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C T Laurencin

Publications and source records attributed to C T Laurencin.

At least 19 recordsLinked to original sources
PubMed2006

Formation of hydroxyapatite-polyphosphazene polymer composites at physiologic temperature.

Aspects of the formation of bone analog composites at 37 degrees C are described. The composites are composed of hydroxyapatite (HAp) and the calcium salt of a biocompatible polymer and are capable of forming under in vivo conditions. Composite formation involves the formation of monolithic HAp from particulate calcium phosphate precursors while Ca ions liberated to the aqueous medium in which this reaction is occurring form crosslinks with the acidic polymer. The reactants are poly[bis(carboxylatophenoxy)phosphazene] (acid-PCPP), tetracalcium phosphate [Ca4(PO4)2O, TetCP], and anhydrous dicalcium phosphate (CaHPO4, DCPA). The effects of the proportion of polymer (5, 10, or 15 wt %) on the kinetics of HAp formation were studied. Compositional evolution of the solid calcium phosphates present was followed by X-ray diffraction and infrared spectroscopy analyses. HAp formation through a dissolution-precipitation process provided a mildly alkaline medium suitable for deprotonation of the acid-PCPP and for the formation of the calcium crosslinks, as monitored by infrared spectroscopy. Concurrence of crosslinking of the polymer and HAp formation was established, indicating true composite formation can be realized at physiologic temperature.

Biocompatible Materials↗
PubMed2005

Composite formation from hydroxyapatite with sodium and potassium salts of polyphosphazene.

The low temperature synthesis of composites potentially suitable as bone substitutes which form in vivo, was investigated. The composites were comprised of stoichiometric hydroxyapatite (SHAp) and water-soluble poly phosphazenes. These constituents were selected because of their biocompatibility, and were mixed as powders with a phosphate buffer solution (PBS) to form the composites. The effects of poly[bis(sodium carboxylatophenoxy)phosphazene] (Na-PCPP) or poly[bis(potassium carboxylatophenoxy) phosphazene] (K-PCPP) on stoichiometric hydroxyapatite (SHAp) formation from tetracalcium phosphate and anhydrous dicalcium phosphate were assessed. The kinetics and reaction chemistries of composite formation were followed by isothermal calorimetry, X-ray diffraction, infrared spectroscopy and scanning electron microscopy. In the presence of 1% by weight of polyphosphazenes, composites comprised of SHAp and calcium cross-linked polymer salts were formed. Thus a mechanism for binding between polymer chains was established. Elevated proportions (5 and 10% by weight) of polyphosphazene, however, resulted in the inhibition of SHAp formation. This is attributed to the formation of viscous polymer solution coatings on the calcium phosphate precursors, retarding their reaction, and consequently inhibiting SHAp formation.

Biocompatible Materials↗
PubMed2005

Low temperature formation of hydroxyapatite-poly(alkyl oxybenzoate)phosphazene composites for biomedical applications.

The formation of biodegradable composites which may be suitable as bone analogs is described. Polyphosphazene-hydroxyapatite (HAp) composites were produced via an acid-base reaction of tetracalcium phosphate and anhydrous dicalcium phosphate in the presence of polyphosphazenes bearing alkyl ester containing side-groups. The polyphosphazenes used were poly(ethyl oxybenzoate)phosphazene (PN-EOB) and poly(propyl oxybenzoate) phosphazene (PN-POB). The effects of temperature and the proportions of polymers, PN-EOB and PN-POB on the kinetics, reaction chemistry and phase evolution during the formation of stoichiometric HAp were studied. Kinetics, phase evolution and microstructural development were evaluated using isothermal calorimetry, X-ray diffraction and scanning electron microscopy, respectively. Analysis of solution chemistry revealed that the increases in the pH during the formation of SHAp, resulted in partial hydrolysis of the polymer surfaces, which led in turn to the formation of a calcium cross-linked polymer surface. The calcium cross-linked polymer surface appeared to facilitate the nucleation and growth of apatite deposits on the polymer. The current study illustrates the in situ formation of HAp in the presence of polyphosphazenes, where HAp is chemically bonded to the polymer.

Absorbable Implants↗
PubMed2005

Orthopaedic applications of gene therapy.

Current treatment modalities for musculoskeletal injuries due to disease or trauma often implement the use of tissue grafts, cell transplantations, and artificial scaffolding. These approaches may be augmented with the use of specific biological factors, which accelerate healthy tissue regeneration. Unfortunately, the short half-life and inherent instability of proteins requires the delivery of high doses or multiple doses of these molecules, neither of which is ideal for the patient or clinician. Gene therapy, as an alternative approach, has the potential to circumvent the existing limitations associated with protein delivery by producing a sustained release of the biologic agent at therapeutic levels. This is achieved by the direct transfer of the gene encoding the therapeutic agent to the cells of the afflicted tissue or by implanting cells that have been previously genetically modified in vitro. Using these methods, several laboratories have demonstrated the ability to deliver genes in vitro and in vivo resulting in accelerated and enhanced musculoskeletal tissue regeneration or inhibited disease progression. Many of these investigations, which involved bone, ligament, tendon, and cartilage, are covered in this review. Specifically, musculoskeletal tissue anatomy, factors relevant to musculoskeletal tissue regeneration, target cells, and in vivo and ex vivo gene therapy approaches for musculoskeletal regeneration are discussed. The experience and knowledge gained from these studies have affirmed gene therapy is a promising therapeutic strategy to combat musculoskeletal tissue repair and regeneration following disease or injury.

Genetic Therapy↗
PubMed2004

Tissue-engineered bone formation in vivo using a novel sintered polymeric microsphere matrix.

We have evaluated in vivo a novel, polymer-based, matrix for tissue engineering of bone. A segmental defect of 15 mm was created in the ulna of New Zealand white rabbits to determine the regenerative properties of a porous polylactide-co-glycolide matrix alone and in combination with autogenous marrow and/or the osteoinductive protein, BMP-7. In this study four implant groups were used: 1) matrix alone; 2) matrix with autogenous marrow; 3) matrix with 20 microg of BMP-7; and 4) matrix with 20 microg of BMP-7 and autogenous marrow. The results showed that the degree of bone formation was dependent on the properties of the graft material. The osteoconductive sintered matrix structure showed significant formation of bone at the implant-bone interface. The addition of autogenous marrow increased the penetration of new bone further into the central area of the matrix and also increased the degree of revascularisation. The osteoinductive growth factor BMP-7 induced penetration of new bone throughout the entire structure of the implant. The most effective treatment was with the combination of marrow cells and osteoinductive BMP-7.

Animals↗
PubMed2003

Biodegradable polyphosphazenes for drug delivery applications.

Biodegradable polymers such as poly(alpha-hydroxy acids), poly(anhydrides), poly(ortho esters), poly(amino acids) and polyphosphazenes have raised considerable interest as short-term medical implants due to their transient nature. Among these, polyphosphazenes are a relatively new class of polymers, quite distinct from all the biodegradable polymers synthesized so far, due to their synthetic flexibility and versatile adaptability for applications. These are high molecular weight, essentially linear polymers with an inorganic backbone of alternating phosphorous and nitrogen atoms bearing two side groups attached to each phosphorous atom. Controlled tuning of physico-chemical properties, including biodegradability, can be achieved in this class of polymers via macromolecular substitutions. Biodegradable polyphosphazenes, due to their hydrolytic instability, nontoxic degradation products, ease of fabrication and matrix permeability, are an excellent platform for controlled drug delivery applications. This review discusses the mode of degradation and drug delivery applications of biodegradable polyphosphazenes.

Animals↗
PubMed2003

Structural and human cellular assessment of a novel microsphere-based tissue engineered scaffold for bone repair.

The limitations of current grafting materials have driven the search for synthetic alternatives for the regeneration of trabecular bone. A variety of biodegradable polymer foams composed of 85/15 poly(lactide-co-glycolide) (PLAGA) have been evaluated for such uses. However, structural limitations may restrict the clinical use of these scaffolds. We have developed a novel sintered microsphere scaffold with a biomimetic pore system equivalent to the structure of trabecular bone. By modifying processing parameters, several different sintered microsphere structures were fabricated. Optimization of the structure dealt with modifications to sphere diameter and heating time. Compressive testing illustrated a trend between microsphere diameter and modulus, where increased microsphere diameter resulted in decreased modulus. In addition, evaluation of the pore system showed a positive correlation between sphere diameter and pore diameter. Mercury porosimetry showed increased median pore size with an increased microsphere diameter. Heating time modifications showed that compressive modulus was dependent on the period of heating with longer heating times resulting in higher moduli. It was also shown that heating time did not affect the pore structure. Analysis of the structural data indicated that the microsphere matrix sintered for 4h at a temperature of 160 degrees C with a microsphere diameter of 600-710 microm resulted in an optimal, biomimetic structure with range in pore diameter of 83-300 microm, a median pore size of 210 microm, 35% porosity, and a compressive modulus of 232 MPa. An in vitro evaluation of human osteoblasts seeded onto the sintered matrix indicated that the structure was capable of supporting the attachment and proliferation of cells throughout its pore system. Immunofluorescent staining of actin showed that the cells were proliferating three-dimensionally through the pore system. The stain for osteocalcin was used and showed that cells maintained phenotypic expression for this bone specific protein. Through this work, it was shown that an osteoconductive PLAGA scaffold with a pore system used as a reverse template to the structure of trabecular bone could be fabricated through the sintered microsphere method.

Actins↗
PubMed2003

Extracellular matrix production by human osteoblasts cultured on biodegradable polymers applicable for tissue engineering.

The nature of the extracellular matrix (ECM) is crucial in regulating cell functions via cell-matrix interactions, cytoskeletal organization, and integrin-mediated signaling. In bone, the ECM is composed of proteins such as collagen (CO), fibronectin (FN), laminin (LM), vitronectin (VN), osteopontin (OP) and osteonectin (ON). For bone tissue engineering, the ECM should also be considered in terms of its function in mediating cell adhesion to biomaterials. This study examined ECM production, cytoskeletal organization, and adhesion of primary human osteoblastic cells on biodegradable matrices applicable for tissue engineering, namely polylactic-co-glycolic acid 50:50 (PLAGA) and polylactic acid (PLA). We hypothesized that the osteocompatible, biodegradable polymer surfaces promote the production of bone-specific ECM proteins in a manner dependent on polymer composition. We first examined whether the PLAGA and PLA matrices could support human osteoblastic cell growth by measuring cell adhesion at 3, 6 and 12h post-plating. Adhesion on PLAGA was consistently higher than on PLA throughout the duration of the experiment, and comparable to tissue culture polystyrene (TCPS). ECM components, including CO, FN, LM, ON, OP and VN, produced on the surface of the polymers were quantified by ELISA and localized by immunofluorescence staining. All of these proteins were present at significantly higher levels on PLAGA compared to PLA or TCPS surfaces. On PLAGA, OP and ON were the most abundant ECM components, followed by CO, FN, VN and LN. Immunofluorescence revealed an extracellular distribution for CO and FN, whereas OP and ON were found both intracellularly as well as extracellularly on the polymer. In addition, the actin cytoskeletal network was more extensive in osteoblasts cultured on PLAGA than on PLA or TCPS. In summary, we found that osteoblasts plated on PLAGA adhered better to the substrate, produced higher levels of ECM molecules, and showed greater cytoskeletal organization than on PLA and TCPS. We propose that this difference in ECM composition is functionally related to the enhanced cell adhesion observed on PLAGA. There is initial evidence that specific composition of the PLAGA polymer favors the ECM. Future studies will seek to optimize ECM production on these matrices for bone tissue engineering applications.

Biodegradation, Environmental↗
PubMed2002

Toxicity, biodegradation and elimination of polyanhydrides.

Although originally developed for the textile industry, polyanhydrides have found extensive use in biomedical applications due to their biodegradability and excellent biocompatibility. Polyanhydrides are most commonly synthesized from diacid monomers by polycondensation. Efficient control over various physicochemical properties, such as biodegradability and biocompatibility, can be achieved for this class of polymers, due to the availability of a wide variety of diacid monomers as well as by copolymerization of these monomers. Biodegradation of these polymers takes place by the hydrolysis of the anhydride bonds and the polymer undergoes predominantly surface erosion, a desired property to attain near zero-order drug release profile. This review examines the mode of degradation and elimination of these polyanhydrides in vivo as well as the biocompatibility and toxicological aspects of various polyanhydrides.

Anhydrides↗
PubMed2001

A novel amorphous calcium phosphate polymer ceramic for bone repair: I. Synthesis and characterization.

Traditional materials for bone repair or replacements such as autografts and allografts have a limited supply and other complications. Thus, alternative materials need to be explored. Three-dimensional, porous composites prepared from bioresorbable polymers and hydroxyapatite or other calcium phosphate ceramics are promising materials for the repair or replacement of diseased or damaged bone. However, in many cases the ceramic component of these composites is crystalline in nature, while bone apatite is made of a poorly crystalline, carbonated phosphate system. In this study, we synthesized a noncrystalline, carbonated calcium phosphate ceramic by carrying out the reaction within bioresorbable PLAGA microspheres using a modified emulsion/solvent evaporation technique, making each individual microsphere a composite. Sintering the composite microspheres together yielded a bioresorbable, porous, 3-dimensional scaffold that may be ideal for tissue ingrowth, making this composite scaffold potentially suitable for bone repair applications.

Bone Substitutes↗
PubMed2001

Regional drug delivery with radiation for the treatment of Ewing's sarcoma. In vitro development of a taxol release system.

Recently, several studies have suggested the radiosensitizing effect of taxol, a microtubular inhibitor. Our overall hypothesis is that a combination of radiation and taxol may demonstrate therapeutic efficacy over doses of either individually. Studies examining taxol use have mostly focused on systemic administration, which can lead to undesired effects. To circumvent these side effects, we propose a locally administered polymeric microsphere delivery system combined with radiation therapy for the treatment of Ewing's sarcoma. The present study focuses on the in vitro ability of taxol when present as a microencapsulated drug delivery system, and delivered locally at the site of the sarcoma/tumor, to block cells in the G2/M phase of the cell cycle and potentially enhance the radiation sensitivity of cells. Using the bioresorbable poly(anhydride-co-imide), poly[pyromellityl-imidoalanine-1,6-bis(carboxy-phenoxy)hexane] (PMA-CPH), and the radiosensitizing agent taxol, a microsphere based delivery system was fabricated. A solvent evaporation technique was used to encapsulate taxol at doses of 1%, 5%, and 10% in PMA-CPH microspheres. Release kinetics studies demonstrated that the total amount of taxol released and the release rate were directly dependent on loading percentage. Taxol's bioactivity and radiosensitizing ability were measured using flow cytometry. Co-culture of Ewing's sarcoma cells with and without taxol-loaded microspheres demonstrated that released taxol retained its bioactivity and effectively blocked cells in the radiosensitive G2/M phase of mitosis. The taxol-radiation delivery system studied achieved an 83% decrease in tumor cell count compared to control. Taxol effectively sensitized Ewing's sarcoma cells to radiation with radiosensitivity shown to be independent of radiation dose at levels of dosages studied. This work has demonstrated that taxol can be effectively released from a biodegradable PMA-CPH microsphere delivery system while maintaining potent combined cytotoxic and radiosensitizing abilities.

Antineoplastic Agents, Phytogenic↗
PubMed2001

Bone tissue engineering in a rotating bioreactor using a microcarrier matrix system.

A novel approach was utilized to grow in vitro mineralized bone tissue using lighter-than-water, polymeric scaffolds in a high aspect ratio rotating bioreactor. We have adapted polymer microencapsulation methods for the formation of hollow, lighter-than-water microcarriers of degradable poly(lactic-co-glycolic acid). Scaffolds were fabricated by sintering together lighter-than-water microcarriers from 500 to 860 microm in diameter to create a fully interconnected, three-dimensional network with an average pore size of 187 microm and aggregate density of 0.65 g/mL. Motion in the rotating bioreactor was characterized by numerical simulation and by direct measurement using an in situ particle tracking system. Scaffold constructs established a near circular trajectory in the fluid medium with a terminal velocity of 98 mm/s while avoiding collision with the bioreactor wall. Preliminary cell culture studies on these scaffolds show that osteoblast-like cells readily attached to microcarrier scaffolds using controlled seeding conditions with an average cell density of 6.5 x 10(4) cells/cm(2). The maximum shear stress imparted to attached cells was estimated to be 3.9 dynes/cm(2). In addition, cells cultured in vitro on these lighter-than-water scaffolds retained their osteoblastic phenotype and showed significant increases in alkaline phosphatase expression and alizarin red staining by day 7 as compared with statically cultured controls.

Alkaline Phosphatase↗
PubMed2001

Poly(lactide-co-glycolide)/hydroxyapatite delivery of BMP-2-producing cells: a regional gene therapy approach to bone regeneration.

Currently, functional treatment of fracture non-unions and bone loss remains a significant challenge in the field of orthopaedic surgery. Tissue engineering of bone has emerged as a new treatment alternative in bone repair and regeneration. Our approach is to combine a polymeric matrix with a cellular vehicle for delivery of bone morphogenetic protein-2 (BMP-2), constructed through retroviral gene transfer. The objective of this study is to develop an osteoinductive, tissue-engineered bone replacement system by culturing BMP-2-producing cells on an osteoconductive, biodegradable, polymeric-ceramic matrix. The hypothesis is that retroviral gene transfer can be used effectively in combination with a biodegradable matrix to promote bone formation. First, we examined the in vitro attachment and growth of transfected BMP-producing cells on a PLAGA-HA scaffold. Second, the bioactivity of the produced BMP in vitro was evaluated using a mouse model. It was found that the polymer-ceramic scaffold supported BMP-2 production, allowing the attachment and growth of retroviral transfected, BMP-2-producing cells. In vivo, the scaffold successfully functioned as a delivery vehicle for bioactive BMP-2, as it induced heterotopic bone formation in a SCID mouse model.

Animals↗
PubMed1999

Proliferation, morphology, and protein expression by osteoblasts cultured on poly(anhydride-co-imides).

In vitro cell biocompatibility models are crucial in the study of any newly synthesized material. Our focus has been on the development of a new class of biocompatible, degradable, high-strength polymeric materials, the poly(anhydride-co-imides), for use in bone regeneration. This study examined osteoblast cell adherence, proliferation, viability, and phenotypic preservation on the surface of the poly(anhydride-co-imide) poly[pyromellitylimidoalanine (PMA-ala):1,6-bis(carboxyphenoxy) hexane (CPH)] over a period of time. Cell proliferation on PMA-ala:CPH degradable matrices over 21 days was examined. Throughout the 21-day period of study, osteoblast proliferation was similar on PMA-ala:CPH and on tissue culture polystyrene controls. Osteoblasts maintained their characteristic morphology as demonstrated by both scanning electron microscopy and immunofluorescence studies. Alkaline phosphatase activity for cells grown on PMA-ala:CPH was confirmed. Retention of the osteoblastic phenotype was demonstrated using immunofluorescence techniques and staining with antibodies against osteocalcin (an extracellular matrix protein of bone) and osteopontin (a marker of cell adhesion). Radioimmunoassay results provided evidence that levels of osteocalcin production by osteoblasts were similar when cells were cultured on PMA-ala:CPH and on tissue culture polystyrene controls. The present study provided evidence of normal osteoblast function on PMA-ala:CPH surfaces. PMA-ala:CPH may therefore be useful as a synthetic material for orthopedic applications.

Animals↗
PubMed1999

The arthroscopic drainage, irrigation, and débridement of late, acute total hip arthroplasty infections: average 6-year follow-up.

We present our experience with arthroscopy for the treatment of late, acute periprosthetic hip infections in 8 consecutive patients, treated from 1989 to 1994. After a hip aspiration confirmed the presence of bacterial infection, all patients underwent prompt arthroscopic treatment, which consisted of drainage, lavage, and debridement. Postoperatively, patients were given 2 to 6 weeks of intravenous antibiotics, followed by long-term oral antibiotic suppression. At a mean follow-up of 70 months (range, 29-104 months), no recurrence of infection occurred. No progressive radiographic loosening was noted. Based on this initial study, we believe that arthroscopic irrigation and debridement can benefit well-selected patients who suffer late, acute hip periprosthetic infections. Effective treatment requires early diagnosis, prompt arthroscopic debridement, well-fixed components, a sensitive microorganism, and patient tolerance to and compliance with the antibiotic therapy.

Acute Disease↗
PubMed1999

Coculture system to assess biocompatibility of candidate orthopaedic materials.

When examining the biocompatibility of materials for orthopaedic use, it is important to examine the in vitro response of osteoblasts and macrophages to the material. The purpose of the current study was to develop an in vitro system that more accurately models the dynamic macrophage and osteoblast interactive response to biomaterials. A filter coculture system was designed that enables two cell types to be separated, while permitting cellular mediators to diffuse through its porous membrane. Using the filter coculture system, macrophage and osteoblast interaction in response to polymethylmethacrylate particle exposure was examined. As a marker of bone resorption potential, the level of prostaglandin E2 released from the macrophage and osteoblast coculture was compared with traditionally used in vitro culture systems. Cells interacting in the filter coculture system were found to produce prostaglandin E2 levels significantly greater than those of traditional conditioned media transfer systems. This filter coculture system offers an in vitro model that accounts for the continual cell to cell mediator interaction of two cell types simultaneously exposed to an implant material. This system may be useful in examining the biocompatibility of candidate materials at the bone interface, and thus elucidating the mechanisms of material induced bone resorption.

Animals↗
PubMed1999

Tissue engineering: orthopedic applications.

Because of an aging population and increased occurrence of sports-related injuries, musculoskeletal disorders have become one of the major health concerns in the United States. Current treatments, although fairly successful, do not provide the optimum therapy. These treatments typically rely on donor tissues obtained either from the patient or from another source. The former raises the issue of supply, whereas the latter poses the risk of rejection and disease transfer. This has prompted orthopedic surgeons and scientists to look for viable alternatives. In recent years, tissue engineering has gained increasing support as a method to treat orthopedic disorders. Because it uses principles of engineering, biology, and chemistry, tissue engineering may provide a more effective approach to the treatment of musculoskeletal disorders than traditional methods. This chapter presents a review of current methods and new tissue-engineering techniques for the treatment of disorders affecting bone, ligament, and cartilage.

Animals↗