Tissue engineered microsphere-based matrices for bone repair:

Borden, Mark; Attawia, Mohamed; Khan, Yusuf; Laurencin, Cato T.

doi:10.1016/s0142-9612(01)00137-5

Cited by 259 publications

(195 citation statements)

References 22 publications

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“…A variety of matrix fabrication techniques including particulate leaching, [28] gas foaming, [29] phase separation, [30] and sphere sintering [31] have been developed to produce 3D porous matrices for skeletal tissue regeneration during the past two decades. It has been demonstrated that a porosity of ~90% is highly desirable for an ideal scaffold by providing sufficient space for extracellular matrix (ECM) synthesis, a high surface area for cell–material interactions, and minimal diffusion constraints.…”

Section: Discussionmentioning

confidence: 99%

“…The morphology of such in situ formed porous structure resembled our sintered microsphere matrix, which is a biomimetic 3D pore system resulted from fused polymer microspheres. [31] In particular, a sintered microsphere matrix from PLAGA has attracted significant interest as a load-bearing scaffold for orthopaedic tissue engineering. [23, 34] However, for large porous structures the use of a bioreactor might be essential for complete cell infiltration, because the preformed structures present nutrient and oxygen diffusion limitations.…”

Section: Discussionmentioning

confidence: 99%

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Porous Structures: In situ Porous Structures: A Unique Polymer Erosion Mechanism in Biodegradable Dipeptide‐Based Polyphosphazene and Polyester Blends Producing Matrices for Regenerative Engineering (Adv. Funct. Mater. 17/2010)

Deng

Nair

Nukavarapu

et al. 2010

Adv Funct Materials

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Synthetic biodegradable polymers serve as temporary substrates that accommodate cell infiltration and tissue in-growth in regenerative medicine. To allow tissue in-growth and nutrient transport, traditional three-dimensional (3D) scaffolds must be prefabricated with an interconnected porous structure. Here we demonstrated for the first time a unique polymer erosion process through which polymer matrices evolve from a solid coherent film to an assemblage of microspheres with an interconnected 3D porous structure. This polymer system was developed on the highly versatile platform of polyphosphazene-polyester blends. Co-substituting a polyphosphazene backbone with both hydrophilic glycylglycine dipeptide and hydrophobic 4-phenylphenoxy group generated a polymer with strong hydrogen bonding capacity. Rapid hydrolysis of the polyester component permitted the formation of 3D void space filled with self-assembled polyphosphazene spheres. Characterization of such self-assembled porous structures revealed macropores (10-100 μm) between spheres as well as micro- and nanopores on the sphere surface. A similar degradation pattern was confirmed in vivo using a rat subcutaneous implantation model. 12 weeks of implantation resulted in an interconnected porous structure with 82-87% porosity. Cell infiltration and collagen tissue in-growth between microspheres observed by histology confirmed the formation of an in situ 3D interconnected porous structure. It was determined that the in situ porous structure resulted from unique hydrogen bonding in the blend promoting a three-stage degradation mechanism. The robust tissue in-growth of this dynamic pore forming scaffold attests to the utility of this system as a new strategy in regenerative medicine for developing solid matrices that balance degradation with tissue formation.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Porous Structures: In situ Porous Structures: A Unique Polymer Erosion Mechanism in Biodegradable Dipeptide‐Based Polyphosphazene and Polyester Blends Producing Matrices for Regenerative Engineering (Adv. Funct. Mater. 17/2010)

Deng

Nair

Nukavarapu

et al. 2010

Adv Funct Materials

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“…LTW and HTW biodegradable polymeric microspheres were fabricated with PLAGA copolymer in an 85:15 ratio (Alkermes Medisorb, Wilmington, OH) as described (30,32). The polymer was amorphous and had an inherent viscosity of 0.66-0.80 dl͞g and a glass transition temperature of 50-55°C.…”

Section: Methodsmentioning

confidence: 99%

Bioreactor-based bone tissue engineering: The influence of dynamic flow on osteoblast phenotypic expression and matrix mineralization

Botchwey

Levine

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

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268

195

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An important issue in tissue engineering concerns the possibility of limited tissue ingrowth in tissue-engineered constructs because of insufficient nutrient transport. We report a dynamic flow culture system using high-aspect-ratio vessel rotating bioreactors and 3D scaffolds for culturing rat calvarial osteoblast cells. 3D scaffolds were designed by mixing lighter-than-water (density, <1 g͞ml) and heavier-than-water (density, >1 g͞ml) microspheres of 85:15 poly(lactide-co-glycolide). We quantified the rate of 3D flow through the scaffolds by using a particle-tracking system, and the results suggest that motion trajectories and, therefore, the flow velocity around and through scaffolds in rotating bioreactors can be manipulated by varying the ratio of heavier-than-water to lighter-than-water microspheres. When rat primary calvarial cells were cultured on the scaffolds in bioreactors for 7 days, the 3D dynamic flow environment affected bone cell distribution and enhanced cell phenotypic expression and mineralized matrix synthesis within tissue-engineered constructs compared with static conditions. These studies provide a foundation for exploring the effects of dynamic flow on osteoblast function and provide important insight into the design and optimization of 3D scaffolds suitable in bioreactors for in vitro tissue engineering of bone.

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“…During the heating process, the sintering occurs due to the intertwining of polymer chains between adjacent microspheres, forming bonds. By controlling the size of the microspheres and heat sintering time, the pore size and porosity can be controlled [24][25][26]. Each processing technique has advantages and disadvantages for applications in bone tissue engineering, but all the techniques seek to create scaffolds that have uniform structure and porosity throughout the scaffolds, unlike the natural dual organization in natural bone.…”

Section: Introductionmentioning

confidence: 99%

Fabrication and Characterization of Three-Dimensional Electrospun Scaffolds for Bone Tissue Engineering

Andric

Taylor

Whittington

et al. 2015

Regen. Eng. Transl. Med.

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There are 600,000 bone-grafting procedures performed annually as a result of significant skeletal loss and bone deficiencies. This is an increasing worldwide medical issue as the average life expectancy increases 2-3 % annually. The current standards for bone treatment are autografts and allografts; both of which have drawbacks. Therefore, there is a need for alternative bone graft substitutes such as tissue-engineered grafts. Tissue engineering has emerged as a promising option for bone treatments by using biological or synthetic scaffolds to promote tissue regeneration. The advantages of this treatment include abundant supply and customizable features. The majority of scaffold fabrication techniques used in research focuses on mimicking the porous trabecular bone structure. A major characteristic of optimal scaffold integration and viability is vascularization, which is housed within the osteon canal of the cortical bone. Namely, there is a lack of tissueengineered scaffolds for bone regeneration that mimic both trabecular and cortical bone structures. In this study, we combined two previously fabricated structures, sintered electrospun sheets and individual osteon-like scaffolds, to create scaffolds that mimic dual structural organization of the native bone with cortical and trabecular regions. Scaffolds were successfully mineralized in 10× simulated body fluid (SBF) up to 48 h with enhanced mineral distribution throughout the scaffolds. Mineralization for 24 h significantly increased mechanical properties of the scaffolds. In vitro studies performed over 28 days with mouse-pre-osteoblastic cells, MC3T3-E1s, proved that the mineralized scaffolds promoted cellular attachment, proliferation, and early stages of osteoblastic differentiation in comparison to the non-mineralized scaffolds. The implications of this study lead to the advancement of tissue-engineered mineralized trabecular and cortical bone scaffolds. Lay SummaryThe use of tissue-engineered scaffolds to harness a patients' own bone regenerative properties following traumatic bone loss has emerged as an alternative to current bone-grafting procedures. In this manuscript, the development and characterization process of a synthetic scaffold which mimics both the porous trabecular bone structure and dense cortical bone structure is discussed. Qualitative analysis confirmed the biomimetic porous structure necessary for nutrient transport and cellular infiltration and the cortical canal structure to house vascularization. Various mineralization techniques were investigated to determine the optimal mechanical properties. The scaffold also exhibited the ability to promote osteoblastic cellular attachment and proliferation. The mineral content deposited onto the scaffold led to an increase in osteoblastic behavior of the attached cells; suggesting early stages of osteogenesis. The results of this manuscript indicate the potential of utilizing a tissue-engineering scaffold as a promising treatment for bone tissue regeneration applications.

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Tissue engineered microsphere-based matrices for bone repair:

Cited by 259 publications

References 22 publications

Porous Structures: In situ Porous Structures: A Unique Polymer Erosion Mechanism in Biodegradable Dipeptide‐Based Polyphosphazene and Polyester Blends Producing Matrices for Regenerative Engineering (Adv. Funct. Mater. 17/2010)

Porous Structures: In situ Porous Structures: A Unique Polymer Erosion Mechanism in Biodegradable Dipeptide‐Based Polyphosphazene and Polyester Blends Producing Matrices for Regenerative Engineering (Adv. Funct. Mater. 17/2010)

Bioreactor-based bone tissue engineering: The influence of dynamic flow on osteoblast phenotypic expression and matrix mineralization

Fabrication and Characterization of Three-Dimensional Electrospun Scaffolds for Bone Tissue Engineering

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