Poly(lactide-co-glycolide)/hydroxyapatite nanofibrous scaffolds fabricated by electrospinning for bone tissue engineering

Poly(lactide-co-glycolide) (PLGA) nanofibrous composite scaffolds having nano-hydroxyapatite particles (HAp) in the fibers were prepared by electrospinning of PLGA and HAp with an average diameter of 266.6 ± 7.3 nm. Microscopy and spectroscopy characterizations confirmed integration of the crystalline HAp in the scaffolds. Agglomerates gradually appeared and increased on the fiber surface along with increase of the HAp concentration. In vitro mineralization in a 5 × simulated body fluid (SBF) revealed that the PLGA/HAp nanofibrous scaffolds had a stronger biomineralization ability than the control PLGA scaffolds. Biological performance of the nanofibrous scaffolds of the control PLGA and PLGA with 5 wt% HAp (PLGA/5HAp) was assessed by in vitro culture of neonatal mouse calvaria-derived MC3T3-E1 osteoblasts. Both types of the scaffolds could support cell proliferation and showed sharp increase of viability until 7 days, but the cells cultured on the PLGA/5HAp nanofibers showed a more spreading morphology. Despite the similar level of the cell viability and cell number at each time interval, the alkaline phosphatase secretion was significantly enhanced on the PLGA/5HAp scaffolds, indicating the higher bioactivity of the as-prepared nano-HAp and the success of the present method for preparing biomimetic scaffold for bone regeneration.     

Basic research on aw-AC/PLGA composite scaffolds for bone tissue engineering

Recently, it has become important to develop effective material to be used as scaffolds for bone tissue engineering. Therefore, we fabricated new three-dimensional (3D) scaffolds consisting of biodegradable poly(d,l-lactide-co-glycolic acid)(PLGA)(75/25) with anti-washout type AC (aw-AC) particles. The aim of this study was to evaluate this new scaffold concerning its basic properties and biocompatibility. The obtained scaffolds were observed with scanning electron microscopy (SEM), and measured for porosity, shrinkage and biaxial compressive strengths. It was shown that PLGA with aw-AC composite scaffolds (aw-AC/PL) showed a greater strength and stability than PLGA scaffolds (PL). Also, the mass reduction of aw-AC/PL during incubation decreased compared to that of PL. The number of MC3T3-E1 cell in PL and aw-AC/PL was counted at 5 h, 1 week, and 2 weeks after cell seeding. As a result, aw-AC/PL exhibited a superior performance in terms of attachment and proliferation compared to PL. Histologically, aw-AC/PL showed an excellent response toward soft tissues. Therefore, it was shown that aw-AC/PL was more biocompatible than PL. In conclusion, it was strongly suggested that aw-AC/PL was more useful for cell transplantation than PL in bone tissue engineering.     

5-Fluorouracil encapsulated HA/PLGA composite microspheres for cancer therapy

5-Fluorouracil (5FU) was successfully entrapped within poly(lactide-co-glycolide) (PLGA) and hydroyapatite (HA) composite microspheres using the emulsification/solvent extraction technique. The effects of HA to PLGA ratio, solvent ratio as well as polymer inherent viscosity (IV) on encapsulation efficiency were investigated. The degradation and drug release rates of the microspheres were studied for 5?weeks in vitro in phosphate buffered solution of pH 7.4 at 37?°C. The drug release profile followed a biphasic pattern with a small initial burst followed by a zero-order release for up to 35?days. The initial burst release decreased with increasing HA content. The potential of HA in limiting the initial burst release makes the incorporation of HA into PLGA microspheres advantageous since it reduces the risk of drug overdose from high initial bursts. The linear sustained drug release profile over the course of 5?weeks makes these 5-FU-loaded HA/PLGA composite microparticles a promising delivery system for the controlled release of chemotherapy drugs in the treatment of cancer.     

Fabrication and evaluation of a sustained-release chitosan-based scaffold embedded with PLGA microspheres

Nutrient depletion within three-dimensional (3D) scaffolds is one of the major hurdles in the use of this technology to grow cells for applications in tissue engineering. In order to help in addressing it, we herein propose to use the controlled release of encapsulated nutrients within polymer microspheres into chitosan-based 3D scaffolds, wherein the microspheres are embedded. This method has allowed maintaining a stable concentration of nutrients within the scaffolds over the long term. The polymer microspheres were prepared using multiple emulsions (w/o/w), in which bovine serum albumin (BSA) and poly (lactic-co-glycolic) acid (PLGA) were regarded as the protein pattern and the exoperidium material, respectively. These were then mixed with a chitosan solution in order to form the scaffolds by cryo-desiccation. The release of BSA, entrapped within the embedded microspheres, was monitored with time using a BCA kit. The morphology and structure of the PLGA microspheres containing BSA before and after embedding within the scaffold were observed under a scanning electron microscope (SEM). These had a round shape with diameters in the range of 27–55 μm, whereas the chitosan-based scaffolds had a uniform porous structure with the microspheres uniformly dispersed within their 3D structure and without any morphological change. In addition, the porosity, water absorption and degradation rate at 37 °C in an aqueous environment of 1% chitosan-based scaffolds were (92.99 ± 2.51) %, (89.66 ± 0.66) % and (73.77 ± 3.21) %, respectively. The studies of BSA release from the embedded microspheres have shown a sustained and cumulative tendency with little initial burst, with (20.24 ± 0.83) % of the initial amount released after 168 h (an average rate of 0.12%/h). The protein concentration within the chitosan-based scaffolds after 168 h was found to be (11.44 ± 1.81) × 10^? 2 mg/mL. This novel chitosan-based scaffold embedded with PLGA microspheres has proven to be a promising technique for the development of new and improved tissue engineering scaffolds.     

In vivo evaluation of composites of PLGA and apatite with two different levels of crystallinity

The cortical bone response towards poly(lactide-co-glycolide) (70/30) (PLGA) (70/30)/apatite complex scaffolds with different levels of crystallinity was investigated. Apatite with different levels of crystallinity, Ca-deficient hydroxyapatite (CDHA), which has a low crystallinity, and a mixture of carbonated hydroxyapatite (CHA) and CDHA, which has a higher crystallinity, were prepared from an aqueous mixture of Ca-EDTA complex, H₂O₂, H₃PO₄, and NH₄OH. Two porous PLGA(70/30)/apatite composite scaffolds, composite scaffold A (containing low crystallinity CDHA) and composite scaffold B (containing the higher crystallinity CHA/CDHA mixture), were prepared. Afterwards, pure porous PLGA and the two composite scaffolds were implanted into the cortical bone of rabbit tibiae for 12 weeks. High-resolution microfocus X-ray computed tomography and histological examinations revealed a better bone response for composite scaffold A compared with PLGA and composite scaffold B. For composite scaffold A, the original bone defect was almost filled with new bone. Quantitative analysis revealed that composite scaffold A produced a significantly greater amount of new bone. The present study demonstrated that the level of apatite crystallinity influences bone response. A PLGA/apatite porous composite with a low level of apatite crystallinity shows promise as a bone substitute or scaffold material for bone tissue engineering.     

可缓释药物的明胶/磷酸钙骨水泥复合组织工程支架材料

采用向孔隙中灌注含聚乳酸聚乙醇酸共聚物（PLGA）载药微球的明胶溶液的方法制备了具有药物缓释功能的明胶/磷酸钙骨水泥复合组织工程支架。用扫描电子显微镜观察了微球和支架的形貌特征,用万能材料试验机测定了支架材料的抗压强度,用紫外-可见分光光度计分析了复合支架的释药率。结果表明,灌注明胶对多孔磷酸钙骨水泥支架起到显著的增强作用,抗压强度达2.42 MPa。复合支架携载硫酸庆大霉素, 具有良好的药物缓释功能,缓释时间可达30天以上,使支架在修复骨缺损的同时能消除炎症反应,成为一种集骨修复和治疗于一体的新型组织工程支架材料,具有良好的应用前景。      

Preparation and property of a novel bone graft composite consisting of rhBMP-2 loaded PLGA microspheres and calcium phosphate cement

Calcium phosphate cement (CPC) is a highly promising bone substitute and an excellent carrier for delivering growth factors. Yet, the lack of macro-porosity and osteoinductive ability, limit its use. This study is aimed at developing a novel biodegradable biomaterial for bone repair with both highly osteoconductive and osteoinductive properties. RhBMP-2 loaded PLGA microspheres were incorporated into rhBMP-2/CPC for macropores for bone ingrowth. The compressive strength, crystallinity, microscopic structure, and bioactivity of the composites were investigated. The results showed that with the incorporation of rhBMP-2 loaded PLGA microspheres, the compressive strength was decreased from (29.48 ± 6.42) MPa to (8.26 ± 3.58) MPa. X-ray diffraction revealed that the crystallinity pattern of HA formed by CPC had no significant change. Inside the composite, the microspheres distributed homogeneously and contacted intimately with the HA matrix, as observed by scanning electron microscopy (SEM). When the PLGA microspheres dissolved after having been emerged in PBS for 56 days, macropores were created within the CPC. The rhBMP-2/PLGA/CPC composite, showing a 4.9% initial release of rhBMP-2 in 24 h, followed by a prolonged release for 28 days, should have a greater amount of rhBMP-2 released compared to the CPC delivery system. When rabbit marrow stromal cells were cocultured with the composite, the alkaline phosphatase (ALP) and osteocalcin (OC) showed a dose response to the rhBMP-2 released from the composite, indicating that the activity of rhBMP-2 was retained. This study shows that the new composite reveals more rhBMP-2 release and osteogenic activity. This novel BMP/PLGA/CPC composite could be a promising synthetic bone graft in craniofacial and orthopedic repairs.     

Fabrication of mineralized electrospun PLGA and PLGA/gelatin nanofibers and their potential in bone tissue engineering

Surface mineralization is an effective method to produce calcium phosphate apatite coating on the surface of bone tissue scaffold which could create an osteophilic environment similar to the natural extracellular matrix for bone cells. In this study, we prepared mineralized poly(d,l-lactide-co-glycolide) (PLGA) and PLGA/gelatin electrospun nanofibers via depositing calcium phosphate apatite coating on the surface of these nanofibers to fabricate bone tissue engineering scaffolds by concentrated simulated body fluid method, supersaturated calcification solution method and alternate soaking method. The apatite products were characterized by the scanning electron microscopy (SEM), Fourier transform-infrared spectroscopy (FT-IR), and X-ray diffractometry (XRD) methods. A large amount of calcium phosphate apatite composed of dicalcium phosphate dihydrate (DCPD), hydroxyapatite (HA) and octacalcium phosphate (OCP) was deposited on the surface of resulting nanofibers in short times via three mineralizing methods. A larger amount of calcium phosphate was deposited on the surface of PLGA/gelatin nanofibers rather than PLGA nanofibers because gelatin acted as nucleation center for the formation of calcium phosphate. The cell culture experiments revealed that the difference of morphology and components of calcium phosphate apatite did not show much influence on the cell adhesion, proliferation and activity.     

Electrospinning of PLGA/gelatin randomly-oriented and aligned nanofibers as potential scaffold in tissue engineering

Electrospinning technique can be used to produce the three-dimensional nanofibrous scaffold similar to natural extracellular matrix, which satisfies particular requirements of tissue engineering scaffold. Randomly-oriented and aligned poly(lactic-co-glycolic acid) (PLGA) and PLGA/gelatin biocomposite scaffolds were successfully produced by electrospinning in the present study. The resulting nanofibrous scaffolds exhibited smooth surface and high porous structure. Blending PLGA with gelatin enhanced the hydrophilicity but decreased the average fiber diameter and the mechanical properties of the scaffolds under the same electrospinning condition. The cell culture results showed that the elongation of the osteoblast on the aligned nanofibrous scaffold was parallel to the fiber arrangement and the cell number was similar to that of randomly-oriented scaffold, indicating that the aligned nanofibrous scaffold provide a beneficial approach for the bone regeneration.     

PLGA/TSF静电纺纳米纤维的仿生矿化及生物相容性

利用静电纺丝和模拟体液仿生矿化技术制备了聚乳酸-羟基乙酸共聚物/柞蚕丝素/羟基磷灰石((PLGA/TSF/HA)骨组织工程复合支架。通过扫描电子显微镜(SEM)、透射电子显微镜(TEM)、X射线衍射测试(XRD)和热重分析(TG)对复合纳米纤维的形貌结构进行了表征。此外,在复合纳米纤维支架材料上接种人骨髓间充质干细胞(hMSCs),通过四甲基偶氮噻唑蓝比色(Four methyl azo thiazole blue colorimetric,MTT)法,观察细胞在材料表面的生长情况评价纳米纤维的生物相容性。结果显示,PLGA/TSF纳米纤维毡具有精细的三维结构,纤维直径分布均匀,表面光滑。矿化后HA颗粒均匀地分布在PLGA/TSF纳米纤维表面,矿物含量约占63%。与PLGA/TSF纳米纤维支架相比,PLGA/TSF/HA纳米纤维支架的亲水性、生物相容性都得到显著提高。     

Fabrication and characterization of porous poly(lactic-<Emphasis Type="Italic">co</Emphasis>-glycolic acid) (PLGA) microspheres for use as a drug delivery system

In this work, Simvastatin (SIM) loaded porous poly(lactic-co-glycolic acid) (PLGA) microspheres were fabricated using the W/O/W1/W2 double emulsion and solvent evaporation method. The optimal conditions for fabricating porous PLGA microspheres were determined to be 20% distilled water (v/v), 10% PLGA (m/v), and a 4:1 ratio of internal polyvinyl alcohol (PVA) to dichloromethane (DCM). The pores size distribution of porous PLGA microspheres was varied from 0.01 to 40 μm, while their particle displayed a bimodal size distribution that had two diameter peaks at around 100 μm and 500 μm. The SIM encapsulation efficacy was found to be very high with a yield near 80% and the porous PLGA microspheres showed the excellent biocompatibility. In addition, the drug release profile was found to be significantly different from a temporal basis. Base on the combined results of this study, SIM loaded PLGA microspheres holds great promise for use in biomedical applications, especially in drug delivery system or tissue regeneration.     

Improvement in angiogenesis and osteogenesis with modified cannulated screws combined with VEGF/PLGA/fibrin glue in femoral neck fractures

Angiogenesis is essential for bone healing. Vascular endothelial growth factor (VEGF) is regarded as one of the most potent antigenic cytokines; however, there have been very few studies that have previously investigated the effects of VEGF on bone healing in a femoral neck fracture model. Thus, the aim of the present study was to test both the angiogenic and osteogenic properties of a VEGF/poly-lactic acid glycolic acid (PLGA) delivery system for the treatment of femoral neck fractures. VEGF/PLGA microspheres were prepared by the double emulsion solvent-evaporation method and in vitro VEGF release was quantified by an ELISA assay. Then the preparation of femoral neck fracture model and internal fixation were performed, and the effect of the VEGF/PLGA microspheres on bone healing was determined by X-ray, radionuclide bone scanning, and histomorphometric evaluation. The release of VEGF from the VEGF/PLGA microspheres was sustained for at least 42 days in vitro, and suspension of the delivery system in fibrin glue further slowed this VEGF release rate. In dogs, revascularization of the fractured femoral heads was significantly improved by a local injection of VEGF/PLGA/fibrin glue, and the quality and speed of fracture healing were significantly improved in the Experimental group than in the Control group. Our study confirmed that the VEGF/PLGA delivery system offers good angiogenic and osteogenic properties for the treatment of canine femoral neck fractures.     

Porous calcium phosphate ceramics modified with PLGA–bioactive glass

Porous calcium phosphate ceramics (mainly hydroxyapatite) with interconnected macropores (∼1 mm) and micropores (∼5 μm) as well as high porosities (∼80%) were prepared by firing polyurethane foams that were coated with calcium phosphate cement at 1200 °C. In order to improve the mechanical properties such as compressive strength and compressive modulus and maintain the desirable bioactivity (i.e. the ability of apatite layer formation), the open micropores of the struts were infiltrated with poly(lactic-co-glycolic acid) (PLGA) to achieve an interpenetrating bioactive ceramic/biodegradable polymer composite structure. The PLGA filled struts were further coated with a 58S bioactive glass (33 wt.%)–PLGA composite coating. The PLGA–bioactive glass modified porous calcium phosphate ceramics proved to be bioactive and exhibited compressive strengths up to 7.7 MPa and compressive moduli up to 3 GPa, which were comparable to those of natural spongy bones. The obtained complex porous bioactive/biodegradable composites could be used as tissue engineering scaffolds for low-load bearing applications.     

Evaluation of bone matrix and demineralized bone matrix incorporated PLGA matrices for bone repair

The aim of this study was to evaluate the composite matrices prepared using Poly(lactic-co-glycolic acid)- PLGA (85:15) by incorporating human bone matrix (BM) powder or demineralized bone matrix (DBM) powder with the weight ratio of polymer: BM or DBM (75:25) to apply for bone repair. Murine Bone Marrow Stromal Cell (BMSC) attachment was studied with different time points at 30 min, 1 h, 2 h, 4 h, and 6 h for BM/PLGA, DBM/PLGA and PLGA control matrices. All types of matrices were linearly increased the BMSC attachment with the increase of time. Significantly higher number of BMSCs was attached to the both BM/PLGA and DBM/PLGA matrices after 2 h compared to the controls. If BM or DBM is incorporated into biodegradable PLGA matrices and cultured with BMSCs, those composite matrices could be potentially used for bone tissue engineering applications. In addition, particle migration and handling difficulties in DBM powder in clinical applications eliminate using a PLGA matrix. Furthermore, we have observed that DBM/PLGA matrices were structurally stronger compared to the BM/PLGA or control PLGA matrices when they exposed to physiological environment for 72 days.     

Biomimetic mineralization of electrospun poly(lactic-co-glycolic acid)/multi-walled carbon nanotubes composite scaffolds in vitro

Biomimetic mineralization is an effective method to improve the biocompatibility and bone inductivity of certain materials. In this study, composite scaffolds composed of poly(lactic-co-glycolic acid) (PLGA) and multi-walled carbon nanotubes (MWNTs) were prepared by electrospinning. Subsequently, the scaffolds were immersed in a simulated body fluid (1.5 × SBF) at 37 °C for 7, 14 and 21 days for biomimetic mineralization. Scanning electron microscopy, Raman spectroscopy, and X-ray diffraction were used for characterization. It was found that the electrospun scaffolds had extremely resemblant structural morphology to the natural extracellular matrix. After mineralization, apatite crystals were deposited on the PLGA/MWNTs composite scaffolds. The mineralized PLGA/MWNTs composites may be potentially useful in tissue engineering applications, particularly as scaffolds for bone tissue regeneration.     

Subcritical CO2 sintering of microspheres of different polymeric materials to fabricate scaffolds for tissue engineering

The aim of this study was to use CO₂ at sub-critical pressures as a tool to sinter 3D, macroporous, microsphere-based scaffolds for bone and cartilage tissue engineering. Porous scaffolds composed of ~ 200 μm microspheres of either poly(lactic-co-glycolic acid) (PLGA) or polycaprolactone (PCL) were prepared using dense phase CO₂ sintering, which were seeded with rat bone marrow mesenchymal stromal cells (rBMSCs), and exposed to either osteogenic (PLGA, PCL) or chondrogenic (PLGA) conditions for 6 weeks. Under osteogenic conditions, the PLGA constructs produced over an order of magnitude more calcium than the PCL constructs, whereas the PCL constructs had far superior mechanical and structural integrity (125 times stiffer than PLGA constructs) at week 6, along with twice the cell content of the PLGA constructs. Chondrogenic cell performance was limited in PLGA constructs, perhaps as a result of the polymer degradation rate being too high. The current study represents the first long-term culture of CO₂-sintered microsphere-based scaffolds, and has established important thermodynamic differences in sintering between the selected formulations of PLGA and PCL, with the former requiring adjustment of pressure only, and the latter requiring the adjustment of both pressure and temperature. Based on more straightforward sintering conditions and more favorable cell performance, PLGA may be the material of choice for microspheres in a CO₂ sintering application, although a different PLGA formulation with the encapsulation of growth factors, extracellular matrix-derived nanoparticles, and/or buffers in the microspheres may be advantageous for achieving a more superior cell performance than observed here.     

In vivo investigation of ceftiofur-loaded gelatin and PLGA microspheres in beagle dogs

Drug delivery systems based on polymer microspheres have received considerable attention. Ceftiofur sodium and ceftiofur hydrochloride is widely used for the treatment of bacterial diseases in animals but the delivery in vivo has not been reported. In this paper, we report the synthesis of microspheres from gelatin and PLGA, two kinds of typical natural and artificial materials, for loading ceftiofur and the in vivo investigation of the pharmacokinetics in beagle dogs. By controlling the synthesis parameters, gelatin and PLGA microspheres with diameter between 5 and 35 microns were obtained. Assay procedures based on high performance liquid chromatography were evaluated and confirmed. The dogs were randomly divided into three groups, i.e., control group, gelatin group, and PLGA group and administrated via intravenous injection. Plasma concentrations of ceftiofur over time were measured and analyzed. Results indicate that the main kinetic parameters do not show significant difference for the gelatin group and control group, but the area under the curve, plasma half-life, apparent volume of distribution, and clearance ratio of PLGA group show significant difference from the gelatin group and the control group. The PLGA microspheres show a low area under the curve but long time release.     

Preparation and evaluation of a novel bioactive glass/lysozyme/PLGA composite microsphere

Objective: The objective of this study was to fabricate a novel nano-bioceramics incorporated lysozyme poly (d, l-lactide-co-glycolide) (PLGA) microsphere.

Methods: The nano-bioceramics was used as a biodegradable and sustained-release antacid to stabilize the lysozyme in the drug release process. First, the nano-bioceramics were prepared by sol-gel method, and then were characterized by energy dispersive X-ray analysis, dynamic light scattering and in vitro degradation test. Second, the lysozyme PLGA microsphere incorporated with nano-bioceramic was fabricated by the S/W/O/W emulsion solvent evaporation method. The microsphere was characterized by scanning electron microscopy (SEM), Fourier transform infrared (FTIR) spectroscopy and UV circular dichroism (UV CD). Finally the in vitro drug release and bioactivity test was carried out.

Results: The composition of the nano-bioceramics was 58% SiO₂, 36% CaO, 6% P₂O₅, and the average particle size was 295?nm. The nano-bioceramics incorporated lysozyme PLGA microspheres were prepared by the multi-emulsion method. The SEM results showed that the bioceramics was uniformly distributed in the PLGA microsphere. Results from in vitro lysozyme release test exhibited a prolonged release time for 1month. The FTIR and UVCD results suggested that the lysozyme in the drug release process had a similar secondary structure conformation to the native one. The Micrococcus lysodeikticus test showed that the microspheres incorporated with bioceramics provided long-term protein stability against the acidic environment resulted from PLGA’s degradates and more than 90% of the lysozyme released over the 1 month period was preserved in a bioactive form.

Conclusion: A novel bioceramics incorporated lysozyme PLGA microsphere was prepared with potentials for sustained protein release formulation.     

Bone induction by biomimetic PLGA copolymer loaded with a novel synthetic RADA16-P24 peptide in vivo

Bone morphogenetic protein-2 (BMP-2) is a key bone morphogenetic protein, and poly(lactic-co-glycolic acid) (PLGA) has been widely used as scaffold for clinical use to carry treatment protein. In the previous studies, we have synthesized BMP-2-related peptide (P24) and found its capacity of inducing bone regeneration. In this research, we have synthesized a new amphiphilic peptide Ac-RADA RADA RADA RADA S[PO4]KIPKASSVPTELSAISTLYLDDD-CONH2 (RADA16-P24) with an assembly peptide RADA16-Ion the P24 item of BMP2 to form divalent ion-induced gelatin. Two methods of physisorption and chemical cross-linking were used to bind RADA16-P24 onto the surface of the copolymer PLGA to synthesize RADA16-P24–PLGA, and its capacity of attaching bone marrow stromal cells (BMSCs) was evaluated in vitro and inducing ectopic bone formation was examined in vivo. In vitro our results demonstrated that RADA16-P24–PLGA copolymer prepared by physisorbing or prepared by chemical cross-linking had a peptide binding rate of (2.0180 ± 0.5296)% or (10.0820 ± 0.8405)% respectively (P < 0.05). In addition the BMSCs proliferated vigorously in the RADA16-P24–PLGA biomaterials. Significantly the percentage of BMSCs attached to RADA16-P24–PLGA composite prepared by chemical cross-linking and physisorbing were (71.4 ± 7.5) % or (46.7 ± 5.8) % (P < 0.05). The in vivo study showed that RADA16-P24–PLGA chemical cross-linking could better induce ectopic bone formation compared with RADA16-P24–PLGA physisorbing and PLGA. It is concluded that the PLGA copolymer is a good RADA16-P24 carrier. This novel RADA16-P24–PLGA composite has strong osteogenic capability.     

Degradation behavior of hydrophilized PLGA scaffolds prepared by melt-molding particulate-leaching method: Comparison with control hydrophobic one

Porous PLGA/PVA scaffolds as hydrophilized PLGA scaffolds for tissue engineering applications were fabricated by a novel melt-molding particulate leaching method (non-solvent method). The prepared scaffolds exhibited highly porous and open-cellular pore structures with almost same surface and interior porosities (pore size, 200–300 μ m; porosity, about 90%). The in vitro degradation behavior of the PLGA and PLGA/PVA scaffolds was compared at 37^∘C in PBS (pH 7.4) with and without the solution change everyday to see the effect of solution pH as well as scaffold hydrophilicity on the degradation behavior. The changes in dimension, molecular weight, mechanical properties (maximum load and modulus), and morphology of the scaffolds were examined with degradation time. The degradation behavior of the PLGA and PLGA/PVA scaffolds was further investigated in vivousing a rat model (subcutaneously implantation). It was observed that both PLGA and PLGA/PVA scaffolds in decreasing pH condition (PBS no change) showed faster degradation than those in constant pH condition (PBS change everyday), owing to the enhanced intramolecular depolymerization by the increment of chain hydrophilicity caused by carboxylate groups as well as the autocatalysis of carboxylic acids accumulated in the solution by the cleavage of PLGA backbone ester bonds. The scaffolds in vivo condition also showed faster degradation than those in vitro, probably due to the aid of foreign body giant cells or enzymes. The PLGA/PVA scaffold showed slightly faster degradation than the PLGA scaffold for both in vitro and in vivo conditions. Author to whom all correspondence should be addressed.