In vivo biocompatibility of elderberry-enriched carboxymethyl chitosan in soft tissue and calvaria bone defects


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Uzun Saylan B. C., Baysan G., Yılmaz O., Efeoğlu C., Cilaker Mıçılı S., Ersoy N., ...More

BMC Oral Health, vol.25, no.1, 2025 (SCI-Expanded, Scopus) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 25 Issue: 1
  • Publication Date: 2025
  • Doi Number: 10.1186/s12903-025-06991-3
  • Journal Name: BMC Oral Health
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, CINAHL, EMBASE, MEDLINE, Directory of Open Access Journals
  • Keywords: Biocompatibility, Biomaterial, Bone regeneration, Carboxymethyl chitosan, Elderberry, Microcomputed tomography, Soft tissue, Ultrasonography
  • Open Archive Collection: AVESIS Open Access Collection
  • Ankara University Affiliated: Yes

Abstract

Background: Regeneration of soft and hard tissues remains a major challenge in periodontal and craniofacial applications, necessitating the development of multifunctional and biocompatible scaffolds. This study investigates the in vivo biocompatibility and regenerative potential of elderberry-enriched, polyethylene glycol diglycidyl ether (PEGDE)-crosslinked carboxymethyl chitosan (CMCht-E) in a rat model. Methods: Twenty-six eight-week-old female Wistar rats were randomly assigned to three experimental groups (subcutaneous, intramuscular, and calvarial; n = 7 per group). In each rat, symmetrical 5 mm defects were created, with the biomaterial implanted on one side and the contralateral side serving as the control. A sham group (n = 5) was included to account for surgical and imaging-related effects. Tissue responses were evaluated using ultrasonography, computed tomography (CT), micro-computed tomography (micro-CT), histomorphometry, and immunohistochemistry (CD68/CD163). Results: Soft tissue healing, confirmed by both ultrasonography and histological analysis, revealed similar characteristics between the biomaterial and control sites, suggesting a regenerative response closely resembling native tissue architecture. In the calvarial group, histomorphometric assessment and micro-CT analysis demonstrated a statistically significant increase in new bone formation in the CMCht-E group compared to controls (p < 0.05). There were no significant differences in CD68 and CD163 expression between biomaterial and control groups (p > 0.05). Conclusion: This first in vivo study demonstrates that CMCht-E is biocompatible and supports bone and soft tissue regeneration through controlled biodegradation. These findings highlight its promise as a naturally derived biomaterial for future use in periodontal and tissue engineering applications.