Spontaneous malignant transformation in craniomaxillofacial fibrous dysplasia.

Spontaneous malignant transformation in craniomaxillofacial fibrous dysplasia (FD) is extremely rare and its clinicopathological characteristics remain largely unknown. Here, we aimed to characterize the epidemiology and clinicopathological features of malignancies arising from preexisting FD by presenting data from a Chinese tertiary referral hospital and review of English and Chinese literatures. The craniomaxillofacial disease registry of Shanghai Ninth People's Hospital was searched and reviewed to collect relevant information for patients diagnosed as malignant transformation in craniomaxillofacial FD between January 1993 and December 2010. An English and Chinese literature review was conducted to retrieve pertinent cases published in the past 2 decades with preset inclusion criteria. All included cases were further analyzed with regard to associated clinical and pathological variables. Three cases with osteosarcoma arising from previous craniomaxillofacial FD were found at our institution and 35 other cases were identified by literature review. These uncommon entities usually occurred in adults with a mean age of 39.8 years and equal gender preponderance. Maxilla remained the most common sites for malignancies followed by mandible and zygoma. Most malignancies were diagnosed as osteosarcoma followed by fibrosarcoma, chondrosarcoma, and malignant fibrous histiocytoma. Radical resection alone or with postoperative radiotherapy/chemotherapy remains the main treatment strategy with unfavorable prognosis due to local recurrence and distant metastasis. Taken together, our findings might for the first time provide the comprehensive information regarding the epidemiology, clinicopathological features, treatment, and prognosis of malignancies in craniomaxillofacial FD. Further investigations are warranted to improve early diagnosis and proper treatment for these uncommon entities.

Resistance to infection of five different materials in a rat body wall model.

BACKGROUND: Infection occurs after approximately 1% of hernia repair procedures. The resistance to infection of the repair materials is therefore an important consideration. We evaluated the infection resistance of five different materials in a rat model of body wall repair, two of which, urinary bladder matrix (UBM-ECM) and Revive, were not previously evaluated in a controlled model of infection. MATERIALS AND METHODS: An inoculum of 1 × 10(8) colony forming units of Staphylococcus aureus was delivered to the wound site following implantation of an autograft, UBM-ECM, Proceed, Prolene, or Revive. Infection was monitored by white blood cell counts, body temperature, bacterial culture, and histomorphologic analysis of the implant site. RESULTS: Infection was shown in all groups through increased white blood cell count and body temperature. Animals with UBM-ECM returned to pre-surgery body temperature before all other groups. Substantial bacterial clearance was found in the autograft, UBM-ECM, and Prolene. Histomorphologic analysis showed evidence for persistent bacterial infection in Prolene, Proceed, and Revive 28 d after implantation, whereas the autograft and UBM-ECM appeared free of infection. The autograft showed a pyogranulomatous inflammatory reaction at 28 d while UBM-ECM was similar to uninfected controls. CONCLUSIONS: Superior infection resistance was shown by UBM-ECM compared with the other materials, which were substantially equivalent. Histomorphologic analysis clearly showed an increased ability to resist persistent bacterial infection for UBM-ECM. Our results suggest UBM-ECM may be useful as a repair material in areas of high risk for infection.

Nitro-Oleic Acid (NO2-OA) Release Enhances Regional Angiogenesis in a Rat Abdominal Wall Defect Model.

Ventral hernia is often addressed surgically by the placement of prosthetic materials, either synthetic or from allogeneic and xenogeneic biologic sources. Despite advances in surgical approaches and device design, a number of postsurgical limitations remain, including hernia recurrence, mesh encapsulation, and reduced vascularity of the implanted volume. The in situ controlled release of angiogenic factors from a scaffold facilitating abdominal wall repair might address some of these issues associated with suboptimal tissue reconstruction. Furthermore, a biocomposite material that combines the favorable mechanical properties achievable with synthetic materials and the bioactivity associated with xenogeneic tissue sources would be desirable. In this report, an abdominal wall repair scaffold has been designed based on a microfibrous, elastomeric poly(ester carbonate)urethane urea matrix integrated with a hydrogel derived from decellularized porcine dermis (extracellular matrix [ECM] gel) and poly(lactic-co-glycolic acid) (PLGA) microspheres loaded with nitro-oleic acid (NO2-OA). NO2-OA is an electrophilic fatty acid nitro-alkene derivative that, under hypoxic conditions, induces angiogenesis. This scaffold was utilized to repair a rat abdominal wall partial thickness defect, hypothesizing that the nitro-fatty acid release would facilitate increased angiogenesis at the 8-week endpoint. The quantification of neovascularization was conducted by novel methodologies to assess vessel morphology and spatial distribution. The repaired abdominal wall defects were evaluated by histopathologic methods, including quantification of the foreign body response and cellular ingrowth. The results showed that NO2-OA release was associated with significantly improved regional angiogenesis. The combined biohybrid scaffold and NO2-OA-controlled release strategy also reduced scaffold encapsulation, increased wall thickness, and enhanced cellular infiltration. More broadly, the three components of the composite scaffold design (ECM gel, polymeric fibers, and PLGA microparticles) enable the tuning of performance characteristics, including scaffold bioactivity, degradation, mechanics, and drug release profile, all decisive factors to better address current limitations in abdominal wall repair or other soft tissue augmentation procedures.

Timing effect of intramyocardial hydrogel injection for positively impacting left ventricular remodeling after myocardial infarction.

Intramyocardial injection of various injectable hydrogel materials has shown benefit in positively impacting the course of left ventricular (LV) remodeling after myocardial infarction (MI). However, since LV remodeling is a complex, time dependent process, the most efficacious time of hydrogel injection is not clear. In this study, we injected a relatively stiff, thermoresponsive and bioabsorbable hydrogel in rat hearts at 3 different time points - immediately after MI (IM), 3 d post-MI (3D), and 2 w post-MI (2W), corresponding to the beginnings of the necrotic, fibrotic and chronic remodeling phases. The employed left anterior descending coronary artery ligation model showed expected infarction responses including functional loss, inflammation and fibrosis with distinct time dependent patterns. Changes in LV geometry and contractile function were followed by longitudinal echocardiography for 10 w post-MI. While all injection times positively affected LV function and wall thickness, the 3D group gave better functional outcomes than the other injection times and also exhibited more local vascularization and less inflammatory markers than the earlier injection time. The results indicate an important role for injection timing in the increasingly explored concept of post-MI biomaterial injection therapy and suggest that for hydrogels with mechanical support as primary function, injection at the beginning of the fibrotic phase may provide improved outcomes.

Design of a Coupled Thermoresponsive Hydrogel and Robotic System for Postinfarct Biomaterial Injection Therapy.

BACKGROUND: In preclinical testing, ventricular wall injection of hydrogels has been shown to be effective in modulating ventricular remodeling and preserving cardiac function. For some approaches, early-stage clinical trials are under way. The hydrogel delivery method varies, with minimally invasive approaches being preferred. Endocardial injections carry a risk of hydrogel regurgitation into the circulation, and precise injection patterning is a challenge. An epicardial approach with a thermally gelling hydrogel through the subxiphoid pathway overcomes these disadvantages. METHODS: A relatively stiff, thermally responsive, injectable hydrogel based on N-isopropylacrylamide and N-vinylpyrrolidone (VP gel) was synthesized and characterized. VP gel thermal behavior was tuned to couple with a transepicardial injection robot, incorporating a cooling feature to achieve injectability. Ventricular wall injections of the optimized VP gel have been performed ex vivo and on beating porcine hearts. RESULTS: Thermal transition temperature, viscosity, and gelling time for the VP gel were manipulated by altering N-vinylpyrrolidone content. The target parameters for cooling in the robotic system were chosen by thermal modeling to support smooth, repeated injections on an ex vivo heart. Injections at predefined locations and depth were confirmed in an infarcted porcine model. CONCLUSIONS: A coupled thermoresponsive hydrogel and robotic injection system incorporating a temperature-controlled injectate line was capable of targeted injections and amenable to use with a subxiphoid transepicardial approach for hydrogel injection after myocardial infarction. The confirmation of precise location and depth injections would facilitate a patient-specific planning strategy to optimize injection patterning to maximize the mechanical benefits of hydrogel placement.

Tailoring the degradation rates of thermally responsive hydrogels designed for soft tissue injection by varying the autocatalytic potential.

The ability to modulate the degradation properties of biomaterials such as thermally responsive hydrogels is desirable when exploring new therapeutic strategies that rely on the temporary presence of a placed scaffold or gel. Here we report a method of manipulating the absorption rate of a poly(N-isopropylacrylamide) ((poly(NIPAAm)) based hydrogel across a wide range (from 1 d to 5 mo) by small alterations in the composition. Relying upon the autocatalytic effect, the degradation of poly(NIPAAm-co-HEMA-co-MAPLA), (HEMA = 2-hydroxyethyl methacrylate; MAPLA = methacrylate-polylactide) was greatly accelerated by adding a fourth monomer methacrylic acid (MAA) at no more than 2 mol% to obtain poly(NIPAAm-co-HEMA-co-MAPLA-co-MAA) (pNHMMj) where j reflects the MAA molar % in the reactant mixture. MAA residue introduction decreased the pH inside the hydrogels and in surrounding buffered solutions. Accelerated degradation positively correlated with MAA content in pNHMMj polymers, putatively by the accelerated cleavage of MAPLA residues to raise the transition temperature of the polymer above body temperature. Physical properties including thermal transition behavior and initial mechanical strength did not vary significantly with MAA content. A rat hindlimb injection model generally reflected the in vitro observation that higher MAA content resulted in more rapid degradation and cellular infiltration. The strategy of tuning the degradation of thermally responsive hydrogels where degradation or solubilization is determined by their polyester components might be applied to other tissue engineering and regenerative medicine applications where designed biomaterial degradation behavior is needed.

Histopathologic host response to polypropylene-based surgical mesh materials in a rat abdominal wall defect model.

Composite polypropylene-based surgical mesh materials including various synthetic polymers and naturally occurring biomaterials have been developed to ameliorate device-associated inflammatory response and associated reduced compliance of pure polypropylene meshes. This study evaluated the histomorphologic response of three composite polypropylene-based surgical meshes, Revive™, a polycarbonate polyurethane reinforced monofilamentous polypropylene scaffold, Assure™, a polycarbonate polyurethane reinforced monofilamentous polypropylene scaffold with a resorbable anti-adhesion layer of lactide caprolactone copolymer, and Proceed™, a polypropylene mesh modified with oxidized cellulose, in a soft tissue repair model in the rat. The host inflammatory response and neotissue formation were evaluated by semiquantitative histologic scoring including the amount of cellular infiltration, angiogenesis, presence of multinucleate giant cells, fibrous connective tissue formation, and host neo-extracellular matrix deposition for up to 26 weeks. All three composite surgical mesh materials showed good integration with host tissue as indicated by rapid cellular infiltration, abundant neo-vascularization, minimal shrinkage, and the lack of visible mesh degradation. The devices elicited a similar inflammatory response and the presence of a mild foreign body response in spite of the different composition and morphology of these composite mesh materials.