Xenotransplantation in orthopaedic surgery.

We define xenotransplantation as including any procedure that involves the transplantation, implantation, or infusion into a human recipient of cells, tissues, or organs from a nonhuman animal source or of human body fluids, cells, tissues, or organs that have had ex vivo contact with nonhuman animal cells, tissues, or organs. The current FDA definition of xenotransplantation relates to procedures involving live, nonhuman materials. The proposed use of xenotransplanted tissues for treatment of a wide variety of human diseases is increasing.

Solvent/non-solvent sintering: a novel route to create porous microsphere scaffolds for tissue regeneration.

Solvent/non-solvent sintering creates porous polymeric microsphere scaffolds suitable for tissue engineering purposes with control over the resulting porosity, average pore diameter, and mechanical properties. Five different biodegradable biocompatible polyphosphazenes exhibiting glass transition temperatures from -8 to 41 degrees C and poly (lactide-co-glycolide), (PLAGA) a degradable polymer used in a number of biomedical settings, were examined to study the versatility of the process and benchmark the process to heat sintering. Parameters such as: solvent/non-solvent sintering solution composition and submersion time effect the sintering process.

Biphasic scaffold for annulus fibrosus tissue regeneration.

Intervertebral disc (IVD) degeneration is the major cause of lower back pain, while the currently available treatments are symptomatic rather than curative. Tissue engineering is a powerful therapeutic strategy that can restore the normal biomechanical motion of the human spine. The ability of a biphasic elastic scaffold to structurally and elastically simulate the annulus fibrosus (AF) tissue of the IVD was explored.

Development of injectable thermogelling chitosan-inorganic phosphate solutions for biomedical applications.

Thermosetting polymers are attractive candidates for biomedical applications as noninvasive therapeutic delivery vehicles. In the present study, the feasibility of developing a neutral physiological temperature setting injectable formulation based on chitosan and an inorganic phosphate salt have been demonstrated. The in situ gelling system was developed by adding different concentrations of ammonium hydrogen phosphate (AHP) to chitosan solution.

Mouse growth and differentiation factor-5 protein and DNA therapy potentiates intervertebral disc cell aggregation and chondrogenic gene expression.

Background Context: Growth and differentiation factor-5 (GDF-5)-deficient mice showed abnormalities in intervertebral disc (IVD) structure and extracellular matrix. Adenovirus-mediated GDF-5 delivery can promote the growth of rabbit disc cells.

Purpose: The aim of the present study was to investigate the effect of recombinant GDF-5 protein and GDF-5 complementary DNA (cDNA) on the metabolism of IVD cells.

Miscibility and in vitro osteocompatibility of biodegradable blends of poly[(ethyl alanato) (p-phenyl phenoxy) phosphazene] and poly(lactic acid-glycolic acid).

Previously we demonstrated the ability of ethyl glycinato substituted polyphosphazenes to neutralize the acidic degradation products and control the degradation rate of poly(lactic acid-glycolic acid) (PLAGA) by blending. In this study, blends of high strength poly[(50% ethyl alanato) (50% p-phenyl phenoxy) phosphazene] (PNEA(50)PhPh(50)) and 85:15 PLAGA were prepared using a mutual solvent approach. Three different solvents, methylene chloride (MC), chloroform (CF) and tetrahydrofuran (THF) were studied to investigate solvent effects on blend miscibility.

Apatite nano-crystalline surface modification of poly(lactide-co-glycolide) sintered microsphere scaffolds for bone tissue engineering: implications for protein adsorption.

A number of bone tissue engineering approaches are aimed at (i) increasing the osteconductivity and osteoinductivity of matrices, and (ii) incorporating bioactive molecules within the scaffolds. In this study we examined the growth of a nano-crystalline mineral layer on poly(lactide-co-glycolide) (PLAGA) sintered microsphere scaffolds for tissue engineering. In addition, the influence of the mineral precipitate layer on protein adsorption on the scaffolds was studied.

Novel biodegradable poly(1,8-octanediol malate) for annulus fibrosus regeneration.

A novel elastic scaffold that simulates the deformability of annulus fibrosus (AF) and has good biocompatibility was developed. The scaffold was formed of a malic acid-based polyester poly(1,8-octanediol malate) (POM), which was synthesized by direct polycondensation. The tensile strength of POM gradually increased with the extension of the polymerization time, while the degradation rate decreased.

Amorphous hydroxyapatite-sintered polymeric scaffolds for bone tissue regeneration: physical characterization studies.

Given the inherent shortcomings of autografts and allografts, donor-site morbidity and risk of disease transmission, respectively, alternatives to traditional bone grafting options are warranted. To this end, poly(lactide-co-glycolide) (PLAGA) and in situ-synthesized amorphous hydroxyapatite (HA) were used to construct three-dimensional microsphere-based composite scaffolds of varying HA content for bone regeneration. In the current study, the effect of adding amorphous HA to the PLAGA scaffolds on their physical characteristics and in vitro degradation mechanism was investigated.

Human endothelial cell growth and phenotypic expression on three dimensional poly(lactide-co-glycolide) sintered microsphere scaffolds for bone tissue engineering.

Bone tissue engineering offers promising alternatives to repair and restore tissues. Our laboratory has employed poly(lactide-co-glycolide) PLAGA microspheres to develop a three dimensional (3-D) porous bioresorbable scaffold with a biomimetic pore structure. Osseous healing and integration with the surrounding tissue depends in part on new blood vessel formation within the porous structure.

Biomimetic tissue-engineered anterior cruciate ligament replacement.

There are >200,000 anterior cruciate ligament (ACL) ruptures each year in the United States, and, due to the poor healing properties of the ACL, surgical reconstruction with autograft or allograft tissue is the current treatment of these injuries. To regenerate the ACL, the ideal matrix should be biodegradable, porous, and exhibit sufficient mechanical strength to allow formation of neoligament tissue. Researchers have developed ACL scaffolds with collagen fibers, silk, biodegradable polymers, and composites with limited success.

Miscibility of bioerodible polyphosphazene/poly(lactide-co-glycolide) blends.

We have previously demonstrated the feasibility of blending bioerodible polyphosphazenes with poly(lactide-co-glycolide) (PLGA) to form versatile polymeric materials with altered bioerosion properties. These studies demonstrated the effective neutralization of the acidic degradation products of PLGA by the polyphosphazene hydrolysis products. In the present study, five new polymers of dipeptide polyphosphazenes poly[(ethyl glycinato)x(glycyl-ethyl glycinato)yphosphazene] and novel blends of these polyphosphazenes with poly(lactide-co-glycolide) (PLGA) were synthesized and fabricated.

Novel low temperature setting nanocrystalline calcium phosphate cements for bone repair: osteoblast cellular response and gene expression studies.

Low temperature setting calcium phosphate cements (CPC) formed from reactive calcium phosphate precursors are receiving great attention in the fields of orthopaedics and tissue engineering. The purpose of this study was to evaluate the mechanical properties and osteocompatibility of a novel calcium deficient hydroxyapatite (CDSHA) with a Ca/P ratio of 1.6 developed in our laboratories and compare it to a previously developed calcium deficient hydroxyapatite (CDHA) with a Ca/P ratio of 1.

Synthesis, characterization of chitosans and fabrication of sintered chitosan microsphere matrices for bone tissue engineering.

The objective of the present study was to synthesize and characterize chitosans with different degrees of deacetylation (DDA%), prepare chitosan microspheres with controlled chemistry and geometry, and fabricate three-dimensional (3-D) chitosan matrices based on microspheres with appropriate pore size, porosity and mechanical properties suitable for bone tissue engineering applications. Chitosans with three DDA% of 69%, 79% and 97% were obtained using a thermomechanochemical technique by varying the applied pressure and NaOH solution concentration. The prepared chitosans were comprehensively characterized by proton nuclear magnetic resonance, elemental analysis, viscosity measurements, thermal analyses and X-ray diffraction.

Novel tubular composite matrix for bone repair.

Tissue engineering develops organ replacements to overcome the limitations associated with autografts and allografts. The work presented here details the development of biodegradable, porous, three-dimensional polymer-ceramic-sintered microsphere matrices to support bone regeneration. Poly(lactide-co-glycolide)/hydroxyapatite microspheres were formed using solvent evaporation technique.

Tissue engineering of the anterior cruciate ligament using a braid-twist scaffold design.

The anterior cruciate ligament (ACL) is the most commonly injured intra-articular ligament of the knee. The insufficient vascularization of this tissue prevents it from healing completely after extreme tearing or rupture, creating a need for ACL grafts for reconstruction. The limitations of existing grafts have motivated the investigation of tissue-engineered ACL grafts.

Polymers as biomaterials for tissue engineering and controlled drug delivery.

The advent of biodegradable polymers has significantly influenced the development and rapid growth of various technologies in modern medicine. Biodegradable polymers are mainly used where the transient existence of materials is required and they find applications as sutures, scaffolds for tissue regeneration, tissue adhesives, hemostats, and transient barriers for tissue adhesion, as well as drug delivery systems. Each of these applications demands materials with unique physical, chemical, biological, and biomechanical properties to provide efficient therapy.

Osteogenic differentiation of adipose-derived stromal cells treated with GDF-5 cultured on a novel three-dimensional sintered microsphere matrix.

Background Context: It is well known that under the proper conditions multipotential bone marrow stromal cells are capable of osteogenic differentiation. Recently studies have demonstrated that an analogous subpopulation of cells exist within adipose tissue. Although early studies characterizing these adipose-derived stromal (ADS) cells in culture exist, investigations exploring the characteristics and viability of these cells cultured on a three-dimensional sintered microsphere matrix are absent.

Polymeric nanofibers as novel carriers for the delivery of therapeutic molecules.

Nanotechnology and nanoscience are relatively new technological endeavors that encompass the study, control, manipulation, and assembly of multifarious nanoscale components into materials, systems and devices to serve human interest and needs. Among the various currently used nanostructures for high technology applications polymeric nanofibers have received immense interest due to the ease of fabrication, controllable size/shape, and properties. Polymeric nanofibers have been extensively investigated for diversified applications, including filtration, barrier fabrics, wipes, personal care, biomedical, and pharmaceutical applications.

Nanobiomaterial applications in orthopedics.

Advancements in nanobiotechnology are revolutionizing our capability to understand biological intricacies and resolve biological and medical problems by developing subtle biomimetic techniques. Nanocomposites and nanostructured materials are believed to play a pivotal role in orthopedic research since bone itself is a typical example of a nanocomposite. This article reviews current strategies using nanobiomaterials to improve current orthopedic materials and examines their applications in bone tissue engineering.

A preliminary report on a novel electrospray technique for nanoparticle based biomedical implants coating: precision electrospraying.

The compatibility and biological efficacy of biomedical implants can be enhanced by coating their surface with appropriate agents. For predictable functioning of implants in situ, it is often desirable to obtain an extremely uniform coating thickness without effects on component dimensions or functions. Conventional coating techniques require rigorous processing conditions and often have limited adhesion and composition properties.

Fibroblast growth factor 2 induced proliferation in osteoblasts and bone marrow stromal cells: a whole cell model.

Fibroblast growth factor 2 (FGF2) can enhance the proliferative capacity of bone and bone marrow stromal cells; however, the mechanisms behind this effect are not well described. We present a whole-cell kinetic model relating receptor-mediated binding, internalization, and processing of FGF2 to osteoblastic proliferative response. Focusing on one of the potential signaling complex stoichiometries, we utilized experimentally measured and modeled estimated rate constants to predict in vitro proliferation and distinguish between potential binding orders.

Bone tissue engineering by gene delivery.

Recombinant human bone morphogenetic protein-2 and -7 were recently granted United States Food and Drug Administration approval for select clinical applications in bone repair. While significant progress has been made in the delivery of recombinant osteogenic factor to promote bone healing, the short half-life and instability of the protein requires the delivery of milligram quantities of factor or multiple dosages. The potential of gene therapy for bone regeneration is the delivery of physiological levels of therapeutic protein using natural cellular mechanisms.