ACS Biomaterials Science & Engineering最新文献

Adipose-derived stem cells (ADSCs) are known to promote angiogenesis and adipogenesis. However, their limited ability to efficiently target and integrate into specific tissues poses a major challenge for ADSC-based therapies. In this study, we identified a seven-amino acid peptide sequence (P7) with high specificity for ADSCs using phage display technology. P7 was then covalently conjugated to decellularized adipose-derived matrix (DAM), creating an "ADSC homing device" designed to recruit ADSCs both in vitro and in vivo. The P7-conjugated DAM significantly enhanced ADSC adhesion and proliferation in vitro. After being implanted into rat subcutaneous tissue, immunofluorescence staining after 14 days revealed that P7-conjugated DAM recruited a greater number of ADSCs, promoting angiogenesis and adipogenesis in the surrounding tissue. Moreover, CD206 immunostaining at 14 days indicated that P7-conjugated DAM facilitated the polarization of macrophages to the M2 phenotype at the implantation site. These findings demonstrate that the P7 peptide has a high affinity for ADSCs, and its conjugation with DAM significantly improves ADSC recruitment in vivo. This approach holds great potential for a wide range of applications in material surface modification.

Adding metal ions is a promising strategy to enhance the biological performance of titanium implants. In this study, we aimed to explore the effects of yttrium on the osseointegration of titanium implants. First, a series of yttrium-doped titanium surfaces were fabricated via microarc oxidation (MAO) by incorporating yttrium acetate into the electrolyte, and then the surface characteristics of different substrates were evaluated. Subsequently, the cellular behaviors of different coatings were assessed, and the osteointegration effects were examined using a rat model. Finally, high-throughput sequencing was employed to elucidate the underlying mechanisms of the yttrium-doped MAO coatings. As the results indicated, the proportion of yttrium in the coatings increased as the concentration of yttrium acetate improved. Surface characterization revealed that the yttrium-doped MAO coatings exhibited a homogeneous porous morphology, with comparable roughness and wettability to those of the undoped MAO coating, while the morphology became inconsistent when the yttrium acetate concentration reached 30 mM. The in vitro assays demonstrated that the addition of yttrium notably improved the cell adhesion, spreading, proliferation, and osteogenic differentiation of MAO coatings when doped with a low proportion, accompanied by enhanced osseointegration according to the in vivo experiments. Further exploration revealed a significant enrichment of osseointegration-related signaling factors and the activation of BMP/Smad signaling in the effects of yttrium-doped titanium coatings, which was attributed to the excessive accumulation of phosphorylated Smad1/5/9 in the nucleus. In summary, our work demonstrates that the use of MAO coatings doped with a low proportion of yttrium can enhance the osseointegration of titanium implants, providing an efficient strategy to optimize titanium implant performance.

Objective: This study aimed to investigate the effects of a sustained-release composite containing gelatin methacryloyl (Gel) and kaempferol (Ka, K) on experimental periodontitis symptoms in rats.

Methods: Forty 6-week-old male rats were randomly assigned to four treatment groups in a specific pathogen-free (SPF) environment: Control group (C), periodontitis model group (M), Gel alone group (G), and Gel_Ka composite-treated group (G_K). Treatment effects on the periodontal status of bilateral maxillary second molars in each rat group were assessed by micro-CT imaging and histology. Immunohistochemistry staining was employed to examine the effects on expression levels of inflammatory factors IL-6 and MMP9 (associated with M1 macrophages) and of the anti-inflammatory factor CD206 (associated with M2 macrophages). Additionally, treatment effects on oral and intestinal microbial communities were analyzed through 16S rDNA sequencing.

Results: Local injection treatment with the G_K composite hydrogel effectively suppressed alveolar bone resorption and reduced periodontal attachment loss and inflammation infiltration in rats with periodontitis. It reduced the expression of inflammatory factors MMP9 and IL-6 but increased the anti-inflammatory factor CD206, and it also increased the abundance of gut microbial communities producing short-chain fatty acids.

Conclusion: Local treatment with the sustained-release G_K hydrogel composite demonstrates a substantial antiperiodontitis effect in rats by locally attenuating inflammation and is associated with enhancing the microbial composition of intestinal flora, thus aiding in mitigating the inflammatory progression of experimental periodontitis.

Background: The voluntary recall and ban of several textured breast implant models worldwide, secondary to their association with Breast Implant-Associated Anaplastic Large Cell Lymphoma, has limited the key benefit of a textured surface─positional stability. We have engineered a Positionally Stable Smooth Implant (PSSI) containing millimeter-scaled cylindrical wells on the implant surface for capsule ingrowth and device stabilization. Objectives: To evaluate the long-term positional stability of PSSI designs in vivo and characterize capsule formation. Methods: Miniature breast implants were manufactured using poly(dimethylsiloxane). PSSI were designed with various dimensions of well width, depth, and number. Comparison groups consisted of smooth and textured implants. Six sterilized implants per group were implanted subcutaneously into the bilateral dorsa of Sprague-Dawley rats. Implant rotation was measured with MicroCT every 2 weeks. Implant-capsule units were explanted at 3 months for histological analysis. Results: All PSSI groups exhibited significantly less cumulative positional rotation than smooth implants (p < 0.05), with stability comparable to that of textured implants. Upon explantation, microCT and gross examination revealed notable capsule ingrowth within the PSSI wells. Histological evaluation of foreign body response showed significantly fewer pro-inflammatory M1 macrophages in the PSSI capsules compared to the textured control. Additionally, myofibroblast expression, which is implicated in capsular contracture, was significantly lower in both the PSSI and textured groups compared to smooth implants. Conclusions: This novel smooth-surface breast implant design provided equivalent positional stability and reduced pro-inflammatory M1 macrophage expression compared to textured implants. These results suggest a promising, safer alternative to textured implants for inducing positional stability.

Highly elastic and 3D-printable degradable elastomers are advantageous for many biomedical applications. Herein, we report the synthesis of a biodegradable citrate rubber poly(tetrahydrofuran-co-citrate-co-hydroxyl telechelic natural rubber) (PTCR) using citric acid, poly(tetrahydrofuran), and hydroxyl telechelic natural rubber. The citrate rubber PTCR is methacrylated to synthesize a prepolymer methacrylated-PTCR (mPTCR) that can be used to fabricate bioresorbable scaffolds via 3D printing using micro-continuous liquid interface production. Polymers were chemically characterized via NMR spectroscopy, FTIR spectroscopy, DSC, and TGA and mechanically characterized via tensile testing and crimping. The addition of rubber improved the elasticity of PTCR (658 ± 68% for dry and 415 ± 45% for swollen films) significantly compared with its nonrubber-based citrate copolymer, i.e., poly(tetrahydrofuran-co-citrate) (PTC) (550 ± 51% for dry and 88 ± 10% for swollen films). Also, the mechanical strength of PTCR reached as high as 0.8 ± 0.06 MPa after the successful addition of rubber into PTC, which had a tensile strength of 0.55 ± 0.04 MPa. Notably, the 3D-printed vascular scaffold of mPTCR demonstrated excellent mechanical competence in crimping and expansion, which is necessary for clinical use. The percent diameter recovery of mPTCR vascular scaffolds (89.4 ± 1.1%) was higher than that of its nonrubber version, i.e., methacrylated-poly(tetrahydrofuran-co-citrate) (mPTC) (77.2 ± 6.7%), illustrating the contribution of rubber in mPTCR. In vitro degradation studies showed rapid hydrolytic degradation of the PTCR elastomer in 6 weeks, whereas 3D-printed scaffolds of mPTCR degraded slowly due to its improved stability after methacrylation. The cytocompatibility and cell attachment on the vascular scaffold surfaces were successfully demonstrated by using L929 mouse myoblasts. To conclude, this study reports a citrate-based rubber that should help meet some of the scaffold mechanical requirements for tissue-engineering applications.

Infectious bone defects pose significant challenges in orthopedic practice, marked by persistent bacterial infection and ongoing inflammatory responses. Recent advancements in bone tissue engineering have led to the development of biomaterials with both antibacterial properties and the ability to promote bone regeneration, offering new solutions to these complex issues. Black phosphorus nanosheets (BPNS), a unique two-dimensional material, demonstrate exceptional biocompatibility, bioactivity, and antibacterial properties. Their combination of osteogenic, antibacterial, and anti-inflammatory effects positions BPNS as an ideal candidate for addressing bone defects complicated by infection. This Review explores the potential of BPNS-based composite biomaterials in repairing infectious bone defects, discussing their molecular mechanisms for antibacterial activity, including intrinsic antibacterial properties, photothermal therapy (PTT), photodynamic therapy (PDT), and drug delivery. The application of BPNS in treating infectious bone defects, through hydrogels, scaffolds, coatings, and fibers, is also discussed. The Review emphasizes the transformative role of BPNS in bone tissue engineering and advocates for continued research and development in this promising field.

Bone defects, whether caused by trauma, cancer, infectious diseases, or surgery, can significantly impair people's quality of life. Although autografts are the gold standard for treating bone defects, they often fall short in adequately forming bone tissue. The field of bone tissue engineering has made strides in using scaffolds with various biomaterials, stem cells, and growth factors to enhance bone healing. However, some biological structures do not yield satisfactory therapeutic outcomes for new bone formation. Recent studies have shed light on the crucial role of immunomodulation, specifically the interaction between the implanted scaffold and host immune systems, in bone regeneration. Immune cells, particularly macrophages, are pivotal in the inflammatory response, angiogenesis, and osteogenesis. This review delves into the immune system's mechanism toward foreign bodies and the recent advancements in scaffolds' physical and biological properties that foster bone regeneration by modulating macrophage polarization to an anti-inflammatory phenotype and enhancing the osteoimmune microenvironment.

Cerebral vascular disorders often accompany hypoxia-induced brain injury. In this study, we develop a zebrafish model of hypoxia-induced cerebral vascular injury to replicate the associated phenotypic changes, including cerebrovascular damage, neuronal apoptosis, and neurological dysfunction. We then explored the therapeutic potential of extracellular vesicles derived from Wharton's jelly-derived mesenchymal stem cells (WJ-MSCs) cultured on soy protein-coated surfaces. These vesicles demonstrated superior recovery efficacy, especially in restoring the blood-brain barrier integrity and improving neurological function. Our findings suggest that these potent therapeutic extracellular vesicles, easily produced from WJ-MSCs cultured in the presence of soy proteins, may mitigate hypoxia-induced brain injury by decreasing the severity of vascular disorder caused by oxidative stress. Protein-protein interactome analysis further suggests that multiple signaling pathways are likely involved in restoring normal neurovascular unit function.

Volumetric muscle loss (VML) injuries are characterized by the traumatic loss of skeletal muscle, resulting in permanent damage to both tissue architecture and electrical excitability. To address this challenge, we previously developed a three-dimensional (3D) aligned collagen-glycosaminoglycan (CG) scaffold platform that supported in vitro myotube alignment and maturation. In this work, we assessed the ability of CG scaffolds to facilitate functional muscle recovery in a rat tibialis anterior (TA) model of VML. Functional muscle recovery was assessed following implantation of either nonconductive CG or electrically conductive CG-polypyrrole (PPy) scaffolds at 4, 8, and 12 weeks postinjury by in vivo electrical stimulation of the peroneal nerve. After 12 weeks, scaffold-treated muscles produced maximum isometric torque that was significantly greater than nontreated tissues. Histological analysis further supported these reparative outcomes with evidence of regenerating muscle fibers at the material-tissue interface in scaffold-treated tissues that were not observed in nonrepaired muscles. Scaffold-treated muscles possessed higher numbers of M1 and M2 macrophages at the injury, while conductive CG-PPy scaffold-treated muscles showed significantly higher levels of neovascularization as indicated by the presence of pericytes and endothelial cells, suggesting a persistent wound repair response not observed in nontreated tissues. Finally, only tissues treated with nonconductive CG scaffolds displayed neurofilament staining similar to native muscle, further corroborating isometric contraction data. Together, these findings show that both conductive and nonconductive CG scaffolds can facilitate improved skeletal muscle function and endogenous cellular repair, highlighting their potential use as therapeutics for VML injuries.

Although the Masquelet-induced membrane technique (MIMT) is now employed worldwide for bone defects, it often needs to be repeated and autogenous bone graft. This study aims to investigate the theoretical feasibility of replacing PMMA (poly(methyl methacrylate)) bone cement with PLLA (poly-l-lactic acid)/β -TCP (beta-tricalcium phosphate)/CS (calcium sulfate) scaffold for single-stage bone defect reconstruction, which evoke the induced membrane (IM) formation in the early stage and directly acts as the implantation in the second stage to reconstruct the bone defect. We constructed a corn-like PLLA/β -TCP/CS scaffold by the fused deposition 3D printing method. The characterizations of the scaffolds were investigated systematically. The P/T15/S15 scaffolds (the PLLA/β -TCP/CS scaffold with a 15% mass fraction of β-TCP and 15% mass fraction of CS) were filled into the large-segmental radius bone defects of white rabbits to evoke the formation of IMs. HE (hematoxylin-eosin) and VG (van gieson) staining, along with immunofluorescent staining, were performed to analyze the architecture and cellularity, the expression of BMP-2 (bone morphogenetic protein-2), VEGF (vascular endothelial growth factor), and TGF-β1 (transforming growth factor-β1) was evaluated by IHC (immunohistochemistry) and WB (western-blot) respectively, the ALP (alkaline phosphatase) and ARS (alizarin red S) staining was applied to assess the osteogenic potential. The corn-like PLLA/β-TCP/CS scaffolds with excellent physicochemical properties are successfully constructed using the fused deposition 3D printing technique. The HE and VG staining, along with immunofluorescent staining, suggested that the P/T15/S15 scaffold effectively mediated the formation of IM after 6 weeks of placement. A significant presence of M2 macrophages was observed in IM. The results of IHC and WB demonstrated that the IMs derived from the P/T15/S15 scaffolds exhibited elevated levels of VEGF, BMP-2, and TGF-β1, all of which promote the osteogenic differentiation of BMSCs. The results of cellular immunofluorescence, flow cytometry, and WB indicate that P/T15/S15 regulates the phenotypic polarization of M0 macrophages toward the M2 phenotype via the PI3K/AKT/β-Catenin pathway. These findings suggest that the biodegradable PLLA/β-TCP/CS scaffold may serve as a viable alternative to PMMA bone cement for single-stage bone defect reconstruction, owing to its unique ability to stimulate IM formation and promote the polarization of macrophages toward the M2 phenotype. This work presents innovative materials and strategies for the management of bone defects.