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


Uzun Saylan B. C., Baysan G., Yılmaz O., Efeoglu C., Cilaker Micili 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: Elderberry, Carboxymethyl chitosan, Biocompatibility, Biomaterial, Bone regeneration, Soft tissue, Ultrasonography, Microcomputed tomography
  • Dokuz Eylül 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.