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Biomedical subjects

Robert S Langer

Publications and source records attributed to Robert S Langer.

7 recordsLinked to original sources
PubMed2006

A photolithographic method to create cellular micropatterns.

Here we describe a simple and rapid system for creation of patterned cell culture substrates. This technique is based on (1) printing a mask on a standard overhead transparency, (2) coating a thin layer of a photocrosslinkable chitosan on a slide, (3) exposing the slide and mask to ultraviolet (UV) light, and (4) rinsing the uncrosslinked polymer to expose the underlying cell-repellent patterns. Photocross-linkable chitosan does not require photoinitiators, it is non-toxic and forms flexible, biocompatible hydrogel upon short ( approximately min) UV exposure. Patterns of various shapes (lanes, squares, triangles, circles) were created on two surfaces commonly used for cell culture: glass and tissue culture polystyrene. The pattern size could be varied with a mum resolution using a single mask and varying UV exposure time. Cardiac fibroblasts formed stable patterns for up to 18 days in culture. Cardiomyocytes, patterned in lanes 68-99 microm wide, exhibited expression of cardiac Troponin I, well developed contractile apparatus and they contracted synchronously in response to electrical field stimulation. Osteoblasts (SAOS-2) localized in the exposed glass regions (squares, triangles, or circles; 0.063-0.5mm(2)). They proliferated to confluence in 5 days, expressed alkaline phosphatase and produced a mineralized matrix.

Animals↗
PubMed2006

Magnetically responsive polymeric microparticles for oral delivery of protein drugs.

PURPOSE: Protein drugs cannot be delivered efficiently through oral routes. To address this challenge, we evaluated the effect of prolonged gastrointestinal transit on the bioavailability of insulin carried by magnetically responsive microparticles in the presence of an external magnetic field. METHODS: Magnetite nanocrystals and insulin were coencapsulated into poly(lactide-co-glycolide) (PLGA) microparticles and their effects on hypoglycemia were evaluated in mice in the presence of a circumferentially applied external magnetic field. RESULTS: A single administration of 100 U/kg of insulin-magnetite-PLGA microparticles to fasted mice resulted in a reduction of blood glucose levels of up to 43.8% in the presence of an external magnetic field for 20 h (bioavailability = 2.77 +/- 0.46 and 0.87 +/- 0.29% based on glucose and ELISA assay, respectively), significantly higher than similarly dosed mice without a magnetic field (bioavailability = 0.66 +/- 0.56 and 0.30 +/- 0.06%, based on glucose and ELISA assay, respectively). CONCLUSIONS: A substantially improved hypoglycemic effect was observed in mice that were orally administered with insulin-magnetite-PLGA microparticles in the presence of an external magnetic field, suggesting that magnetic force can be used to improve the efficiency of orally delivered protein therapeutics.

Administration, Oral↗
PubMed2005

Cultivation of human embryonic stem cells without the embryoid body step enhances osteogenesis in vitro.

Osteogenic cultures of embryonic stem cells (ESCs) are predominately derived from three-dimensional cell spheroids called embryoid bodies (EBs). An alternative method that has been attempted and merits further attention avoids EBs through the immediate separation of ESC colonies into single cells. However, this method has not been well characterized and the effect of omitting the EB step is unknown. Herein, we report that culturing human embryonic stem cells (hESCs) without the EB stage leads to a sevenfold greater number of osteogenic cells and to spontaneous bone nodule formation after 10-12 days. In contrast, when hESCs were differentiated as EBs for 5 days followed by plating of single cells, bone nodules formed after 4 weeks only in the presence of dexamethasone. Furthermore, regardless of the inclusion of EBs, bone matrix formed, including cement line matrix and mineralized collagen, which displayed apatitic mineral (PO4) with calcium-to-phosphorous ratios similar to those of hydroxyapatite and human bone. Together these results demonstrate that culturing hESCs without an EB step can be used to derive large quantities of functional osteogenic cells for bone tissue engineering.

Alkaline Phosphatase↗
PubMed2005

Biocompatibility analysis of poly(glycerol sebacate) as a nerve guide material.

No satisfactory method currently exists for bridging neural defects. Autografts lead to inadequate functional recovery, and most available artificial neural conduits possess unfavorable swelling and pro-inflammatory characteristics. This study examined the biocompatibility of a novel biodegradable elastomer, poly(glycerol sebacate) (PGS), for neural reconstruction applications, as the material possesses favorable mechanical property and degradation characteristics. The effect of PGS on Schwann cell metabolic activity, attachment, proliferation, and apoptosis were examined in vitro in comparison with poly(lactide-co-glycolide) (PLGA), a biomaterial widely utilized for tissue engineering applications. The in vivo tissue response to PGS was compared with PLGA implanted juxtaposed to the sciatic nerve; the physical changes in the implant material were measured during the degradation process. PGS had no deleterious effect on Schwann cell metabolic activity, attachment, or proliferation, and did not induce apoptosis; the in vitro effects of PGS were similar to or superior to that of PLGA. In vivo, PGS demonstrated a favorable tissue response profile compared with PLGA, with significantly less inflammation and fibrosis and without detectable swelling during degradation. PGS is an excellent candidate material for neural reconstruction applications given its lack of in vitro Schwann cell toxicity and minimal in vivo tissue response.

Animals↗
PubMed2004

Single-chain antibody fragment-based adsorbent for the extracorporeal removal of beta2-microglobulin.

BACKGROUND: Dialysis-related amyloidosis (DRA) is a frequent complication of end-stage renal disease (ESRD) that has been associated with the accumulation of beta2-microglobulin (beta2-m). Removal of beta2-m results in the loss of important proteins due to the nonspecific nature of current therapies. Although whole antibodies can potentially be used to confer specificity to beta2-m removal from blood, single-chain variable region (scFv) antibody fragments could potentially offer several advantages as immunoadsorption ligands due to their size, genetic definition, ability to be expressed by microbes, and amenability for in vitro evolution. METHODS: An antihuman beta2-m scFv was constructed from the BBM.1 hybridoma and expressed by a yeast display vector. The binding affinity of the wild-type scFv fragment was quantified by flow cytometry analysis. Soluble scFv was expressed by a yeast secretion vector, purified, and immobilized onto agarose beads. The binding capacity of the immunoadsorbent was measured by equilibrating samples with saturating quantities of fluorescent beta2-m in serum. RESULTS: The displayed scFv possessed a nanomolar affinity (KD= 0.008 +/- 0.004 mg-beta2-m/L). The immunoadsorbent exhibited an adsorption site density of 0.41 +/- 0.01 mg beta2-m/mL settled gel. Under saturating conditions, the mass ratio of adsorbed beta2-m to immobilized antibody is 70% greater than any previous literature report for whole antibodies. Preliminary specificity experiments suggest that the scFv-based immunoadsorbent is specific toward human beta2-m. CONCLUSION: Recombinant DNA technology was successfully used to engineer an scFv-based immunoadsorbent. Use of immobilized scFvs during hemodialysis may minimize loss of valuable proteins and facilitate the removal of macromolecules that are significantly larger than the molecular weight cut-off of the membrane.

Amino Acid Sequence↗
PubMed2002

Polyanhydrides: an overview.

Polyanhydrides have been considered to be useful biomaterials as carriers of drugs to various organs of the human body such as brain, bone, blood vessels, and eyes. They can be prepared easily from available, low cost resources and can be manipulated to meet desirable characteristics. Polyanhydrides are biocompatible and degrade in vivo into non-toxic diacid counterparts that are eliminated from the body as metabolites. Owing to their usefulness, this review focuses on the development, synthesis methods, structures and characterization of polyanhydrides, which will provide an overview for the researchers in the field. Their in vitro and in vivo degradability, toxicity, biocompatibility and applications are discussed in the subsequent chapters of this special issue on polyanhydrides and poly(ortho esters).

Anhydrides↗