The impact of hyaluronic acid oligomer content on physical, mechanical, and biologic properties of divinyl sulfone-crosslinked hyaluronic acid hydrogels.

In recent studies, we showed that exogenous hyaluronic acid oligomers (HA-o) stimulate functional endothelialization, though native long-chain HA is more bioinert and possibly more biocompatible. Thus, in this study, hydrogels containing high molecular weight (HMW) HA (1 x 10(6) Da) and HA-o mixtures (HA-o: 0.75-10 kDa) were created by crosslinking with divinyl sulfone (DVS). The incorporation of HA-o was found to compromise the physical and mechanical properties of the gels (rheology, apparent crosslinking density, swelling ratio, degradation) and to very mildly enhance inflammatory cell recruitment in vivo; increasing the DVS crosslinker content within the gels in general, had the opposite effect, though the relatively high concentration of DVS within these gels (necessary to create a solid gel) also stimulated a mild subcutaneous inflammatory response in vivo and VCAM-1 expression by endothelial cells (ECs) cultured atop; ICAM-expression levels remained very low irrespective extent of DVS crosslinking or HA-o content. The greatest EC attachment and proliferation (MTT assay) was observed on gels that contained the highest amount of HA-o. The study shows that the beneficial EC response to HA-o and biocompatibility of HA is mostly unaltered by their chemical derivatization and crosslinking into a hydrogel. However, the study also demonstrates that the relatively high concentrations of DVS, necessary to create solid gels, compromise their biocompatibility. Moreover, the poor mechanics of even these heavily crosslinked gels, in the context of vascular implantation, necessitates the investigation of other, more appropriate crosslinking agents. Alternately, the outcomes of this study may be used to guide an approach based on chemical immobilization and controlled surface-presentation of both bioactive HA-o and more biocompatible HMW HA on synthetic or tissue engineered grafts already in use, without the use of a crosslinker, so that improved, predictable, and functional endothelialization can be achieved, and the need to create a mechanically compliant biomaterial for standalone use, circumvented.

Prophylaxis of heterotopic ossification - an updated review.

Heterotopic ossification (HO) is defined as the process by which trabecular bone forms outside of the skeletal structure, occupying space in soft tissue where it does not normally exist. The current popular prophylactic treatment modalities include non-steroidal anti-inflammatory drugs (NSAIDs) and radiation therapy, although the literature remains inconclusive as to which is superior. Additionally, both treatments can lead to adverse effects to the patient. Recently there have been several studies attempting to identify new aspects of the etiology of heterotopic bone formation and introduce new prophylactic modalities with increased efficacy and fewer side effects. For this review, we selectively retrieved articles from Medline published from 1958-2008 on the prophylaxis of HO with the aim of assisting readers in quickly grasping the current status of research and clinical aspects of HO prophylaxis.

Platelet-rich and platelet-poor plasma: development of an animal model to evaluate hemostatic efficacy.

Hemostasis is important for any surgical procedure. One method uses autologous platelet-rich and/or platelet-poor plasma sprayed on the wound site. Although effective, there are little quantitative data available to fully document the extent to which these autologous products function as hemostats. Also, limitations in current animal models make quantitative study of topical hemostats difficult. A porcine partial-thickness skin wound model was developed to compare the hemostatic ability of these treatments with untreated control wounds. Rectangular partial-thickness dermal wounds were created in the back of a pig, which was then sprayed with activated platelet-rich plasma, activated platelet-poor plasma, or left untreated. Bleeding was quantified by two methods: 1) gravimetric measurement of exudate transfer to a sponge over a 15-minute interval, and 2) iron assay of the exudate over this same interval. Values for treated wounds were normalized to those of control wounds to minimize interanimal variability. Both gravimetric and iron assay measurements demonstrated that platelet-rich plasma was effective within 5 minutes after application with normalized bleeding values of approximately 35% and 20%, respectively, of the untreated controls. Corresponding values for platelet-poor plasma were approximately 90% and 65%, respectively, with differences only significant for the iron assay method measured on 10- and 15-minute wound exudate. Although both platelet-rich and platelet-poor plasma demonstrated hemostatic potential, the effect was more robust with the former. Iron assay was a more accurate method of measuring bleeding than gravimetric analysis.

Arterial embolization using poly-N-acetyl glucosamine gel in a rat kidney model.

Aqueous solutions of poly-N-acetyl glucosamine (p-GlcNAc) exhibit a liquid-gel transition at physiological pH and temperature. This feature inspired the authors to conduct a study to evaluate the macro- and histological changes of rat kidneys after embolization using either p-GlcNAc gel injection into the renal artery or ligation of the renal artery. The procedures were performed in 46 rats through open abdominal surgeries. Animals were sacrificed at 3 days and at 1, 3, 5, and 8 weeks postoperatively. The results of both macro-observation and histological study showed that p-GlcNAc gels were effective in causing necrosis and subsequent fibrosis in all embolized kidneys. The data indicate that p-GlcNAc gel may have promise as an effective agent for therapeutic embolization.

Vitreous preservation of articular cartilage grafts.

Articular cartilage has proved refractory to satisfactory cryopreservation using conventional freezing methods. Therefore, an ice-free cryopreservation method by vitrification was tested. Osteochondral plugs from New Zealand White rabbits were preserved using either a freezing method or an ice-free vitrification method of cryopreservation. Preserved and fresh control plugs were implanted in the tibial plateau of allogeneic recipients. A modified O'Driscoll grading scale, based on gross pathology, histopathology, and histochemistry, was used to evaluate the explants.The histology of fresh and vitrified explants was essentially the same, while the frozen cryopreserved explants were devoid of chondrocytes and only fibroblastlike cells were observed. The O'Driscoll grading indicated that both fresh and vitrified plugs performed significantly better than frozen plugs (p < or =.05). The results demonstrate the feasibility of vitrification as a storage method for cartilaginous tissues.