4. Discussion
In recent years, several biocompatible materials belonging to different categories have been successfully used for GBR procedures, e.g. nonresorbable (ePTFE, titanium mesh), and resorbable materials (dura mater, polylactic acid, polyglycolic acid, and polyurethane). To be used in GBR procedures, each material must meet specific criteria such as biocompatibility, tissue integration, cell occlusivity, nutrient permeability, degradation kinetics, and ease of use during surgery.3[3] Nonresorbable membranes require a second surgery to be retrieved and, in case of premature exposure, there is a higher chance of bacterial colonization.
Consequently, current investigations are focused on resorbable devices, especially on type I and type III porcine or bovine collagen membranes.12[11] Collagen meets certain important requirements of a barrier for GBR procedures, including early wound stabilization, chemotactic properties to attract fibroblast, and semipermeability, but its degradation could be accelerated by polymorphonuclear leucocytes, macrophages, and periodontal bacterial pathogens resulting in early membrane collapse. The heterologous nature of collagen by-products can be related to adverse reactions, thus compromising tissue integration. Moreover, all prefabricated devices must be adapted to the individual defect, therefore compromising the handling in sites that are difficult to reach.
To overcome these drawbacks, recent experimental studies, conducted on both animal and human models, have investigated the efficacy of a newly developed synthetic hydrogel made of polyethylene glycol (PEG) to be used in bone regeneration therapy.
The purpose of this study was to analyze the role of a proprietary PEG gel formulation as a synthetic barrier, able to stimulate the angiogenic response in skin wounds, in an experimental animal model. In this study, the hydrogel was studied alone or preconditioned by adsorption of specific amelogenins or nanobioglass particles, to evaluate whether these components might modify the ability of the hydrogel to increase angiogenesis. The animal model and the surgical procedure were conducted in accordance with the previous studies proposed by Herten et al.3
To the best of our knowledge, this is the first published report of the use of Laser Doppler analysis to study perfusion of superficial skin layers following the insertion of biomaterials commonly used for oral tissue regeneration. This technique allowed creation of a perfusion map of blood flow variations at the surgical site following different times after the surgical procedure. The PEG gel formulation was shown to be a valid resorbable barrier membrane with evidence of hydrogel remnants at 16 weeks, but no evidence of inflammatory reaction or tissue necrosis.
Laser Doppler analysis highlighted statistically relevant modifications at 1 week for EMD and 2 weeks for nanobioglass. Histological analysis confirmed the angiogenetic response to both EMD and nanobioglass. EMD, whose angiogenetic potential was already reported,8[7] is able to raise a statistically significant response after 1, 2, and 8 weeks, but not after 4 weeks. One possible explanation for this pattern may be the decreasing progression of angiogenesis, which reaches a plateau at the fourth week and does not further progress until the eighth week.
In contrast, the nanobioglass reaches the highest point of vascular formation after 4 weeks, with a slower response. One possible explanation is that EMD, as an active biomolecule, is able to cause an angiogenetic burst in the early phases of wound healing, while the nanobioglass, as a scaffold, shows a slower, less intense but more steady action. The MPO assay suggests that the EMD angiogenetic stimulus is a direct action and not a consequence of an inflammatory reaction.3[3]
Angiogenesis plays a fundamental role in the wound healing process, so wherever the vascular conditions are lacking at the surgical site, consistent neoangiogenetic stimuli could enhance the healing of the wound.13–15 The results described here suggest that PEG is able to interact with the host tissue without any inflammatory reaction, regardless of the previous preconditioning of the material with other substances. In addition, we have demonstrated an increase in blood flow and angiogenesis in the area where PEG was inserted in combination with EMD, which was able to further improve PEG integration in the host tissues as well as the angiogenic response for up to 8 weeks.
Angiogenesis plays a fundamental role in the wound healing process, so wherever the vascular conditions are lacking at the surgical site, consistent neoangiogenetic stimuli could enhance the healing of the wound.[12][13][14]The results described here suggest that PEG is able to interact with the host tissue without any inflammatory reaction, regardless of the previous preconditioning of the material with other substances. In addition, we have demonstrated an increase in blood flow and angiogenesis in the area where PEG was inserted in combination with EMD, which was able to further improve PEG integration in the host tissues as well as the angiogenic response for up to 8 weeks.
This study shows how PEG, besides being a valid barrier membrane, can act as a carrier for different bioactive molecules, likely mediating their release. The substances used in our experiments, especially the EMD, appeared to improve neoangiogenesis, possibly enhancing the healing course in all places that a strong vascular support is needed, as in the GBR.
The use of biomaterials has dramatically improved tissue regeneration procedures and patient outcomes, however, several conditions may alter this process. In particular, altered blood flow supply, reduced production, and release of growth factors and their related molecules could negatively affect the healing process, as it occurs in diabetes.16[15] These results provide new insights on the regenerative efficacy of biomaterials, exploring the angiogenic and the tissue remodeling response, making these biomaterials useful for a possible immediate use in the clinical setting. If confirmed, these data could be extremely important to improve the poor outcome, due to other preexisting conditions (i.e., smoking habit or diabetes), in regenerative procedures.
Future investigations could be directed toward a combination of these three materials compounded in a single formulation, thus combining all advantages and verifying the interactions between the components.