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1.
Ramay HR  Zhang M 《Biomaterials》2004,25(21):5171-5180
A novel biodegradable nanocomposite porous scaffold comprising a beta-tricalcium phosphate (beta-TCP) matrix and hydroxyl apatite (HA) nanofibers was developed and studied for load-bearing bone tissue engineering. HA nanofibers were prepared with a biomimetic precipitation method. The composite scaffolds were fabricated by a method combining the gel casting and polymer sponge techniques. The role of HA nanofibers in enhancing the mechanical properties of the scaffold was investigated. Compression tests were performed to measure the compressive strength, modulus and toughness of the porous scaffolds. The identification and morphology of HA nanofibers were determined by X-ray diffraction and transmission electron microscopy, respectively. Scanning electron microscopy was used to examine the morphology of porous scaffolds and fracture surfaces to reveal the dominant toughening mechanisms. The results showed that the mechanical property of the scaffold was significantly enhanced by the inclusion of HA nanofibers. The porous composite scaffold attained a compressive strength of 9.8 +/- 0.3 MPa, comparable to the high-end value (2-10 MPa) of cancellous bone. The toughness of the scaffold increased from 1.00+/-0.04 to 1.72+/-0.02 kN/m, as the concentration of HA nanofibers increased from 0 to 5 wt %.  相似文献   

2.
In vivo biocompatibility and mechanical properties of porous zein scaffolds   总被引:3,自引:0,他引:3  
Wang HJ  Gong SJ  Lin ZX  Fu JX  Xue ST  Huang JC  Wang JY 《Biomaterials》2007,28(27):3952-3964
In our previous study, a three-dimensional zein porous scaffold with a compressive Young's modulus of up to 86.6+/-19.9 MPa and a compressive strength of up to 11.8+/-1.7 MPa was prepared, and was suitable for culture of mesenchymal stem cells (MSCs) in vitro. In this study, we examined its tissue compatibility in a rabbit subcutaneous implantation model; histological analysis revealed a good tissue response and degradability. To improve its mechanical property (especially the brittleness), the scaffolds were prepared using the club-shaped mannitol as the porogen, and stearic acid or oleic acid was added. The scaffolds obtained had an interconnected tubular pore structure, 100-380 microm in pore size, and about 80% porosity. The maximum values of the compressive strength and modulus, the tensile strength and modulus, and the flexural strength and modulus were obtained at the lowest porosity, reaching 51.81+/-8.70 and 563.8+/-23.4 MPa; 3.91+/-0.86 and 751.63+/-58.85 MPa; and 17.71+/-3.02 and 514.39+/-19.02 MPa, respectively. Addition of 15% stearic acid or 20% oleic acid did not affect the proliferation and osteogenic differentiation of MSCs, and a successful improvement of mechanical properties, especially the brittleness of the zein scaffold could be achieved.  相似文献   

3.
Gong S  Wang H  Sun Q  Xue ST  Wang JY 《Biomaterials》2006,27(20):3793-3799
A porous scaffold utilizing hydrophobic protein zein was prepared by the salt-leaching method for tissue engineering. The scaffolds possessed a total porosity of 75.3-79.0%, compressive Young's modulus of (28.2+/-6.7)MPa-(86.6+/-19.9)MPa and compressive strength of (2.5+/-1.2)MPa-(11.8+/-1.7)MPa, the percentage degradation of 36% using collagenase and 89% using pepsin during 14 days incubation in vitro. The morphology of pores located on the surface and within the porous scaffolds showed good pore interconnectivity by scanning electron microscopy (SEM). Rat mesebchymal stem cells (MSCs) could adhere, grow, proliferate and differentiate toward osteoblasts on porous zein scaffold. With the action of dexamethasone, the cells showed a relative higher activity of alkaline phosphatase (ALP) and a higher proliferating activity (p<0.05) than those of MSCs without dexamethasone.  相似文献   

4.
Biodegradable porous polymer scaffolds are widely used in tissue engineering to provide a structural template for cell seeding and extracellular matrix formation. Scaffolds must often possess sufficient structural integrity to temporarily withstand functional loading in vivo or cell traction forces in vitro. Both the mechanical and biological properties of porous scaffolds are determined in part by the local microarchitecture. Quantification of scaffold structure-function relationships is therefore critical for optimizing mechanical and biological performance. In this study, porous poly(L-lactide-co-DL-lactide) scaffolds with axially oriented macroporosity and random microporosity were produced using a solution coating and porogen decomposition method. Microarchitectural parameters were quantified as a function of porogen concentration using microcomputed tomography (micro-CT) analysis and related to compressive mechanical properties. With increasing porogen concentration, volume fraction decreased consistently due to microarchitectural changes in average strut thickness, spacing, and density. The three-dimensional interconnectivity of the scaffold porosity was greater than 99% for all porogen concentration levels tested. Over a porosity range of 58-80%, the average compressive modulus and ultimate strength of the scaffolds ranged from 43.5-168.3 MPa and 2.7-11.0 MPa, respectively. Thus, biodegradable porous polymer scaffolds have been produced with oriented microarchitectural features designed to facilitate vascular invasion and cellular attachment and with initial mechanical properties comparable to those of trabecular bone.  相似文献   

5.
To meet the challenge of regenerating bone lost to disease or trauma, biodegradable scaffolds are being investigated as a way to regenerate bone without the need for an auto- or allograft. Here, we have developed a novel microsphere-based chitosan/nanocrystalline calcium phosphate (CaP) composite scaffold and investigated its potential compared to plain chitosan scaffolds to be used as a bone graft substitute. Composite and chitosan scaffolds were prepared by fusing microspheres of 500-900 microm in diameter, and porosity, degradation, compressive strength, and cell growth were examined. Both scaffolds had porosities of 33-35% and pore sizes between 100 and 800 . However, composite scaffolds were much rougher and, as a result, had 20 times more surface area/unit mass than chitosan scaffolds. The compressive modulus of hydrated composite scaffolds was significantly higher than chitosan scaffolds (9.29 +/- 0.8 MPa vs. 3.26 +/- 2.5 MPa), and composite scaffolds were tougher and more flexible than what has been reported for other chitosan-CaP composites or CaP scaffolds alone. Using X-ray diffraction, scaffolds were shown to contain partially crystalline hydroxyapatite with a crystallinity of 16.7% +/- 6.8% and crystallite size of 128 +/- 55 nm. Fibronection adsorption was increased on composite scaffolds, and cell attachment was higher on composite scaffolds after 30 min, although attachment rates were similar after 1 h. Osteoblast proliferation (based on dsDNA measurements) was significantly increased after 1 week of culture. These studies have demonstrated that composite scaffolds have mechanical properties and porosity sufficient to support ingrowth of new bone tissue, and cell attachment and proliferation data indicate composite scaffolds are promising for bone regeneration.  相似文献   

6.
Biodegradable polymers and bioactive ceramics are being combined in a variety of composite materials for tissue engineering scaffolds. Materials and fabrication routes for three-dimensional (3D) scaffolds with interconnected high porosities suitable for bone tissue engineering are reviewed. Different polymer and ceramic compositions applied and their impact on biodegradability and bioactivity of the scaffolds are discussed, including in vitro and in vivo assessments. The mechanical properties of today's available porous scaffolds are analyzed in detail, revealing insufficient elastic stiffness and compressive strength compared to human bone. Further challenges in scaffold fabrication for tissue engineering such as biomolecules incorporation, surface functionalization and 3D scaffold characterization are discussed, giving possible solution strategies. Stem cell incorporation into scaffolds as a future trend is addressed shortly, highlighting the immense potential for creating next-generation synthetic/living composite biomaterials that feature high adaptiveness to the biological environment.  相似文献   

7.
Novel tissue engineering scaffold materials of nano-hydroxyapatite (nHA)/silk fibroin (SF) biocomposite were prepared by freeze-drying. The needle-like nHA crystals of about 10 nm in diameter by 50-80 nm in length, which were uniformly distributed in the porous nHA/SF scaffolds, were prepared by a co-precipitation method with a size. The as-prepared nHA/SF scaffolds showed good homogeneity, interconnected pores and high porosity. XRD and FT-IR analysis suggested that the silk fibroin was in beta-sheet structure, which usually provides outstanding mechanical properties for silk materials. In this work, composite scaffolds containing as high as 70% (w/w) nHA were prepared, which had excellent compressive modulus and strength, higher than the scaffolds at low nHA content level and other porous biodegradable polymeric scaffolds often considered in bone-related tissue engineering reported previously. The cell compatibility of composite scaffolds was evaluated through cell viability by MTT assay. All these results indicated that these nHA/SF scaffold materials may be a promising biomaterial for bone tissue engineering.  相似文献   

8.
A developmental composite scaffold for bone tissue engineering applications composed of hydroxyapatite (HA) and carboxymethylchitosan (CMC) was obtained using a coprecipitation method, which is based on the "autocatalytic" electroless deposition route. The results revealed that the pores of the scaffold were regular, interconnected, and possess a size in the range of 20-500 microm. Furthermore, the Fourier transform infra-red spectrum of the composite scaffolds exhibited all the characteristic peaks of apatite, and the appearance of typical bands from CMC, thus showing that coprecipitation of both organic and inorganic phases was effective. The X-ray diffraction pattern of composite scaffolds demonstrated that calcium-phosphates consisted of crystalline HA. From microcomputed tomography analysis, it was possible to determine that composite scaffolds possess a 58.9% +/- 6% of porosity. The 2D morphometric analysis demonstrated that on average the scaffolds consisted of 24% HA and 76% CMC. The mechanical properties were assessed using compressive tests, both in dry and wet states. Additionally, in vitro tests were carried out to evaluate the water-uptake capability, weight loss, and bioactive behavior of the composite scaffolds. The novel hydroxyapatite/carboxymethylchitosan composite scaffolds showed promise whenever degradability and bioactivity are simultaneously desired, as in the case of bone tissue-engineering scaffolding applications.  相似文献   

9.
A three-dimensional (3-D) scaffold is one of the major components in many tissue engineering approaches. We developed novel 3-D chitosan/poly(lactic acid-glycolic acid) (PLAGA) composite porous scaffolds by sintering together composite chitosan/PLAGA microspheres for bone tissue engineering applications. Pore sizes, pore volume, and mechanical properties of the scaffolds can be manipulated by controlling fabrication parameters, including sintering temperature and sintering time. The sintered microsphere scaffolds had a total pore volume between 28% and 37% with median pore size in the range 170-200microm. The compressive modulus and compressive strength of the scaffolds are in the range of trabecular bone making them suitable as scaffolds for load-bearing bone tissue engineering. In addition, MC3T3-E1 osteoblast-like cells proliferated well on the composite scaffolds as compared to PLAGA scaffolds. It was also shown that the presence of chitosan on microsphere surfaces increased the alkaline phosphatase activity of the cells cultured on the composite scaffolds and up-regulated gene expression of alkaline phosphatase, osteopontin, and bone sialoprotein.  相似文献   

10.
The photocross-linking of poly(propylene fumarate) (PPF) to form porous scaffolds for bone tissue engineering applications was investigated. PPF was cross-linked using the photoinitiator bis(2,4,6-trimethylbenzoyl) phenylphosphine oxide (BAPO) and exposure to 30 min of long wavelength ultraviolet (UV) light. The porous photocross-linked PPF scaffolds (6.5 mm diameter cylinders) were synthesized by including a NaCl porogen (70, 80, and 90 wt% at cross-linking) prior to photocross-linking. After UV exposure, the samples were placed in water to remove the soluble porogen, revealing the porous PPF scaffold. As porogen leaching has not been used often with cross-linked polymers, and even more rarely with photoinitiated cross-linking, a study of the efficacy of this strategy and the properties of the resulting material was required. Results show that the inclusion of a porogen does not significantly alter the photoinitiation process and the resulting scaffolds are homogeneously cross-linked throughout their diameter. It was also shown that porosity can be generally controlled by porogen content and that scaffolds synthesized with at least 80 wt% porogen possess an interconnected pore structure. Compressive mechanical testing showed scaffold strength to decrease with increasing porogen content. The strongest scaffolds with interconnected pores had an elastic modulus of 2.3+/-0.5 MPa and compressive strength at 1% yield of 0.11+/-0.02 MPa. This work has shown that a photocross-linking/porogen leaching technique is a viable method to form porous scaffolds from photoinitiated materials.  相似文献   

11.
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.  相似文献   

12.
Internal architecture has a direct impact on the mechanical and biological behaviors of porous hydroxyapatite (HA) implant. However, traditional processing methods provide minimal control in this regard. To address the issue, we developed a new processing method combining image-based design and solid free-form fabrication. We have previously published the processing method showing fabricated HA implants and their chemical properties. This study characterized the mechanical and the in vivo performance of designed HA implants. Thirteen HA implants with orthogonal channels at 40% porosity were tested on an Instron machine. The compressive strength and compressive modulus measured were 30+/-8 MPa and 1.4+/-0.4 GPa, comparable to coralline porous HA. Twenty-four cylindrical HA implants with two architecture designs, orthogonal and radial channels, were implanted in the mandibles of four Yucatan minipigs for 5 and 9 weeks. Normal bone regeneration occurred in both groups. At 9 weeks, bone penetrated 1.4mm into both scaffold designs. The percent bone ingrowth in the penetration zone was higher in the orthogonal channel design but not statistically different due to the low number of samples. However, the overall shape of the regenerated bone tissue was significantly different. In the orthogonal design, bone and HA formed an interpenetrating matrix, while in the radial design, the regenerated bone formed an intact piece at the center of the implant. These preliminary results showed that controlling the overall geometry of the regenerated bone tissue is possible through the internal architectural design of the scaffolds.  相似文献   

13.
Porous scaffolds of biphasic calcium phosphate (BCP)/polyamide 6 (PA6) with weight ratios of 30/70, 45/55, and 55/45 have been fabricated through a modified thermally induced phase separation technique. The chemical structure properties, macrostructure, and mechanical strength of the scaffolds were characterized by Fourier transform infrared spectroscopy, X-ray diffraction, thermogravimetric analysis, scanning electron microscopy, and mechanical testing. The results indicated that the BCP/PA6 scaffolds had an interconnected porous structure with a pore size mainly ranging from 100 to 900 μm and many micropores on the rough pore walls. The mechanical property of the scaffold was significantly enhanced by the addition of BCP inorganic fillers. The 55/45 BCP/PA6 composite scaffold with 76.5% ± 2.1% porosity attained a compressive strength of 1.86 ± 0.14 MPa. Moreover, the BCP/PA6 porous scaffold was cultured with rat calvarial osteoblasts to investigate the cell proliferation, viability, and differentiation function (alkaline phosphatase). The type I collagen expression was also used to characterize the differentiation of rat calvarial osteoblasts on BCP/PA6 composite scaffold by immunocytochemistry. The in vitro cytocompatibility evaluation demonstrated that the BCP/PA6 scaffold acted as a good template for the cells adhesion, spreading, growth, and differentiation. These results suggest that the BCP/PA6 porous composite could be a candidate as an excellent substitute for damaged or defect bone.  相似文献   

14.
In this study, highly porous collagen-HA scaffolds were prepared by solid-liquid phase separation method. Microstructure of the composites was characterized by SEM, TEM and XRD. The results show that collagen-HA scaffolds are porous with three-dimension interconnected fiber microstructure, pore sizes are 50-150 microm, and HA particles are dispersed evenly among collagen fiber. Compared with pure collagen, the mechanical property of collagen-HA composite improves significantly. To gain further insight into cell growth throughout 3D scaffolds, the cell proliferation and attachment on the scaffold in vitro was investigated. The collagen-HA composite has good biocompatibility, and adding HA does not affect the histocompatibility of the scaffold materials. The porous collagen-HA composite is suitable as scaffold used for bone tissue engineering.  相似文献   

15.
Novel tissue engineering scaffold materials of nano-hydroxyapatite (nHA)/silk fibroin (SF) biocomposite were prepared by freeze-drying. The needle-like nHA crystals of about 10 nm in diameter by 50–80 nm in length, which were uniformly distributed in the porous nHA/SF scaffolds, were prepared by a co-precipitation method with a size. The as-prepared nHA/SF scaffolds showed good homogeneity, interconnected pores and high porosity. XRD and FT-IR analysis suggested that the silk fibroin was in β-sheet structure, which usually provides outstanding mechanical properties for silk materials. In this work, composite scaffolds containing as high as 70% (w/w) nHA were prepared, which had excellent compressive modulus and strength, higher than the scaffolds at low nHA content level and other porous biodegradable polymeric scaffolds often considered in bone-related tissue engineering reported previously. The cell compatibility of composite scaffolds was evaluated through cell viability by MTT assay. All these results indicated that these nHA/SF scaffold materials may be a promising biomaterial for bone tissue engineering.  相似文献   

16.
In this study, composite scaffolds were prepared with polyethylene oxide (PEO)-linked gelatin and tricalcium phosphate (TCP). Chitosan, a positively charged polysaccharide, was introduced into the scaffolds to improve the properties of the artificial bone matrix. The chemical and thermal properties of composite scaffolds were investigated by Fourier transform infrared spectroscopy, thermogravimetric analyzer, differential thermal analyzer. In vitro cytotoxicity of the composite scaffold was also evaluated and the sample showed no cytotoxic effect. The morphology was studied by SEM and light microscopy. It was observed that the prepared scaffold had an open interconnected porous structure with pore size of 230-354 μm, which is suitable for osteoblast cell proliferation. The mechanical properties were assessed and it was found that the composite had compressive modulus of 1200 MPa with a strength of 5.2 MPa and bending modulus of 250 MPa having strength of 12.3 MPa. The porosity and apparent density were calculated and it was found that the incorporation of TCP can reduce the porosity and water absorption. It was revealed from the study that the composite had a 3D porous microstructure and TCP particles were dispersed evenly among the crosslinked gelatin/chitosan scaffold. ? 2012 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 100A:3020-3028, 2012.  相似文献   

17.
背景:以明胶为基体制备的组织工程支架材料具有良好的生物相容性和生物降解性能,但存在力学性能低,降解速率难以控制的缺陷。 目的:制备一种软骨组织工程支架材料多孔聚乙烯醇/明胶复合物,并检测其理化性能和生物相容性。 方法:采用乳化发泡法制备聚乙烯醇/明胶多孔支架,并通过电镜分析、力学测试、皮下植入实验,检测材料孔径和孔隙率、IR光谱、力学性能和生物相容性。 结果与结论:多孔材料内部呈三维网状多孔结构,孔径均匀,有相似的孔隙率61.8%,含水率44.6%,抗拉强度为(5.01±0.03) MPa,抗压强度为(1.47±0.36) MPa,有较好的力学性能,IR光谱分析表明材料内部结构均匀。皮下植入后,炎症反应逐渐减轻,囊壁逐渐变薄,并趋于稳定,提示多孔聚乙烯醇/明胶支架材料具有较好的生物相容性和力学性能。  相似文献   

18.
Novel three-dimensional scaffolds consisting of nano- and microsized hydroxyapatite (HA)/poly(epsilon-caprolactone) (PCL) composite were fabricated using a modified rapid-prototyping (RP) technique for bone tissue engineering applications. The size of the nano-HA ranged from 20 to 90 nm, whereas that of the micro-HA ranged from 20 to 80 microm. The scaffold macropores were well interconnected, with a porosity of 72-73% and a pore size of 500 microm. The compressive modulus of the nano-HA/PCL and micro-HA/PCL scaffolds was 3.187 +/- 0.06 and 1.345 +/- 0.05 MPa, respectively. The higher modulus of the nano-HA/PCL composite (n-HPC) was to be likely caused by a dispersion strengthening effect. The attachment and proliferation of MG-63 cells on n-HPC were better than that on the micro-HA/PCL composite (m-HPC) scaffold. The n-HPC was more hydrophilic than the m-HPC because of the greater surface area of HA exposed to the scaffold surface. This may give rise to better cell attachment and proliferation. Bioactive n-HA/PCL composite scaffold prepared using a modified RP technique has a potential application in bone tissue engineering.  相似文献   

19.
背景:目前组织工程骨修复骨缺损在临床应用中较为关键的问题是建立血管网,为新骨的形成提供氧气及营养物质,并为机体提供代谢途径。 目的:综述近年组织工程骨支架材料的特点,并着重介绍复合支架材料的研究现状。 方法:以“骨组织工程,血管化,支架材料,复合支架材料”为中文检索词,以“bone tissue engineering, vascularization,scaffold,composite scaffold”英文检索词,应用计算机在中国期刊全文数据库和PubMed数据库检索2001年1月至2014年1月的相关文章,将所有文章进行初步筛选后,对保留的文章进一步详细分析、归纳并总结。 结果与结论:按照组织工程骨支架材料的来源不同,可将其分为人工合成材料、天然衍生材料和复合支架材料,单一支架材料难以作为最理想的材料修复骨缺损,复合支架材料能在不同程度上弥补单一支架材料的缺陷,因此近年来组织工程支架材料的发展由单一材料发展为复合材料,并呈现人工合成材料与天然材料有机结合的趋势。但复合支架材料在临床应用中仍然有许多尚待解决的问题,主要有控制复合材料比例,使材料降解速率与组织细胞的生长速率相适应,保持复合材料的多孔隙和高机械强度。中国组织工程研究杂志出版内容重点:生物材料;骨生物材料; 口腔生物材料; 纳米材料; 缓释材料; 材料相容性;组织工程全文链接:  相似文献   

20.
J. Wang  X. Yu 《Acta biomaterialia》2010,6(8):3004-3012
In a previous study, a three-dimensional nanofibrous spiral scaffold for bone tissue engineering was developed, which showed enhanced human osteoblast cell attachment, proliferation and differentiation compared with traditional cylinder scaffolds, owing to the incorporation of spiral structures and nanofiber. However, the application of these scaffolds to bone tissue engineering was limited by their weak mechanical strength. This limitation triggered the design for novel structured scaffolds with reinforced physical characteristics. In this study, spiral polycaprolactone (PCL) nanofibrous scaffolds were inserted into poly(lactide-co-glycolide) (PLGA) microsphere sintered tubular scaffolds to form integrated scaffolds to provide mechanical properties and bioactivity appropriate for bone tissue engineering. Four experiment groups were designed: PLGA cylinder scaffold; PLGA tubular scaffold; PLGA tubular scaffold with PCL spiral structured inner core; PLGA tubular scaffold with PCL nanofiber containing spiral structured inner core. The morphology, porosity and mechanical properties of the scaffolds were characterized. Furthermore, human osteoblastic cells were seeded on these scaffolds, and the cell attachment, proliferation, differentiation and mineralized matrix deposition on the scaffolds were evaluated. The integrated scaffolds had Young’s modulus 250–300 MPa, and compressive strength 8–11 MPa under uniaxial compression. With the addition of an inner highly porous insert to the tubular shell, human osteoblast cells seeded on the integrated scaffolds showed slightly higher cell proliferation, 20–25% more alkaline phosphatase expression and twofold higher calcium deposition than those on the cylinder and tubular scaffolds. Furthermore, compared with sintered PLGA cylinder scaffolds, the integrated scaffolds allowed better cellular infiltration Therefore, this design demonstrates great potential for integrated scaffolds in bone tissue engineering applications.  相似文献   

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