A Biomimetic Se-nHA/PC Composite Microsphere with Synergistic Immunomodulatory and Osteogenic Ability to Activate Bone Regeneration in Periodontitis.

Accumulation of reactive oxygen species (ROS) in periodontitis exacerbates the destruction of alveolar bone. Therefore, scavenging ROS to reshape the periodontal microenvironment, alleviate the inflammatory response and promote endogenous stem cell osteogenic differentiation may be an effective strategy for treating bone resorption in periodontitis. In this study, sericin-hydroxyapatite nanoparticles (Se-nHA NPs) are synthesized using a biomimetic mineralization method. Se-nHA NPs and proanthocyanidins (PC) are then encapsulated in sericin/sodium alginate (Se/SA) using an electrostatic injection technique to prepare Se-nHA/PC microspheres. Microspheres are effective in scavenging ROS, inhibiting the polarization of macrophages toward the M1 type, and inducing the polarization of macrophages toward the M2 type. In normal or macrophage-conditioned media, the Se-nHA/PC microspheres effectively promoted the osteogenic differentiation of human periodontal ligament stem cells (hPDLSCs). Furthermore, the Se-nHA/PC microspheres demonstrated anti-inflammatory effects in a periodontitis rat model by scavenging ROS and suppressing pro-inflammatory cytokines. The Se-nHA/PC microspheres are also distinguished by their capacity to decrease alveolar bone loss, reduce osteoclast activity, and boost osteogenic factor expression. Therefore, the biomimetic Se-nHA/PC composite microspheres have efficient ROS-scavenging, anti-inflammatory, and osteogenic abilities and can be used as a multifunctional filling material for inflammatory periodontal tissue regeneration.

Multifunctional sericin-based biomineralized nanoplatforms with immunomodulatory and angio/osteo-genic activity for accelerated bone regeneration in periodontitis.

Periodontitis is a chronic inflammation caused by dental plaque. It is characterized by the accumulation of excessive reactive oxygen species (ROS) and inflammatory mediators in the periodontal area. This affects the function of host cells, activates osteoclasts, and destroys periodontal tissue. Treatments such as local debridement or antibiotic therapy for ameliorating the overactive inflammatory microenvironment and repairing periodontal tissues are challenging. This paper reports multifunctional nanoplatforms (Se-CuSrHA@EGCG) based on sericin with ROS-scavenging, immunomodulatory, angiogenic, and osteogenic capabilities. The natural protein sericin, derived from silk cocoons, is used in water/oil emulsification and cross-linking processes to create sericin nanoparticles (Se NPs). Numerous binding sites are present on the surface of Se NPs. Ion-doped hydroxyapatite nanoparticles (Se-CuSrHA NPs) can be constructed using the force between positive and negative charges. After mineralization, an antioxidant coating is formed on the surface using polyethyleneimine (PEI)/epigallocatechin gallate (EGCG). Research conducted both in vitro and in vivo demonstrates that Se-CuSrHA@EGCG NPs can efficiently scavenge ROS, regulate macrophage polarization, increase the secretion of anti-inflammatory cytokines, and balance the immune microenvironment. In addition, Se-CuSrHA@EGCG stimulates angiogenesis, inhibits osteoclasts, and accelerates periodontal tissue repair. Therefore, this is a preferable strategy to accelerate bone regeneration in patients with periodontitis.

Biomimetic fabrication of sr-silk fibroin co-assembly hydroxyapatite based microspheres with angiogenic and osteogenic properties for bone tissue engineering.

Bone defects caused by trauma, tumor resection, or developmental abnormalities are important issues in clinical practice. The vigorous development of tissue engineering technology provides new ideas and directions for regenerating bone defects. Hydroxyapatite (HAp), a bioactive ceramic, is extensively used in bone tissue engineering because of its excellent osteoinductive performance. However, its application is challenged by its single function and conventional environment-unfriendly synthesis methods. In this study, we successfully "green" synthesized sr-silk fibroin co-assembly hydroxyapatite nanoparticles (Sr-SF-HA) using silk fibroin (SF) as a biomineralized template, thus enabling it to have angiogenic activity and achieving the combination of organic and inorganic substances. Then, the rough composite microspheres loaded with Sr-SF-HA (CS/Sr-SF-HA) through electrostatic spraying technology and freeze-drying method were prepared. The CCK-8 test and live/dead cell staining showed excellent biocompatibility of CS/Sr-SF-HA. Alkaline phosphatase (ALP) staining, alizarin red staining (ARS), immunofluorescence, western blotting, and qRT-PCR test showed that CS/Sr-SF-HA activated the expression of related genes and proteins, thus inducing the osteogenic differentiation of rBMSCs. Moreover, tube formation experiments, scratch experiments, immunofluorescence, and qRT-PCR detection indicated that CS/Sr-SF-HA have good angiogenic activity. Furthermore, in vivo studies showed that the CS/Sr-SF-HA possesses excellent biocompatibility, vascular activity, as well as ectopic osteogenic ability in the subcutaneous pocket of rats. This study indicates that the construction of CS/Sr-SF-HA with angiogenic and osteogenic properties has great potential for bone tissue engineering.

Multi-functional carboxymethyl chitosan/sericin protein/halloysite composite sponge with efficient antibacterial and hemostatic properties for accelerating wound healing.

The development of wound dressings with hemostatic and antibacterial properties has attracted great attention. In this study, we prepared a multi-functional natural substance sponge (CMC/Ser-Ag/HNT) composed of carboxymethyl chitosan (CMC), sericin-silver nanoparticle (Ser-Ag), and halloysite (HNT). CMC/Ser-Ag/HNT sponge was demonstrated to bear desired hygroscopicity, porosity, compressive strength and compressive stability, cytocompatibility, and hemocompatibility. The mechanical properties (compressive strength of 100 kPa) and hemostatic capacity (hemostasis time of 15 ± 3 s in the liver injury model and 12 ± 3 s in the caudal injury model) were enhanced by introducing HNT into the CMC sponge. Ser-Ag was synthesized in situ via the redox nature of tyrosine residues in sericin in a "one-step, green" way to enhance the antibacterial activity of the hybrid sponge against Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus). In addition, the rat full-thickness skin defect model experiments demonstrated that the CMC/Ser-Ag/HNT4 sponge significantly promoted epithelialization and collagen formation. Immunofluorescence staining assays revealed that the composite sponge reduced inflammation by downregulating the expression of IL-6 and enhanced angiogenesis by upregulating VEGF expression. All the findings demonstrated the great potential of CMC/Ser-Ag/HNT sponge as versatile clinical wound dressing, especially for hemorrhagic and infected wounds.

Rational design of porous structure-based sodium alginate/chitosan sponges loaded with green synthesized hybrid antibacterial agents for infected wound healing.

An ideal wound dressing should have excellent antimicrobial properties and provide a suitable microenvironment for regenerating damaged skin tissue. In this study, we utilized sericin to biosynthesize silver nanoparticles in situ and introduced curcumin to obtain Sericin-AgNPs/Curcumin (Se-Ag/Cur) antimicrobial agent. The hybrid antimicrobial agent was then encapsulated in a physically double cross-linking 3D structure network (Sodium alginate-Chitosan, SC) to obtain the SC/Se-Ag/Cur composite sponge. The 3D structural networks were constructed through electrostatic interactions between sodium alginate and chitosan and ionic interactions between sodium alginate and calcium ions. The prepared composite sponges have excellent hygroscopicity (contact angle 51.3° ± 5.6°), moisture retention ability, porosity (67.32 % ± 3.37 %), and mechanical properties (>0.7 MPa) and exhibit good antibacterial ability against Pseudomonas aeruginosa (P. aeruginosa) and Staphylococcus aureus (S. aureus). In addition, in vivo experiments have shown that the composite sponge promotes epithelial regeneration and collagen deposition in wounds infected with S. aureus or P. aeruginosa. Tissue immunofluorescence staining analysis confirmed that the SC/Se-Ag/Cur complex sponge stimulated upregulated expression of CD31 to promote angiogenesis while downregulating TNF-α expression to reduce inflammation. These advantages make it an ideal candidate for infectious wound repair materials, providing an effective repair strategy for clinical skin trauma infections.

Biomimetic Design and Fabrication of Sericin-Hydroxyapatite Based Membranes With Osteogenic Activity for Periodontal Tissue Regeneration.

The guided tissue regeneration (GTR) technique is a promising treatment for periodontal tissue defects. GTR membranes build a mechanical barrier to control the ingrowth of the gingival epithelium and provide appropriate space for the regeneration of periodontal tissues, particularly alveolar bone. However, the existing GTR membranes only serve as barriers and lack the biological activity to induce alveolar bone regeneration. In this study, sericin-hydroxyapatite (Ser-HAP) composite nanomaterials were fabricated using a biomimetic mineralization method with sericin as an organic template. The mineralized Ser-HAP showed excellent biocompatibility and promoted the osteogenic differentiation of human periodontal membrane stem cells (hPDLSCs). Ser-HAP was combined with PVA using the freeze/thaw method to form PVA/Ser-HAP membranes. Further studies confirmed that PVA/Ser-HAP membranes do not affect the viability of hPDLSCs. Moreover, alkaline phosphatase (ALP) staining, alizarin red staining (ARS), and RT-qPCR detection revealed that PVA/Ser-HAP membranes induce the osteogenic differentiation of hPDLSCs by activating the expression of osteoblast-related genes, including ALP, Runx2, OCN, and OPN. The unique GTR membrane based on Ser-HAP induces the differentiation of hPDLSCs into osteoblasts without additional inducers, demonstrating the excellent potential for periodontal regeneration therapy.