Implanted microvessels progress through distinct neovascularization phenotypes.

We have previously demonstrated that implanted microvessels form a new microcirculation with minimal host-derived vessel investment. Our objective was to define the vascular phenotypes present during neovascularization in these implants and identify post-angiogenesis events. Morphological, functional and transcriptional assessments identified three distinct vascular phenotypes in the implants: sprouting angiogenesis, neovascular remodeling, and network maturation. A sprouting angiogenic phenotype appeared first, characterized by high proliferation and low mural cell coverage. This was followed by a neovascular remodeling phenotype characterized by a perfused, poorly organized neovascular network, reduced proliferation, and re-associated mural cells. The last phenotype included a vascular network organized into a stereotypical tree structure containing vessels with normal perivascular cell associations. In addition, proliferation was low and was restricted to the walls of larger microvessels. The transition from angiogenesis to neovascular remodeling coincided with the appearance of blood flow in the implant neovasculature. Analysis of vascular-specific and global gene expression indicates that the intermediate, neovascular remodeling phenotype is transcriptionally distinct from the other two phenotypes. Therefore, this vascular phenotype likely is not simply a transitional phenotype but a distinct vascular phenotype involving unique cellular and vascular processes. Furthermore, this neovascular remodeling phase may be a normal aspect of the general neovascularization process. Given that this phenotype is arguably dysfunctional, many of the microvasculatures present within compromised or diseased tissues may not represent a failure to progress appropriately through a normally occurring neovascularization phenotype.

Gene expression in tissue associated with extracellular matrix modified ePTFE.

Previous studies have established that surface modification of ePTFE with extracellular matrix molecules promotes vascularization within and around the implanted material. To understand the molecular basis of this tissue response to modified ePTFE, we analyzed large-scale gene expression in nonmodified and extracellular matrix-modified ePTFE-associated healing. Using a microarray containing 15,000 unique mouse cDNAs and an ANOVA-based analysis, we identified 789 genes related to cell signaling, inflammation, matrix remodeling, and proliferation that were differentially expressed across time, between modifications, or both. Genes were clustered based upon similarity in gene expression, producing 7 unique temporal super-patterns of expression. The clustered data revealed 3 general expression patterns unique to tissue surrounding the nonmodified ePTFE, while 6 unique expression patterns were associated with extracellular matrix-modified ePTFE. The more diverse expression patterns associated with extracellular matrix-modified ePTFE suggests that the tissue surrounding the extracellular matrix-modified ePTFE is more dynamic in terms of transcriptional activity. Taken together, these clusters serve as a "genetic fingerprint" for tissue healing in response to a specific material or material modification. Use of these genetic profiles will aid in the pursuit of improved device biocompatibility and enhanced material function.

Arthroscopic bullet removal from the acetabulum.

Hip arthroscopy has been shown to offer minimally invasive access to the hip joint compared with standard open arthrotomy. The use of arthroscopy for diagnosing and treating disorders about the hip continues to evolve. The authors describe an arthroscopically assisted technique for the removal of a bullet lodged in the acetabulum of a patient who sustained a gunshot wound that entered the abdomen and traversed the rectum before ending up in the weight-bearing dome of the acetabulum. A number of issues led to the decision to use both arthroscopy and this specific technique. Most importantly was our desire to limit the amount of surrounding articular cartilage and local bone damage on removal. Minimizing the soft tissue dissection needed to access the bullet and keeping down our operative time also played a role in deciding to use this technique. We considered the risks of potential bullet fragmentation and migration, as well as a possible abdominal compartment syndrome before proceeding. This surgical technique afforded a very satisfactory outcome for this patient and serves as a model for others when encountering a similar injury pattern in a trauma patient. It is a procedure that can be performed safely, quickly, and with minimal complications for surgeons who have experience with arthroscopy of the hip joint.

Encapsulation of ePTFE in prevascularized collagen leads to peri-implant vascularization with reduced inflammation.

During the typical healing response to an implanted biomaterial, vascular-rich granulation tissue forms around the implant and later resolves into a relatively avascular, fibrous capsule. We have previously shown that a microvascular construct (MVC) consisting of isolated microvessel fragments suspended in a collagen I gel forms a persistent microcirculation in lieu of avascular scar when implanted. The current study evaluated the potential for microvascular constructs to maintain a vascularized tissue environment around an implanted biomaterial. An analysis of the peri-implant tissue around bare expanded polytetrafluoroethylene (ePTFE), ePTFE embedded within a microvascular construct, or ePTFE embedded within collagen alone revealed that the presence of the MVC, but not collagen alone, promoted vascular densities comparable to that of the granulation tissue formed around bare ePTFE. The vessels within the microvascular construct surrounding the ePTFE were perfusion competent, as determined by India ink perfusion casting, and extended into the interstices of the polymer. In contrast to bare ePTFE, the presence of the MVC or collagen alone significantly reduced the number of activated macrophages in association with ePTFE. Similar results were observed for ePTFE modified to increase cellularity and prevent the formation of an avascular scar. The microvascular construct may prove effective in forming vascularized tissue environments and limiting the number of activated macrophages around implanted polymers thereby leading to effective implant incorporation.