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Excessive tissue damage or loss has been solved by guided tissue regeneration and guided bone regeneration theories. However, the unfavorable degradation property of the resorbable collagen scaffold brings a big challenge to support soft tissue stabilization and time‐consuming osteogenesis. The combined effect for soft tissue and bone of the collagen scaffold with better degradation pattern has not been clearly proven. This study determined whether the double surfaces of crosslinked collagen scaffolds could optimize the combined soft tissue repair and osteogenesis. In this study, we applied the chemically crosslinking treatment to the commercially available collagen scaffolds. Surface characterization, mechanical property and cell proliferation in vitro were evaluated. Combined bilateral skin and bone defects were established with the smooth surface of scaffold facing the skin defect and the rough surface facing the bone defect on the calvaria of rat. Micro‐CT and histological evaluation were applied to determine the scaffold degradation pattern, soft tissue repair and osteogenesis. The crosslinked collagen scaffolds showed comparably favorable surface porosity, structure intactness, superhydrophilicity and mechanical properties. Compared to the native scaffolds, the crosslinked scaffolds could optimize the combined soft tissue repair and osteogenesis by preferably prolonged degradation time. Early pro‐angiogenesis facilitated soft tissue repair and osteogenesis by upregulated soft tissue matrix degradation and balanced pro‐osteogenesis with limited osteoclast‐mediated bone resorption. Taken together, this study offers a promising repair strategy for the combined soft tissue and bone defects. Further, the possible mechanism of controllable scaffold degradation should be conducted. [ABSTRACT FROM AUTHOR]

Bone defect diseases, particularly those induced by inflammation, pose a challenge for the design of ideal drug-loading scaffolds that could facilitate bone repair and eliminate inflammatory pathogens. Antimicrobial peptides LL37 is considered a promising alternative loading drug due to its broad-spectrum antimicrobial effect and various bio-functions, including osteogenic induction. In this study, we synthesized modified LL37 by adding a collagen-binding domain (CBD) to achieve specific binding to collagen and a slow release pattern. The modified peptide was indicated to exhibit similar biological activities as natural LL37 on rat BMSCs, including promotion of migration activity, anti-inflammatory activity and osteogenic induction in vitro. Ectopic bone formation experiments further confirmed the angiogenesis and osteoinduction activities in vivo. Collectively, the results indicate that LL37-CBD may be a potential loading drug for preventative and curative applications in the treatment of inflammation-induced bone diseases. [ABSTRACT FROM AUTHOR]

Abstract Oral diseases, such as periapical periodontitis and periodontitis, are characterized by inflammation-induced bone loss. LL-37, a human antimicrobial peptide (AMP), has multiple biological functions and the potential to promote osteogenesis. Therefore, this study aimed to investigate the regulatory effects of LL-37 within normal and inflammatory microenvironments. The roles of P2X7 receptor (P2X7R) and mitogen-activated protein kinase (MAPK) signaling pathway were also demonstrated. The results showed that LL-37 promoted bone marrow stromal cell (BMSC) proliferation, migration and osteogenic differentiation. LL-37 inhibited the expression of the inflammatory cytokines interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α) and receptor activator of nuclear factor kappa-B ligand (RANKL) at both protein and gene levels, and attenuated the lipopolysaccharide (LPS)-induced inhibition of osteogenesis. Immunofluorescence (IF) confirmed P2X7R expression in BMSCs. BBG, a P2X7R antagonist, significantly attenuated LL-37-promoted osteogenesis. The phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2) and c-Jun NH2-terminal kinase (JNK) increased after LL-37 stimulation, which did not affect p38 phosphorylation. The effects of LL-37 on osteogenesis-related gene expression were markedly attenuated by selective inhibitors of ERK1/2 and JNK. Furthermore, a mouse model of LPS-stimulated calvarial osteolysis was established, and results showed that LL-37 markedly inhibited osteoclastic bone resorption. In conclusion, we speculate that LL-37 inhibits inflammation and promotes BMSC osteogenesis via P2X7R and MAPK signaling pathway. [ABSTRACT FROM AUTHOR]