Hydroxyapatite‐Coated Small Intestinal Submucosa Membranes Enhanced Periodontal Tissue Regeneration through Immunomodulation and Osteogenesis via BMP‐2/Smad Signaling Pathway

Abstract

Periodontitis, a chronic infection causing periodontal tissue loss, may be effectively addressed with in situ tissue engineering. Small intestinal submucosa (SIS) offers exceptional biocompatibility and biodegradability but lacks sufficient osteoconductive and osteoinductive properties. This study develops and characterizes SIS coated with hydroxyapatite (SIS‐HA) and gelatin methacrylate hydroxyapatite (SIS‐Gel‐HA) using biomineralization and chemical crosslinking. The impact on periodontal tissue regeneration is assessed by evaluating macrophage immune response and osteogenic differentiation potential of periodontal ligament stem cells (PDLSCs) in vitro and rat periodontal defects in vivo. The jejunum segment, with the highest collagen type I content, is optimal for SIS preparation. SIS retains collagen fiber structure and bioactive factors. Calcium content is 2.21% in SIS‐HA and 2.45% in SIS‐Gel‐HA, with no significant differences in hydrophilicity, physicochemical properties, protein composition, or biocompatibility among SIS, SIS‐HA, SIS‐Gel, and SIS‐Gel‐HA. SIS has been found to upregulate M2 marker expression, both SIS‐HA and SIS‐Gel‐HA enhance the osteogenic differentiation of PDLSCs through the BMP‐2/Smad signaling pathway, and SIS‐HA demonstrates superior in vitro osteogenic activity. In vivo, SIS‐HA and SIS‐Gel‐HA yield denser, more mature bones with the highest BMP‐2 and Smad expression. SIS‐HA and SIS‐Gel‐HA demonstrate enhanced immunity‐osteogenesis coupling, representing a promising periodontal tissue regeneration approach.This article is protected by copyright. All rights reserved

Biomimetic Mineralized Hydroxyapatite–Fish-Scale Collagen/Chitosan Nanofibrous Membranes Promote Osteogenesis for Periodontal Tissue Regeneration

“…50 Furthermore, the biological interaction of residues in biomimetic mineralized HAp coatings was found to regulate the macrophage immune response and enhance the osteogenic differentiation of hPDLCs for periodontal bone regeneration, including activation of the osteogenic BMP/ Smad signaling pathway. 23 We also generated a periodontal defect rat model in vivo to evaluate the biosafety and effects of HAp-FCOL/CS membranes on periodontal tissue regeneration (Figure 6A). The biomimetic HAp-FCOL/CS membranes not only prevented connective tissue growth into bone defects but also efficiently recruited stem cells from the membrane, promoting collagen matrix regeneration and bone formation (Figure 7).…”

“…This bone-like HAp coating effectively enhances mesenchymal stem cell recruitment (Figure F), proliferation (Figure E), and calcium mineral deposition (Figure ). Furthermore, the biological interaction of residues in biomimetic mineralized HAp coatings was found to regulate the macrophage immune response and enhance the osteogenic differentiation of hPDLCs for periodontal bone regeneration, including activation of the osteogenic BMP/Smad signaling pathway …”

“…22 In the presence of an organic matrix, HAp crystals, as well as a structure similar to that found in natural bone tissue, can form in solution with high calcium (Ca 2+ ) and phosphate (PO 4 3− ) concentrations. 23 Strong interactions between proteins and minerals facilitate bone-like nano-HAp crystal deposition and accelerate bone regeneration and remodeling. 24 This biomimetic mineralization technique at high concentrations not only facilitates the sustained release of Ca 2+ via biomimetic HAp mineralization but also provides a favorable osteogenic microenvironment that promotes mesenchymal stem cell recruitment, osteogenic differentiation, and osteoimmunomodulatory regulation for bone tissue regeneration.…”

“…Biomimetic mineralization techniques that induce in situ hydroxyapatite (HAp) formation have recently attracted increasing attention owing to their excellent osteogenic properties . In the presence of an organic matrix, HAp crystals, as well as a structure similar to that found in natural bone tissue, can form in solution with high calcium (Ca 2+ ) and phosphate (PO 4 3– ) concentrations . Strong interactions between proteins and minerals facilitate bone-like nano-HAp crystal deposition and accelerate bone regeneration and remodeling .…”