Successful Application of a Galanin-Coated Scaffold for Periodontal Regeneration

Abstract

The nervous system exerts finely tuned control over all aspects of the life of an organism, including pain, sensation, growth, and development. Recent developments in tissue regeneration research have increasingly turned to small molecule peptides to tailor and augment the biological response following tissue loss or injury. In the present study, we have introduced the small molecule peptide galanin (GAL) as a novel scaffold-coating agent for the healing and regeneration of craniofacial tissues. Using immunohistochemistry, we detected GAL and GAL receptors in healthy periodontal tissues and in the proximity of blood vessels, while exposure to our periodontal disease regimen resulted in a downregulation of GAL. In a 3-dimensional bioreactor culture, GAL coating of collagen scaffolds promoted cell proliferation and matrix synthesis. Following subcutaneous implantation, GAL-coated scaffolds were associated with mineralized bone-like tissue deposits, which reacted positively for alizarin red and von Kossa, and demonstrated increased expression and protein levels of RUNX2, OCN, OSX, and iBSP. In contrast, the GAL receptor antagonist galantide blocked the effect of GAL on Runx2 expression and inhibited mineralization in our subcutaneous implantation model. Moreover, GAL coating promoted periodontal regeneration and a rescue of the periodontal defect generated in our periodontitis model mice. Together, these data demonstrate the efficacy of the neuropeptide GAL as a coating material for tissue regeneration. They are also suggestive of a novel role for neurogenic signaling pathways in craniofacial and periodontal regeneration.

Oral hard tissue defect models for evaluating the regenerative efficacy of implant materials

“…Using immunohistochemistry, GAL and GAL receptors were detected in the vicinity of healthy periodontal tissue and blood vessels, whereas the onset of periodontal disease resulted in the downregulation of GAL. Thus, GAL coating promoted periodontal regeneration and repaired periodontal defects generated in periodontitis model mice 63 . The low cost of mice and the availability of multiple transgenic strains allow for in‐depth mechanistic studies.…”

“…This demonstrated that the PP‐pDA‐Ag‐COL scaffold exhibited enhanced pro‐osteogenic and antibacterial properties, and had much potential for treating alveolar/craniofacial bone regeneration 62 . In the study of Ma et al, 63 the small molecule galanin (GAL) was utilized as a novel scaffold coating agent for promoting the healing and regeneration of craniofacial tissues. Using immunohistochemistry, GAL and GAL receptors were detected in the vicinity of healthy periodontal tissue and blood vessels, whereas the onset of periodontal disease resulted in the downregulation of GAL.…”

“…Thus, GAL coating promoted periodontal regeneration and repaired periodontal defects generated in periodontitis model mice. 63 The low cost of mice and the availability of multiple transgenic strains allow for in-depth mechanistic studies. Nevertheless, their small size and thus the amount of harvested tissues required for analysis requires a large number of animals (Tables 1 and 2).…”

Tissue Engineered Neurovascularization Strategies for Craniofacial Tissue Regeneration

“…Local injection of SP promoted bone formation during mandibular distraction osteogenesis in rats, and BDNF delivery from collagen sponges , or using hyaluronic acid hydrogels ,− led to increased bone, PDL, and cementum formation compared to scaffold controls. Galanin-loaded collagen sponges promoted bone formation in inflammatory periodontal defects . Overexpression of NTRN prior to irradiation was protective of salivary gland innervation and function, and laminin matrices with entrapped NTRN promoted neurite outgrowth from isolated parasympathetic submandibular ganglia (PSG), reduced neuronal apoptosis, and increased the number of end buds, progenitor cells, and innervation in mouse submandibular glands exposed to irradiation .…”

Interface between Materials and Oral Biology

“…A novel pulp–dentin complex “tissue-chip” technology for high-fidelity studies of the tooth–material–microbiome interface is discussed (Rodrigues et al, 2021). Other articles inform on the regeneration of periodontal tissues (Ma et al, 2021) and bone using 3D-printed scaffolds (Chang, Lin et al, 2021). There also are several articles addressing modifications to implant surfaces for the purpose of enhancing bone–implant interactions and minimizing microbial infections at implant sites (Hasani-Sadrabadi et al, 2021; Ko et al, 2021; Rosa et al, 2021; Yang et al, 2021).…”