John F. Caccamese

Macroporous hydrogels upregulate osteogenic signal expression and promote bone regeneration.

The objective of this work was to investigate the effects of macroporous hydrogel architecture on the osteogenic signal expression and differentiation of human mesenchymal stem cells (hMSCs). In particular, we have proposed a tissue engineering approach for orbital bone repair based on a cyclic acetal biomaterial formed from 5-ethyl-5-(hydroxymethyl)-beta,beta-dimethyl-1,3-dioxane-2-ethanol diacrylate (EHD) and poly(ethylene glycol) diacrylate (PEGDA). The EHD monomer and PEGDA polymer may be fabricated into macroporous EH-PEG hydrogels by radical polymerization and subsequent porogen leaching, a novel technique for hydrophilic gels. We hypothesized that EH-PEG hydrogel macroporosity facilitates intercellular signaling among hMSCs. To investigate this phenomenon, hMSCs were loaded into EH-PEG hydrogels with varying pore size and porosity. The viability of hMSCs, the expression of bone morphogenetic protein-2 (BMP-2), BMP receptor type 1A, and BMP receptor type 2 by hMSCs, and the differentiation of hMSCs were then assessed. Results demonstrate that macroporous EH-PEG hydrogels support hMSCs and that this macroporous environment promotes a dramatic increase in BMP-2 expression by hMSCs. This upregulation of BMP-2 expression is associated by a more rapid hMSC differentiation, as measured by alkaline phosphatase expression. Altering hMSC interactions with the EH-PEG hydrogel surface, by the addition of fibronectin, did not appear to augment BMP-2 expression. We therefore speculate that EH-PEG hydrogel macroporosity facilitates autocrine and paracrine signaling by localizing endogenously expressed factors within the hydrogels pores and thus promotes hMSC osteoblastic differentiation and bone regeneration.

Noggin inhibits postoperative resynostosis in craniosynostotic rabbits

Inhibition of bone formation after surgery to correct craniosynostosis would alleviate the need for secondary surgeries and decrease morbidity and mortality. This study used a single dose of Noggin protein to prevent resynostosis and improve postoperative outcomes in a rabbit model of craniosynostosis.

Venous Anastomoses Using Microvascular Coupler in Free Flap Head and Neck Reconstruction

PURPOSE This study is a retrospective review of the experience using the venous coupler for head and neck reconstruction over a 3-year period at the University of Maryland Medical Center, Department of Oral and Maxillofacial Surgery. MATERIALS AND METHODS One hundred seventy-eight consecutive cases of microvascular free flaps between May 2007 and September 2010 were retrospectively reviewed. Data were collected by demographic information, flap type, recipient vessels, method of anastomosis, coupler size, coupler orientation, complications associated with coupler, and reconstruction results. Fisher exact test was used for statistical analysis. RESULTS There were 294 anastomotic coupler devices used in 173 flaps, with hand-sewn venous anastomoses performed in 5 patients. The overall flap success rate was 94.9% (169/178). Success rate among cases in which the coupler was used was 95.4% (8/173). Total coupler venous thrombosis rate was 4.0% (7/173), with a statistically significant difference (P < .05) in reference to the number of venous anastomoses performed: 58 cases had a single vein anastomosed, 5 cases developed thrombosis; while the 115 flaps with 2 venous anastomoses, only 2 cases had thrombosis. CONCLUSIONS The microvascular coupler is reliable for venous anastomosis in free flap head and neck reconstruction; dual-vein anastomoses appear to have better results than single-vein anastomoses. Flow coupler has a promising utility in monitoring buried flaps and flaps that are difficult to observe. The microvascular coupler deserves to be more commonly used in free flap head and neck reconstruction.

Tissue response and orbital floor regeneration using cyclic acetal hydrogels

Orbital floor injuries are a common form of traumatic craniofacial injury that may not heal properly through the bodys endogenous response. Reconstruction is often necessary, and an optimal method does not exist. We propose a tissue engineering approach for orbital bone repair based upon a cyclic acetal biomaterial formed from 5-ethyl-5-(hydroxymethyl)-beta,beta-dimethyl-1,3-dioxane-2-ethanol diacrylate (EHD) and poly(ethylene glycol) diacrylate (PEGDA). The EHD monomer and PEGDA polymer may be fabricated into an EH-PEG hydrogel by radical polymerization. The objectives of this work were to study (1) the tissue response to EH-PEG hydrogels in an orbital bone defect and (2) the induction of bone formation by delivery of bone morphogenetic protein-2 (BMP-2) from EH-PEG hydrogels. EH-PEG hydrogels were fabricated and implanted into an 8-mm rabbit orbital floor defect. Experimental groups included unloaded EH-PEG hydrogels, and EH-PEG hydrogels containing 0.25 microg and 2.5 microg BMP-2/implant. Results demonstrated that the unloaded hydrogel was initially bordered by a fibrin clot and then by fibrous encapsulation. BMP-2 loaded EH-PEG hydrogels, independent of concentration, were surrounded by fibroblasts at both time points. Histological analysis also demonstrated that significant bone growth was present at the 2.5 microg BMP-2/implant group at 28 days. This work demonstrates that the EH-PEG construct is a viable option for use and delivery of BMP-2 in vivo.

Characterization of cyclic acetal hydroxyapatite nanocomposites for craniofacial tissue engineering

Cyclic acetal hydrogels are a novel group of biomaterials which may facilitate osteogenic differentiation of encapsulated bone marrow stromal cells (BMSCs) because of their neutral degradation products. Here, we have incorporated hydroxyapatite nanoparticles within cyclic acetal hydrogels to create cyclic acetal nanocomposites for craniofacial tissue engineering applications. We hypothesized that inclusion of nanosized hydroxyapatite particles within cyclic acetal hydrogels would upregulate osteogenic signal expression of encapsulated BMSCs, due to enhanced cell adhesion, and therefore promote osteodifferentiation. Experimental nanocomposite groups consisted of lower (5 ng/mL) and higher (50 ng/mL) concentrations of nanoparticles. The nanocomposites were characterized by scanning electron microscopy, transmission electron microscopy, and energy dispersive spectroscopy. Swelling parameters of hydrogels in the presence of nanoparticles was studied. Osteoblastic differentiation was characterized by alkaline phosphatase (ALP) and osteocalcin (OC) expression, whereas endogenous osteogenic signal expression was characterized by morphogenetic protein-2 (BMP-2) expression. Finally, immunohistochemistry was performed to detect the presence of OC at the protein level. Results indicated that hydroxyapatite nanoparticles were uniformly distributed throughout the hydrogels and did not affect material properties of the gels. Viability of cells was not affected by nanoparticle concentration, and BMP-2 and OC mRNA expression was enhanced in the presence of nanoparticles. However, a difference in BMP-2, ALP, and OC mRNA expression was not noted between the lower and higher concentrations of nanoparticles. This work demonstrates that inclusion of hydroxyapatite nanoparticles within a cyclic acetal nanocomposite hydrogel may enhance BMSC differentiation by promoting endogenous osteogenic signal expression.

Deep Neck Infections: Clinical Considerations in Aggressive Disease

Deep neck infections are common and occur as a consequence of several etiologies. Antibiotic therapy, interventional radiology, and patient support modalities have become increasingly sophisticated, although surgery continues to be the mainstay of treatment for most patients. Today, neck infections are rarely life threatening when sound and timely management is applied.

Analysis of an implantable venous anastomotic flow coupler: experience in head and neck free flap reconstruction.

Monitoring microvascular free flaps can present a difficult challenge. This is especially true in cases of buried or intra-oral free flaps. The authors conducted a retrospective review of 19 consecutive free flaps for head and neck reconstruction using a novel monitoring device, which combines a venous anastomotic coupler and an implantable microdoppler (Synovis Micro Companies Alliance Inc., Birmingham, AL, USA). 20 venous anastomoses were performed and monitored with the venous flow coupler device. Monitoring ranged from intra-operatively to postoperative day 7 (mean 4.2 days). Accurate flow signal interpretation was correct in 18 of 20 anastomoses (90%) but only 14 of the 20 coupled anastomoses (70%) were monitored for the complete period of time as desired by the surgeons. All 19 flaps survived. The venous anastomotic flow coupler appears to be a reliable adjunct to free flap monitoring and may help to improve it, with early detection of flap compromise and salvage.

Challenges Associated with Regeneration of Orbital Floor Bone

Orbital floor fractures are a serious consequence of craniofacial trauma and account for ∼60%-70% of all orbital fractures. Unfortunately, the bodys natural response to orbital floor defects generally may not restore proper function and facial aesthetics, which is complicated by the thin bone and adjacent sinuses. Current clinical treatments include alloplastic implants and autologous grafts; however, each has associated disadvantages and sequelae. This review has outlined necessary components for a successful tissue-engineered construct for orbital floor repair. In addition, current successes and progress in the literature specific to orbital floors and craniofacial research have been reviewed. Finally, challenges and future directions have been described.

Strength Analysis of 6 Resorbable Implant Systems: Does Heating Affect the Stress-Strain Curve?

PURPOSE The objective was to directly compare the strength of 6 different resorbable implant plating systems using an in vitro model before and after heating. MATERIALS AND METHODS Red oak wood was cut and fixated using various resorbable plates and screws. Vertical load was applied and the specimens fractured, while a test machine gathered data. This was repeated after heating of the specimens. RESULTS Several parameters were analyzed, and force versus displacement curves were plotted for each specimen. CONCLUSIONS There were no statistically significant differences for total maximum loads between heat-treated and non heat-treated specimens. There were differences in strengths amongst the various systems.

Blocking Bone Morphogenetic Protein Function Using In Vivo Noggin Therapy Does Not Rescue Premature Suture Fusion in Rabbits with Delayed-Onset Craniosynostosis

Background: Craniosynostosis is defined as the premature fusion of one or more cranial sutures. Bone morphogenetic proteins (BMPs), regulators of ossification, have been implicated in premature suture fusion. Noggin, an extracellular BMP inhibitor, has been shown experimentally to inhibit resynostosis following surgery. The present study was designed to test the hypothesis that BMP inhibition using noggin therapy may rescue sutures destined to fuse by inhibiting initial ossification. Methods: Twenty-six, 10-day old rabbits with familial, delayed-onset, coronal suture synostosis were randomly divided into three groups: (1) the sham surgical control group, (2) the bovine serum albumin–treated group [10 &mgr;g/suture (protein/vehicle controls)], and (3) the noggin therapy group (10 &mgr;g/suture; experimental group). Sutural growth was monitored by radiopaque markers implanted at 10 days of age. At 25 days, the bovine serum albumin or noggin was combined with a slow-resorbing collagen vehicle and injected subperiosteally above the coronal suture. Somatic and sutural growth data were collected at 10, 25, 42, and 84 days of age. Coronal sutures were harvested at 84 days to histologically assess fusion. Results: Results showed no significant (p > 0.05) differences in suture separation at any age. Suture fusion assessed by histomorphology did not differ among the three groups. Although previous data showed noggin to inhibit postoperative resynostosis in this craniosynostotic rabbit model, here there was no effect on initial suture fusion. Conclusion: These results suggest that in this rabbit model of craniosynostosis, BMPs do not play a role in the pathogenesis of craniosynostosis and only play a role in postoperative bony wound healing.