Novel approach to fabricate porous sponges of poly(d,l-lactic-co-glycolic acid) without the use of organic solvents

Mooney, David J.; Baldwin, D.F.; Suh, Nam P.; Vacanti, Joseph P.; Langer, Robert

doi:10.1016/0142-9612(96)87284-x

Cited by 1,001 publications

(615 citation statements)

References 10 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%

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%

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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“…Although this technique has advanced the overall science of controlled drug delivery in tissue engineering, unintended release of residual solvent trapped in the polymer after processing is harmful to adherent cells, local growth factors, and neighboring tissue. 221,[313][314][315][316][317][318] Residual organic solvents in a polymer scaffold limit or prevent the encapsulation of active growth factors and hence functionality of the scaffold. Therefore, novel solvent-free techniques are being aggressively pursed.…”

Section: Antibiotics and Chemotherapeuticsmentioning

confidence: 99%

“…Therefore, novel solvent-free techniques are being aggressively pursed. Some examples of solvent-free scaffold fabrication techniques include: sintering/compression followed by ultrasonic welding, 264,285 hot melt encapsulation, 313,315,319 high pressure CO 2,314 and mechanical mixing. In hot melt encapsulation, the processing temperature must be below the denaturation or deactivation temperature of the bioactive molecule or drug encapsulated.…”

Section: Antibiotics and Chemotherapeuticsmentioning

confidence: 99%

Bone tissue engineering: A review in bone biomimetics and drug delivery strategies

Porter

Ruckh

Popat

2009

Biotechnology Progress

672

499

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Critical‐sized defects in bone, whether induced by primary tumor resection, trauma, or selective surgery have in many cases presented insurmountable challenges to the current gold standard treatment for bone repair. The primary purpose of a tissue‐engineered scaffold is to use engineering principles to incite and promote the natural healing process of bone which does not occur in critical‐sized defects. A synthetic bone scaffold must be biocompatible, biodegradable to allow native tissue integration, and mimic the multidimensional hierarchical structure of native bone. In addition to being physically and chemically biomimetic, an ideal scaffold is capable of eluting bioactive molecules (e.g., BMPs, TGF‐βs, etc., to accelerate extracellular matrix production and tissue integration) or drugs (e.g., antibiotics, cisplatin, etc., to prevent undesired biological response such as sepsis or cancer recurrence) in a temporally and spatially controlled manner. Various biomaterials including ceramics, metals, polymers, and composites have been investigated for their potential as bone scaffold materials. However, due to their tunable physiochemical properties, biocompatibility, and controllable biodegradability, polymers have emerged as the principal material in bone tissue engineering. This article briefly reviews the physiological and anatomical characteristics of native bone, describes key technologies in mimicking the physical and chemical environment of bone using synthetic materials, and provides an overview of local drug delivery as it pertains to bone tissue engineering is included. © 2009 American Institute of Chemical Engineers Biotechnol. Prog., 2009

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“…An overall rating was obtained using weighting factors (53 for the capsular thickness, 33 for the cellular response observed in the capsule, 53 for the neutrophils, 23 for the FBGCs, 13 for the lymphocytes, 13 for macrophages, and 13 for the fibroblasts). Reactions were classified into 6 categories, which were as follows: no reaction (0), minimal (1-10), slight (11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25), moderate (26)(27)(28)(29)(30)(31)(32)(33)(34)(35)(36)(37)(38)(39)(40), marked (41-60), and excessive (>60).…”

Section: Histological Evaluationmentioning

confidence: 99%

“…Use of supercritical CO 2 allows the incorporation of biological agents and ceramic particles, and the manufacture of open pore foams with low intrinsic viscosity amorphous PLGA (polylactic-co-glycolic acid). [38][39][40] In this study we focused on semicrystalline PLA, which allowed us obtaining open pore scaffolds with controlled porosity and morphology and improved mechanical properties, thus creating for bone cells an environment similar to natural bone.…”

Section: Introductionmentioning

confidence: 99%

Repair of critical size defects in the rat cranium using ceramic‐reinforced PLA scaffolds obtained by supercritical gas foaming

Montjovent

Mathieu

Schmoekel

et al. 2007

J Biomedical Materials Res

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Bioresorbable scaffolds made of poly(L-lactic acid) (PLA) obtained by supercritical gas foaming were recently described as suitable for tissue engineering, portraying biocompatibility with primary osteoblasts in vitro and interesting mechanical properties when reinforced with ceramics. The behavior of such constructs remained to be evaluated in vivo and therefore the present study was undertaken to compare different PLA/ceramic composite scaffolds obtained by supercritical gas foaming in a critical size defect craniotomy model in Sprague-Dawley rats. The host-tissue reaction to the implants was evaluated semiquantitatively and similar tendencies were noted for all graft substitutes: initially highly reactive but decreasing with time implanted. Complete bonebridging was observed 18 weeks after implantation with PLA/ 5 wt % b-TCP (PLA/TCP) and PLA/5 wt % HA (PLA/HA) scaffolds as assessed by histology and radiography. We show here for the first time that this solvent-free technique provides a promising approach in tissue engineering demonstrating both the biocompatibility and osteoconductivity of the processed structures in vivo.

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Novel approach to fabricate porous sponges of poly(d,l-lactic-co-glycolic acid) without the use of organic solvents

Cited by 1,001 publications

References 10 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)

Bone tissue engineering: A review in bone biomimetics and drug delivery strategies

Repair of critical size defects in the rat cranium using ceramic‐reinforced PLA scaffolds obtained by supercritical gas foaming

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