Institute of Stomatology & Department of Prosthodontics, School and Hospital of Stomatology, Wenzhou Medical University, 373 Xueyuan Xi Road, Wenzhou, Zhejiang, China.
MDRCBB, Minnesota Dental Research Center for Biomaterials and Biomechanics, University of Minnesota, Minneapolis, MN, United States.
Int J Biol Macromol. 2024 May;267(Pt 1):131480. doi: 10.1016/j.ijbiomac.2024.131480. Epub 2024 Apr 8.
Bone regeneration remains a major clinical challenge, especially when infection necessitates prolonged antibiotic treatment. This study presents a membrane composed of self-assembled and interpenetrating GL13K, an antimicrobial peptide (AMP) derived from a salivary protein, in a collagen membrane for antimicrobial activity and enhanced bone regeneration. Commercially available collagen membranes were immersed in GL13K solution, and self-assembly was initiated by raising the solution pH to synthesize the multifunctional membrane called COL-GL. COL-GL was composed of interpenetrating large collagen fibers and short GL13K nanofibrils, which increased hydrophobicity, reduced biodegradation from collagenase, and stiffened the matrix compared to control collagen membranes. Incorporation of GL13K led to antimicrobial and anti-fouling activity against early oral surface colonizer Streptococcus gordonii while not affecting fibroblast cytocompatibility or pre-osteoblast osteogenic differentiation. GL13K in solution also reduced macrophage inflammatory cytokine expression and increased pro-healing cytokine expression. Bone formation in a rat calvarial model was accelerated at eight weeks with COL-GL compared to the gold-standard collagen membrane based on microcomputed tomography and histology. Interpenetration of GL13K within collagen sidesteps challenges with antimicrobial coatings on bone regeneration scaffolds while increasing bone regeneration. This strength makes COL-GL a promising approach to reduce post-surgical infections and aid bone regeneration in dental and orthopedic applications. STATEMENT OF SIGNIFICANCE: The COL-GL membrane, incorporating the antimicrobial peptide GL13K within a collagen membrane, signifies a noteworthy breakthrough in bone regeneration strategies for dental and orthopedic applications. By integrating self-assembled GL13K nanofibers into the membrane, this study successfully addresses the challenges associated with antimicrobial coatings, exhibiting improved antimicrobial and anti-fouling activity while preserving compatibility with fibroblasts and pre-osteoblasts. The accelerated bone formation observed in a rat calvarial model emphasizes the potential of this innovative approach to minimize post-surgical infections and enhance bone regeneration outcomes. As a promising alternative for future therapeutic interventions, this material tackles the clinical challenges of extended antibiotic treatments and antibiotic resistance in bone regeneration scenarios.
骨再生仍然是一个主要的临床挑战，特别是在感染需要长期使用抗生素治疗的情况下。本研究提出了一种由自组装和互穿 GL13K 组成的膜，GL13K 是一种源自唾液蛋白的抗菌肽 (AMP)，用于抗菌活性和增强骨再生。将市售的胶原膜浸入 GL13K 溶液中，通过提高溶液 pH 值引发自组装，合成一种称为 COL-GL 的多功能膜。COL-GL 由互穿的大胶原纤维和短 GL13K 纳米原纤维组成，与对照胶原膜相比，增加了疏水性，减少了胶原酶的降解，并使基质变硬。GL13K 的掺入导致对早期口腔表面定植菌链球菌的抗菌和防污活性，同时不影响成纤维细胞的细胞相容性或前成骨细胞的成骨分化。溶液中的 GL13K 还降低了巨噬细胞炎症细胞因子的表达，增加了促愈合细胞因子的表达。与基于金标准胶原膜的微计算机断层扫描和组织学相比，在大鼠颅盖模型中，COL-GL 在八周时加速了骨形成。GL13K 在胶原中的互穿避免了骨再生支架上抗菌涂层的挑战，同时增加了骨再生。这种强度使 COL-GL 成为一种很有前途的方法，可以减少手术后感染并帮助牙科和骨科应用中的骨再生。 意义声明：COL-GL 膜将抗菌肽 GL13K 纳入胶原膜中，这是牙科和骨科应用中骨再生策略的一个重大突破。通过将自组装的 GL13K 纳米纤维整合到膜中，本研究成功解决了与抗菌涂层相关的挑战，表现出改善的抗菌和防污活性，同时保持与成纤维细胞和前成骨细胞的相容性。在大鼠颅盖模型中观察到的加速骨形成强调了这种创新方法的潜力，可以最大限度地减少手术后感染并增强骨再生效果。作为未来治疗干预的有前途的替代方案，这种材料解决了骨再生场景中抗生素治疗时间延长和抗生素耐药性的临床挑战。
