Biomedical subjects

Robert Langer

Publications and source records attributed to Robert Langer.

188 records · Page 11Linked to original sources

PubMedDate not supplied

Degradable poly(amino alcohol esters) as potential DNA vectors with low cytotoxicity.

The synthesis of a new degradable polymer system, poly(amino alcohol esters) and the resulting polymers' potential for use in gene transfection vectors are reported. The polymerization proceeded in a one step reaction from commercially available bis(secondary amines) monomers (N,N'-dimethyl-1,3-propanediamine and N,N'-dimethyl-1,6-hexanediamine, respectively) through nucleophilic addition to the diglycidyl ester of dicarboxylic acid (diglycidyl adipate). Poly(amino alcohol ester) 1 and 2 were synthesized with a yield of 89% and 91% with Mn = 24,800 and Mn = 36,400, respectively. Poly(amino alcohol ester) 1 degraded hydrolytically in phosphate buffer at pH 7.4 with a half-life of approximately 5 days. Both polymers readily self-assembled with plasmid DNA into nanometer-sized DNA/polymer complexes less than 180 nm diameter and are significantly less cytotoxic than the commonly used DNA delivery polymer, poly(ethylene imine) (PEI).

3T3 Cells↗

PubMedDate not supplied

Controlled degradation and mechanical behavior of photopolymerized hyaluronic acid networks.

Hyaluronic acid is a natural polysaccharide found abundantly throughout the body with many desirable properties for application as a biomaterial, including scaffolding for tissue engineering. In this work, hyaluronic acid with molecular weights ranging from 50 to 1100 kDa was modified with methacrylic anhydride and photopolymerized into networks with a wide range of physical properties. With macromer concentrations from 2 to 20 wt %, networks exhibited volumetric swelling ratios ranging from approximately 42 to 8, compressive moduli ranging from approximately 2 to over 100 kPa, and degradation times ranging from less than 1 day up to almost 38 days in the presence of 100 U/mL of hyaluronidase. When 3T3-fibroblasts were photoencapsulated in the hydrogels, cells remained viable with low macromer concentrations but decreased sequentially as the macromer concentration increased. Finally, auricular swine chondrocytes produced neocartilage when photoencapsulated in the hyaluronic acid networks. This work presents a next step toward the development of advanced in vivo curable biomaterials.

3T3 Cells↗

PubMedDate not supplied

Poly(ethylene oxide)-modified poly(beta-amino ester) nanoparticles as a pH-sensitive system for tumor-targeted delivery of hydrophobic drugs. 1. In vitro evaluations.

A representative poly(beta-amino ester) (PbAE) with biodegradable and pH-sensitive properties was used to formulate a nanoparticle-based dosage form for tumor-targeted paclitaxel delivery. The polymer undergoes rapid dissolution when the pH of the medium is less than 6.5 and hence is expected to release its contents at once within the acidic tumor microenvironment and endo/lysosome compartments of cells. PbAE nanoparticles were prepared by solvent displacement method and characterized for particle size, charge, and surface morphology. Pluronic F-108, a triblock copolymer of poly(ethylene oxide) (PEO) and poly(propylene oxide) (PPO), was blended with PbAE to induce surface modification of the nanoparticles. In vitro cellular uptake of tritiated [(3)H]-paclitaxel in solution form and as a nanoparticulate formulation was studied in MDA-MB-231 human breast adenocarcinoma cells grown in 12-well plates. We also examined the intracellular degradation pattern of the formulations within the cells by estimating the drug release profile. Cytotoxicity assay was performed on the formulations at different doses and time intervals. Nanoparticles prepared from poly(epsilon-caprolactone) (PCL) that do not display pH-sensitive release behavior were used as control. Spherical nanoparticles having positive zeta potential ( approximately 40 mV) were obtained in the size range of 150-200 nm with PbAE. The PEO chains of the Pluronic were well-anchored within the nanomatrix as determined by electron spectroscopy for chemical analysis (ESCA). The intracellular accumulation of paclitaxel within tumor cells was significantly higher when administered in the nanoparticle formulations as compared to aqueous solution. Qualitative fluorescent microscopy confirmed the rapid release of the payload into the cytosol in the case of PbAE nanoparticles, while the integrity of the PCL nanoparticles remained intact. The cytotoxicity assay results showed significantly higher tumoricidal activity of paclitaxel when administered in the nanoparticle formulations. The cell-kill effect was maximal for paclitaxel-loaded PbAE nanoparticles when normalized with respect to intracellular drug concentrations. Thus, PEO-modified PbAE nanoparticles show tremendous potential as novel carriers of cytotoxic agents for achieving improved drug disposition and enhanced efficacy.

Cell Line, Tumor↗

PubMedDate not supplied

Hydraulic elevation of the periosteum: a novel technique for periosteal harvest.

Periosteum has been promoted as a potential substrate for tissue engineering. Its principal virtues are that it has a source of pluripotential mesenchymal cells and chondrogenic growth factors located in the cambium layer, and it can serve as a template for directional evolution of neo-tissue. The clinical use and in vitro study of periosteum-derived neo-tissue has been limited by the level of surgical skill required for harvest. Precise surgical technique, task-specific experience, adequate volume of procedures, and general surgical expertise are required for optimal harvest using the traditional periosteal elevator method. This report describes an easily mastered technique that preserves viability while providing the harvest of relatively large amounts of periosteum. Skeletally mature New Zealand white rabbits (11 males/20 tibias; 4 females/8 tibias; approximate weight 3.5 kg) and one Yucatan miniature pig were used for harvest of periosteum from the tibia using the traditional periosteal elevator and the developed hydraulic elevation approach. Histologic examination of the periosteal explants obtained by the developed method showed preservation of the cambium layer containing the progenitor cells necessary for the generation of neo-cartilage. This technique provides a simple method of harvesting large segments (>5 cm x 1 cm) of periosteum in a single procedure and may facilitate better exploitation of periosteum in tissue engineering.

Animals↗

PubMedDate not supplied

Tissue engineering of fish skin: behavior of fish cells on poly(ethylene glycol terephthalate)/poly(butylene terephthalate) copolymers in relation to the composition of the polymer substrate as an initial step in constructing a robotic/living tissue hybrid.

This study presents the development of a biosynthetic fish skin to be used on aquatic robots that can emulate fish. Smoothness of the external surface is desired in improving high propulsive efficiency and maneuvering agility of autonomous underwater vehicles such as the RoboTuna (Triantafyllou, M., and Triantafyllou, G. Sci. Am. 272, 64, 1995). An initial step was to determine the seeding density and select a polymer for the scaffolds. The attachment and proliferation of chinook salmon embryo (CHSE-214) and brown bullhead (BB) cells were studied on different compositions of a poly(ethylene glycol terephthalate) (PEGT) and poly(butylene terephthalate) (PBT) copolymer (Polyactive). Polymer films were used, cast of three different compositions of PEGT/PBT (weight ratios of 55/45, 60/40, and 70/30) and two different molecular masses of PEGT (300 and 1000 Da). When a 55 wt% and a 300-Da molecular mass form of PEGT was used, maximum attachment and proliferation of CHSE-214 and BB cells were achieved. Histological studies and immunostaining indicate the presence of collagen and cytokeratins in the extracellular matrix formed after 14 days of culture. Porous scaffolds of PEGT/PBT copolymers were also used for three-dimensional tissue engineering of fish skin, using BB cells. Overall, our results indicate that fish cells can attach, proliferate, and express fish skin components on dense and porous Polyactive scaffolds.

Animals↗

PubMedDate not supplied

Endothelialized microvasculature based on a biodegradable elastomer.

Vital organs maintain dense microvasculature to sustain the proper function of their cells. For tissue- engineered organs to function properly, artificial capillary networks must be developed. We have microfabricated capillary networks with a biodegradable and biocompatible elastomer, poly(glycerol sebacate) (PGS). We etched capillary patterns onto silicon wafers by standard micro-electromechanical systems (MEMS) techniques. The resultant silicon wafers served as micromolds for the devices. We bond the patterned PGS film with a flat film to create capillary networks that were perfused with a syringe pump at a physiological flow rate. The devices were endothelialized under flow conditions, and part of the lumens reached confluence within 14 days of culture. This approach may lead to tissue-engineered microvasculature that is critical in vital organs engineering.

Biocompatible Materials↗

PubMedDate not supplied

Neurotrophin-induced differentiation of human embryonic stem cells on three-dimensional polymeric scaffolds.

Human embryonic stem (hES) cells have the potential to form various cell types, including neural cells for the treatment of diseases such as Parkinson's, spinal cord injury, and glaucoma. Here, we have investigated the neuronal differentiation of hES cells on three-dimensional scaffolds fabricated from degradable poly(alpha-hydroxy esters) including poly(lactic-co-glycolic acid) and poly(L-lactic acid). When cultured in vitro, neural rosette-like structures developed throughout the scaffolds with differentiation dependent on factors in the medium (e.g., retinoic acid [RA], nerve growth factor [NGF], and neurotrophin 3 [NT-3]) and the differentiation stage of the cells. Specifically, enhanced numbers of neural structures and staining of nestin (a marker of neural precursors) and beta(III)-tubulin (indicative of neural differentiation) were observed with hES cell-seeded polymer scaffolds when cultured with both NGF and NT-3 when compared with control medium. In addition, vascular structures were found throughout the engineered tissues when cultured with the neurotrophins, but not in the presence of RA.

Cell Culture Techniques↗

PubMedDate not supplied

Biodegradable polymer composite grafts promote the survival and differentiation of retinal progenitor cells.

Retinal progenitor cells (RPCs) are multipotent central nervous system precursors that give rise to all of the cell types of the retina during development. Several groups have reported that mammalian RPCs can be isolated and expanded in culture and can differentiate into retinal neurons upon grafting to the mature, diseased eye. However, cell delivery and survival remain formidable obstacles to application of RPCs in a clinical setting. Because biodegradable polymer/progenitor constructs have been shown to be capable of tissue generation in other compartments, we evaluated the survival, migration, and differentiation of RPCs delivered on PLLA/PLGA polymer substrates to the mouse subretinal space and compared these results to conventional injections of RPCs. Polymer composite grafts resulted in a near 10-fold increase in the number of surviving cells after 4 weeks, with a 16-fold increase in cell delivery. Grafted RPCs migrated into the host retina and expressed the mature markers neurofilament-200, glial fibrillary acidic protein, protein kinase C-alpha, recoverin, and rhodopsin. We conclude that biodegradable polymer/progenitor cell composite grafts provide an effective means of increasing progenitor cell survival and overall yield when transplanting to sites within the central nervous system such as the retina.

Absorbable Implants↗