The evaluation of two new hyaluronan hydrogels as nasal dressing in the rabbit maxillary sinus.

Background: The postoperative scaring, ostial stenosis, and adhesions after functional endoscopic sinus surgery for chronic rhinosinusitis remains a major problem. This study was designed to evaluate two new hyaluronan (HA) hydrogels for neo-ostium antistenosis and promoting wound healing in a rabbit maxillary sinus model.

Methods: The anterior wall of the maxillary sinus of 48 rabbits was removed to create a 4-mm circumferential wound both on the nasal and on the sinus sides.

Effect of gelatin on heparin regulation of cytokine release from hyaluronan-based hydrogels.

The hypothesis that incorporation of small amounts (0.3% w/w) of modified heparin in thiol-modified hyaluronan or HA and gelatin hydrogels would regulate release of cytokine growth factors (GFs) from those gels has been investigated in vitro. In addition, the physiologic response to gel implantation has been evaluated in vivo.

Prevention of peritendinous adhesions using a hyaluronan-derived hydrogel film following partial-thickness flexor tendon injury.

Peritendinous adhesions are an important complication of flexor tendon injury. Three hyaluronan (HA)-derived biomaterials were evaluated for the reduction of peritendinous adhesions following partial-thickness tendon injury in rabbits. Rabbits (n = 24) were divided into three groups (n = 8 per group), which were used for gross evaluation, histologic assessment, or biomechanical testing.

Structural variations in a single hyaluronan derivative significantly alter wound-healing effects in the rabbit maxillary sinus.

Background: Biomaterials based on hyaluronan (HA) are currently used after sinus surgery but have not been found to decrease scarring or enhance wound healing. Chemical composition of these modified HA molecules may impact their biological and clinical effects.

Objective: To analyze chemical variations of a single crosslinked HA-based hydrogel, chemically modified thiolated HA (CMHA-SX).

Tumor engineering: orthotopic cancer models in mice using cell-loaded, injectable, cross-linked hyaluronan-derived hydrogels.

Current cancer xenograft models used to evaluate new anticancer therapies are limited to "good take" cell lines, fail to mimic normal human disease, and poorly predict clinical outcomes. We now describe the use of an injectable, in situ cross-linkable synthetic extracellular matrix (sECM) to deliver and grow cancer cells in vivo. The hyaluronan (HA)-derived sECMs were seeded with breast, colon, and ovarian cancer cells prior to gelation, and then injected subcutaneously into mammary fat pads, subserosally in colons, and intracapsularly in ovaries, respectively.

Osteochondral defect repair with autologous bone marrow-derived mesenchymal stem cells in an injectable, in situ, cross-linked synthetic extracellular matrix.

A co-cross-linked synthetic extracellular matrix (sECM) composed of chemically modified hyaluronic acid and gelatin was used as a cell delivery vehicle for osteochondral defect repair in a rabbit model. A full-thickness defect was created in the patellar groove of the femoral articular cartilage in each of 2 rabbit joints, and 4 experimental groups were assigned (12 rabbits/group): untreated control, autologous mesenchymal stem cells (MSCs) only, sECM only, and MSCs + sECM. The sECM hydrogels were allowed to cross-link in the defect in situ.

Effect of a synthetic extracellular matrix on vocal fold lamina propria gene expression in early wound healing.

An improved understanding of molecular response in the vocal folds to a synthetic extracellular matrix (sECM) during early wound repair is essential for understanding functional improvement of the tissue and implementation of future tissue-engineering strategies. The present study used real-time reverse transcriptase polymerase chain reaction to measure transcript expression of selected markers (procollagen alpha 2 type I, fibronectin, fibromodulin, hyaluronan synthase 2, and hyaluronidase 2) in 20 rabbits that underwent vocal fold biopsy bilaterally. After the biopsy, Carbylan-GSX 5% was injected immediately into the left vocal fold, and saline was injected into the right vocal fold.

Release of basic fibroblast growth factor from a crosslinked glycosaminoglycan hydrogel promotes wound healing.

We describe synthetic extracellular matrix (sECM) hydrogel films composed of co-crosslinked thiolated derivatives of chondroitin 6-sulfate (CS) and heparin (HP) for controlled-release delivery of basic fibroblast growth factor (bFGF) to full-thickness wounds in genetically diabetic (db/db) mice. In this model for chronic wound repair, full-thickness wounds were treated with CS, CS-bFGF, or CS-HP-bFGF films. At 2 and 4 weeks postinjury, wound closure and formation of the new epidermis and dermis were determined.

Influence of cross-linked hyaluronic acid hydrogels on neurite outgrowth and recovery from spinal cord injury.

Object: Therapies that use bioactive materials as replacement extracellular matrices may hold the potential to mitigate the inhibition of regeneration observed after central nervous system trauma. Hyaluronic acid (HA), a nonsulfated glycosaminoglycan ubiquitous in all tissues, was investigated as a potential neural tissue engineering matrix.

Methods: Chick dorsal root ganglia were cultured in 3D hydrogel matrices composed of cross-linked thiol-modified HA or fibrin.

Reduced postoperative intra-abdominal adhesions using Carbylan-SX, a semisynthetic glycosaminoglycan hydrogel.

Objective: To compare the efficacy of crosslinked Carbylan-SX (Carbylan BioSurgery, Inc., Palo Alto, CA) hydrogel films and sprayable gels as physical barriers in reducing postoperative intra-abdominal adhesions in the rat cecum-abdominal wall and rat uterine horn models.

Design: Pre-formed crosslinked Carbylan-SX films and sprayable in situ crosslinkable Carbylan-SX gels were evaluated in rat cecum-abdominal wall and rat uterine horn models and compared with commercially available and clinically used Seprafilm.

Crosslinked hydrogels for tympanic membrane repair.

Problem: To provide a less expensive and more convenient protocol for the treatment of tympanic membrane perforations (TMPs).

Methods: Several materials were prepared and compared for TMP repair including Carbylan-SX, Gelatin-DTPH-PEGDA (GX), Carbylan-S/Gelatin-DTPH (Carbylan-GSX) (injectable and sponge), Gelfoam, Epifilm, and crosslinked thiolated chondroitin sulfate (CS-DTPH-PEGDA [CS-SX]). Hartley pigmented guinea pigs (Elm Hill) underwent bilateral myringotomy with 1 ear left as a control and the other treated with one of the previously mentioned materials.

Cross-linked hydrogels for middle ear packing.

Objective: To develop an ideal supportive packing material for ossiculoplasty, tympanoplasty, or other otologic procedures.

Materials And Methods: Several materials, namely, Carbylan-SX (P-C; Sentrx Surgical, Inc., Salt Lake City, UT), Gelfoam (P-GF; Pharmacia & Upjohn, Kalamazoo, MI), and Merogel (P-MG; Medtronics, Inc.

Vocal fold tissue repair in vivo using a synthetic extracellular matrix.

Chemically modified hyaluronic acid (HA)-gelatin hydrogels have been documented to support attachment, growth, and proliferation of fibroblasts in vitro and to facilitate repair and engineering of tissues in vivo. The objective of this study was to determine the optimal composition of a synthetic extracellular matrix (sECM) that would promote wound repair and induce tissue regeneration in a rabbit vocal fold wound healing model. The sECM was formed using a thiol-modified semisynthetic glycosaminoglycan (GAG) derived of HA (Carbylan-SX) mixed with a thiolated gelatin derivative, co-cross-linked with poly(ethylene glycol) diacrylate to form Carbylan-GSX.

Stimulation of in vivo angiogenesis using dual growth factor-loaded crosslinked glycosaminoglycan hydrogels.

Crosslinked, chemically modified hyaluronan (HA) hydrogels pre-loaded with two cytokine growth factors, vascular endothelial growth factor (VEGF) and angiopoietin-1 (Ang-1), were employed to elicit new microvessel growth in vivo, in both the presence and absence of heparin (Hp) in the gels. HA hydrogel film samples were surgically implanted in the ear pinnae of mice, and the ears were harvested at 7 or 14 days post-implantation. Analysis of neovascularization showed that each of the treatment groups receiving an implant, except for HA/Hp at day 14, demonstrated significantly more microvessel density than control ears undergoing surgery but receiving no implant (p<0.

Synthesis and evaluation of injectable, in situ crosslinkable synthetic extracellular matrices for tissue engineering.

Simple and effective biocompatible materials that mimic the natural extracellular matrix (ECM) were developed for a variety of uses in regenerative medicine. These synthetic ECMs (sECMs) were designed to recapitulate the minimal composition required to obtain functional ECMs. The sECM components are crosslinkable in situ, and may be seeded with cells prior to injection in vivo, without compromising either the cells or the recipient tissues.

Cross-linked hyaluronan-coated stents in the prevention of airway stenosis.

Objective: This project studies the use of airway stents coated with a cross-linked derivative of hyaluronan (HA) in a rabbit airway model of subglottic stenosis (SGS).

Study Design And Setting: An acute subglottic mucosal injury and airway stent placement design were used in a rabbit model. Thirty-six rabbits were randomized to 6 different study groups.

Heparin-regulated release of growth factors in vitro and angiogenic response in vivo to implanted hyaluronan hydrogels containing VEGF and bFGF.

Controlled release of human vascular endothelial growth factor (VEGF) or basic fibroblast growth factor (bFGF) from hydrogels composed of chemically modified hyaluronan (HA) and gelatin (Gtn) was evaluated both in vitro and in vivo. We hypothesized that inclusion of small quantities of heparin (Hp) in these gels would regulate growth factor (GF) release over an extended period, while still maintaining the in vivo bioactivity of released GFs. To test this hypothesis, HA, Gtn, and Hp (15 kDa) were modified with thiol groups, then co-crosslinked with poly (ethylene glycol) diacrylate (PEGDA).

Aminooxy pluronics: synthesis and preparation of glycosaminoglycan adducts.

Novel biomaterials have been prepared in which glycosaminoglycans (GAGs) are chemically modified to create amphiphilic multiblock copolymers that are able to adhere to hydrophobic surfaces and can self-assemble into cross-linker-free hydrogels. First, the triblock poly(ethylene oxide)-polypropylene oxide copolymers (Pluronics) were converted into the previously unknown aminooxy (AO) derivatives. Both mono-AO and bis-AO Pluronics (AOPs) were synthesized and fully characterized in order to prepare tetrablock and pentablock copolymers, respectively.

Molecular stenting with a crosslinked hyaluronan derivative inhibits collagen gel contraction.

Adult burn wounds, which lack hyaluronan (HA), often undergo excessive tissue remodeling and contraction. In contrast fetal wounds, which contain large amounts of HA, undergo remodeling that culminates in a scarless repair or regeneration. Therefore, adding a HA derivative to burn wounds would better mimic the fetal extracellular matrix and could reduce contraction.

Accelerated repair of cortical bone defects using a synthetic extracellular matrix to deliver human demineralized bone matrix.

Injectable hydrogel and porous sponge formulations of Carbylan-GSX, a crosslinked synthetic extracellular matrix (ECM), were used to deliver human demineralized bone matrix (DBM) in a rat femoral defect model. A cortical, full-thickness 5-mm defect was created in two femurs of each rat. Six rats were assigned to each of five experimental groups (thus, 12 defects per group).

Composition of hyaluronan affects wound healing in the rabbit maxillary sinus.

Background: Hyaluronan (HA) is a ubiquitous component of the extracellular matrix. HA and its derivatives have been used in the sinuses to reduce scarring and possibly promote wound healing. However, in recent animal studies, HA esters exhibited inflammatory effects.

Fibronectin functional domains coupled to hyaluronan stimulate adult human dermal fibroblast responses critical for wound healing.

Fibronectin (FN) facilitates dermal fibroblast migration during normal wound healing. Proteolytic degradation of FN in chronic wounds hampers healing. Previously, three FN functional domains (FNfd) have been shown to be sufficient for optimal adult human dermal fibroblast migration.