivity of porous biodegradable scaffolds with micro-computed tomography.

Pore interconnectivity within scaffolds is an important parameter influencing cell migration and tissue ingrowth needed to promote tissue regeneration. Methods for assessment of interconnectivity are usually qualitative, restricted to two-dimensional images, or are destructive. Microcomputed tomography nondestructively provides three-dimensional (3D) images of intact specimens at high spatial resolutions. We describe an image analysis technique for quantitative assessment of scaffold interconnectivity. Scaffolds were made via a particulate leaching process with 75%, 80%, 85%, and 88% volumetric porogen fractions. Specimens were scanned and resulting 3D, digital images were analyzed with a custom algorithm. A series of virtual, idealized scaffolds were also created for illustration of the algorithm's analysis approach and for its validation. The program calculated accessible void fractions over a range of minimum connection sizes. In real specimens, nearly 100% of the porous volume was connected with outside air for connections greater than or equal to 20 microm in their smallest dimension. In scaffolds made with 75% porogen, the accessible void fraction decreased to 78% if only those connections greater than or equal to 260 microm were considered. The relationship between accessible void fraction and connection size varied as a function of porogen content. The interconnectivity parameter described here may have implications for cell migration and tissue growth into scaffolds.

Algorithms↗
PubMed2004

Development of biodegradable poly(propylene fumarate)/poly(lactic-co-glycolic acid) blend microspheres. I. Preparation and characterization.

We developed poly(propylene fumarate)/poly(lactic-co-glycolic acid) (PPF/PLGA) blend microspheres and investigated the effects of various processing parameters on the characteristics of these microspheres. The advantage of these blend microspheres is that the carbon-carbon double bonds along the PPF backbone could be used for their immobilization in a PPF scaffold. Microspheres containing the model drug Texas red dextran were fabricated using a double emulsion-solvent extraction technique. The effects of the following six processing parameters on the microsphere characteristics were investigated: PPF/PLGA ratio, polymer viscosity, vortex speed during emulsification, amount of internal aqueous phase, use of poly(vinyl alcohol) (PVA) in the internal aqueous phase, and PVA concentration in the external aqueous phase. Our results showed that the microsphere surface morphology was affected most by the viscosity of the polymer solution. Microspheres fabricated with a kinematic viscosity of 39 centistokes had a smooth, nonporous surface. In most microsphere formulations, the model drug was dispersed uniformly in the polymer matrix. For all fabricated formulations, the average microsphere diameter ranged between 19.0 and 76.9 microm. The external PVA concentration and vortex speed had most effect on the size distribution. Entrapment efficiencies varied from 60 to 98% and were most affected by the amount of internal aqueous phase, vortex speed, and polymer viscosity. Overall, we demonstrated the ability to fabricate PPF/PLGA blend microspheres with similar surface morphology, entrapment efficiency, and size distribution as conventional PLGA microspheres.

Biocompatible Materials↗
PubMed2004

Development of biodegradable poly(propylene fumarate)/poly(lactic-co-glycolic acid) blend microspheres. II. Controlled drug release and microsphere degradation.

This article describes the effects of six processing parameters on the release kinetics of a model drug Texas red dextran (TRD) from poly(propylene fumarate)/poly(lactic-co-glycolic acid) (PPF/PLGA) blend microspheres as well as the degradation of these microspheres. The microspheres were fabricated using a double emulsion-solvent extraction technique in which the following six parameters were varied: PPF/PLGA ratio, polymer viscosity, vortex speed during emulsification, amount of internal aqueous phase, use of poly(vinyl alcohol) in the internal aqueous phase, and poly(vinyl alcohol) concentration in the external aqueous phase. We have previously characterized these microspheres in terms of microsphere morphology, size distribution, and TRD entrapment efficiency. In this work, the TRD release profiles in phosphate-buffered saline were determined and all formulations showed an initial burst release in the first 2 days followed by a decreased sustained release over a 38-day period. The initial burst release varied from 5.1 (+/-1.1) to 67.7 (+/-3.4)% of the entrapped TRD, and was affected most by the viscosity of the polymer solution used for microsphere fabrication. The sustained release between day 2 and day 38 ranged from 7.9 (+/-0.8) to 27.2 (+/-3.1)% of the entrapped TRD. During 11 weeks of in vitro degradation, the mass of the microspheres remained relatively constant for the first 3 weeks after which it decreased dramatically, whereas the molecular weight of the polymers decreased immediately upon placement in phosphate-buffered saline. Increasing the PPF content in the PPF/PLGA blend resulted in slower microsphere degradation. Overall, this study provides further understanding of the effects of various processing parameters on the release kinetics from PPF/PLGA blend microspheres thus allowing modulation of drug release to achieve a wide spectrum of release profiles.

Biocompatible Materials↗
PubMed2002

Bioactive poly(L-lactic acid) conduits seeded with Schwann cells for peripheral nerve regeneration.

This study attempted to enhance the efficacy of peripheral nerve regeneration using our previously tested poly(L-lactic acid) (PLLA) conduits by incorporating them with allogeneic Schwann cells (SCs). The SCs were harvested, cultured to obtain confluent monolayers and two concentrations (1 x 10(4) and 1 x 10(6) SC/ml) were combined with a collagen matrix (Vitrogen) and injected into the PLLA conduits. The conduits were then implanted into a 12 mm right sciatic nerve defect in rats. Three control groups were used: isografts, PLLA conduits filled with collagen alone and empty silicone tubes. The sciatic functional index (SFI) was calculated monthly through four months. At the end of second and fourth months, the gastrocnemius muscle was harvested and weighed for comparison and the graft conduit and distal nerve were harvested for histomorphologic analysis. The mean SFI demonstrated no group differences from isograft control. By four months, there was no significant difference in gastrocnemius muscle weight between the experimental groups compared to isograft controls. At four months, the distal nerve demonstrated a statistically lower number of axons mm2 for the high and low SC density groups and collagen control. The nerve fiber density was significantly lower in all of the groups compared to isograft controls by four months. The development of a "bioactive" nerve conduit using tissue engineering to replace autogenous nerve grafts offers a potential approach to improved patient care. Although equivalent nerve regeneration to autografts was not achieved, this study provides promising results for further investigation.

Animals↗
PubMed2002

Controlled release of NFkappaB decoy oligonucleotides from biodegradable polymer microparticles.

The objective of this study was to evaluate a poly(DL-lactic-co-glycolic acid)/poly(ethylene glycol) (PLGA/PEG) delivery system for nuclear factor-kappa B (NFkappaB) decoy phosphorothioated oligonucleotides (ODNs). PLGA/PEG microparticles loaded with ODNs were fabricated with entrapment efficiencies up to 70%. The effects of PEG contents (0, 5, and l0 wt%), ODN loading densities (0.4, 4, and 40 microg/mg), and pH of the incubation medium (pH 5, 7.4. and 10) on ODN release kinetics from the PLGA/PEG microparticles were investigated in vitro for up to 28 days. The release profiles in pH 7.4 phosphate buffered saline (PBS) were characterized by an initial burst during the first 2 days, a linear release phase until day 18, and a final release phase for the rest of the period. Up to 85% of the ODNs were released after 28 days in pH 7.4 PBS regardless of the ODN loading density and PEG content. Higher ODN loading densities resulted in lower entrapment efficiencies and greater initial burst effects. The bulk degradation of PLGA was not significantly affected by the PEG content and ODN loading density, but significantly accelerated at acidic buffer pH. Under acidic and basic conditions, the aggregation of microparticles resulted in significantly lower cumulative mass of released ODNs than that released at neutral pH. The effects of pH were reduced by the incorporation of PEG into PLGA microparticles. Since the PLGA degradation products are acidic, PLGA/PEG microparticles might provide a better ODN delivery vehicle than PLGA microparticles. These results suggest that PLGA/PEG microparticles are useful as delivery vehicles for controlled release of ODNs and merit further investigation in cell culture and animal models of glioblastoma.

Biocompatible Materials↗
PubMed2002

Effects of NFkappaB decoy oligonucleotides released from biodegradable polymer microparticles on a glioblastoma cell line.

The objectives of this study were to investigate a nuclear factor-kappa B (NFkappaB) decoy oligonucleotide (ODN) strategy on the inhibition of glioblastoma (GBM) cell line growth and to evaluate a poly(DL-lactic-co-glycolic acid) (PLGA) microparticle delivery system for the NFKB decoy ODNs in vitro. We have demonstrated that NFkappaB activation is important in regulating GBM cell line growth. Aberrant nuclear expression of NFkappaB was found in a panel of GBM cell lines, while untransformed glial cells did not display NFkappaB activity. Nuclear translocation of NFkappaB was inhibited by using a 'decoy" ODN strategy. NFkappaB decoy ODNs designed to inhibit NFkappaB resulted in a significant reduction in cell number (up to 45%) compared to control cultures after 2 days. The reduction in cell number correlated with a decrease in cyclin D1 protein expression and a commensurate decrease in Cdk-4 activity. These results provide evidence suggesting that NFkappaB mediates cell cycle progression and demonstrates a mechanism linking increased NFkappaB activity with GBM cell growth and cell cycle disregulation. Decoy ODNs were encapsulated at a yield of 66% in PLGA microparticles and released in a controlled manner in phosphate buffered saline for up to 28 days. Approximately 83% of entrapped ODNs were released by day 28. During 3 days of GBM cell line culture, the released decoy ODNs retained their biologic activity and led to significantly reduced cell number as compared to control cultures. These findings offer a potential therapeutic strategy in the control of human GBM cell line growth in vitro and suggest that PLGA microparticles may be appropriate as delivery vehicles for the "decoy" ODN strategy.

Active Transport, Cell Nucleus↗
PubMedDate not supplied

Synthesis, material properties, and biocompatibility of a novel self-cross-linkable poly(caprolactone fumarate) as an injectable tissue engineering scaffold.

A novel self-cross-linkable and biodegradable macromer, poly(caprolactone fumarate) (PCLF), has been developed for guided bone regeneration. This macromer is a copolymer of fumaryl chloride, which contains double bonds for in-situ cross-linking, and poly(epsilon-caprolactone), which has a flexible chain to facilitate self-cross-linkability. PCLF was characterized with Fourier transform infrared spectroscopy, 1H and 13C nuclear magnetic resonance spectroscopy, and gel permeation chromatography. Porous scaffolds were fabricated with sodium chloride particles as the porogen and a chemical initiation system. The PCLF scaffolds were characterized with scanning electron microscopy and micro-computed-tomography. The cytotoxicity and in vivo biocompatibility of PCLF were also assessed. Our results suggest that this novel copolymer, PCLF, is an injectable, self-cross-linkable, and biocompatible macromer that may be potentially used as a scaffold for tissue engineering applications.

Animals↗