Application of a BMP2-binding heparan sulphate to promote periodontal regeneration

Abstract

Periodontitis is the most common inflammatory disease that leads to periodontal defects and tooth loss. Regeneration of alveolar bone and soft tissue in periodontal defects is highly desirable but remains challenging. A heparan sulphate variant (HS3) with enhanced affinity for bone morphogenetic protein-2 (BMP2) that, when combined with collagen or ceramic biomaterials, enhances bone tissue regeneration in the axial and cranial skeleton in several animal models was reported previously. In the current study, establishing the efficacy of a collagen/HS3 device for the regeneration of alveolar bone and the adjacent periodontal apparatus and related structures was sought. Collagen sponges loaded with phosphate-buffered saline, HS3, BMP2, or HS3 + BMP2 were implanted into surgically-created intra-bony periodontal defects in rat maxillae. At the 6 week end- point the maxillae were decalcified, and the extent of tissue regeneration determined by histomorphometrical analysis. The combination of collagen/HS3, collagen/BMP2 or collagen/HS3 + BMP2 resulted in a three to four-fold increase in bone regeneration and up to a 1.5 × improvement in functional ligament restoration compared to collagen alone. Moreover, the combination of collagen/HS3 + BMP2 improved the alveolar bone height and reduced the amount of epithelial growth in the apical direction. The implantation of a collagen/ HS3 combination device enhanced the regeneration of alveolar bone and associated periodontal tissues at amounts comparable to collagen in combination with the osteogenic factor BMP2. This study highlights the efficacy of a collagen/HS3 combination device for periodontal regeneration that warrants further development as a point-of-care treatment for periodontitis-related bone and soft tissue loss.

Control of tissue homeostasis by the extracellular matrix: Synthetic heparan sulfate as a promising therapeutic for periodontal health and bone regeneration

“…[41][42][43] Their critical role in transforming growth factorβ and bone morphogenetic protein signaling has not been as widely explored in periodontal ligament homeostasis as in bone. [44][45][46] Particularly for heparan sulfate, it has been demonstrated that the degree of sulfation of heparan sulfate can impact the strength of the electrostatic interactions between heparan sulfate proteoglycans and bone morphogenetic proteins. 47 However, the binding of bone morphogenetic proteins to heparan sulfate proteoglycans does not entirely depend on sulfated glycosaminoglycans.…”

“…Given the new tools available to generate such therapeutics, a clear safety profile and the ability to manufacture it at low cost, human translational studies should soon be underway. 45…”

“…They also bind the leucine‐rich repeat to the N ‐terminal region containing basic amino acids and known to attract other proteins such as bone morphogenetic proteins 41‐43 . Their critical role in transforming growth factor‐β and bone morphogenetic protein signaling has not been as widely explored in periodontal ligament homeostasis as in bone 44‐46 . Particularly for heparan sulfate, it has been demonstrated that the degree of sulfation of heparan sulfate can impact the strength of the electrostatic interactions between heparan sulfate proteoglycans and bone morphogenetic proteins 47 .…”

“…This is the beginning of a new era of glycobiology, where defined carbohydrate structures can predictably act as adjuncts in multiple clinical scenarios. Given the new tools available to generate such therapeutics, a clear safety profile and the ability to manufacture it at low cost, human translational studies should soon be underway 45 …”

BMP Signaling Pathway in Dentin Development and Diseases

“…Recombinant human BMP-2 (rhBMP-2) was approved for use for accelerating bone fusion in slow-healing fractures [ 394 ]. In addition, rhBMP-2 was used to treat periodontal wound healing and new bone formation in the maxilla and mandibles of animals and humans [ 395 , 396 , 397 , 398 , 399 , 400 , 401 , 402 , 403 ].…”