Regenerative Biomaterials最新文献

Oral and maxillofacial surgery is a specialized surgical field devoted to diagnosing and managing conditions affecting the oral cavity, jaws, face and related structures. In recent years, the integration of 3D printing technology has revolutionized this field, offering a range of innovative surgical devices such as patient-specific implants, surgical guides, splints, bone models and regenerative scaffolds. In this comprehensive review, we primarily focus on examining the utility of 3D-printed surgical devices in the context of oral and maxillofacial surgery and evaluating their efficiency. Initially, we provide an insightful overview of commonly utilized 3D-printed surgical devices, discussing their innovations and clinical applications. Recognizing the pivotal role of materials, we give consideration to suitable biomaterials and printing technology of each device, while also introducing the emerging fields of regenerative scaffolds and bioprinting. Furthermore, we delve into the transformative impact of 3D-printed surgical devices within specific subdivisions of oral and maxillofacial surgery, placing particular emphasis on their rejuvenating effects in bone reconstruction, orthognathic surgery, temporomandibular joint treatment and other applications. Additionally, we elucidate how the integration of 3D printing technology has reshaped clinical workflows and influenced treatment outcomes in oral and maxillofacial surgery, providing updates on advancements in ensuring accuracy and cost-effectiveness in 3D printing-based procedures.

Surgical repair with artificial chordae replacement has emerged as a standard treatment for mitral regurgitation. Expanded polytetrafluoroethylene (ePTFE) sutures are commonly employed as artificial chordae; however, they have certain limitations, such as potential long-term rupture and undesired material/tissue response. This study introduces a novel approach to artificial chordae design, termed the New Artificial Chordae (NAC), which incorporates a double-layered structure. The NAC comprises a multi-strand braided core composed of ultra-high molecular weight polyethylene (UHMWPE) fibers as the inner core, and an outer tube made of hydrophobic porous ePTFE. Compared to traditional ePTFE sutures, NAC exhibits increased flexibility, enhanced tensile strength, longer elongation and improved fatigue resistance. Moreover, NAC exhibits a more hydrophobic surface, which contributes to enhanced hemocompatibility. The study also includes in vivo investigations conducted on animal models to evaluate the biocompatibility and functional efficacy of the artificial chordae. These experiments demonstrate the enhanced durability and biocompatibility of the NAC, characterized by improved mechanical strength, minimal tissue response and reduced thrombus formation. These findings suggest the potential application of NAC as a prosthetic chordae replacement, offering promising prospects to address the limitations associated with current artificial chordae materials and providing novel ideas and approaches for the development of sustainable and biocompatible regenerative biomaterials.

A hybrid material possessing both componential and structural imitation of bone tissue is the preferable composites for bone defect repair. Inspired by the microarchitecture of native bone, this work synthesized in vitro a functional mineralized collagen fibril (MCF) material by utilizing the method of in situ co-precipitation, which was designed to proceed in the presence of Astragalus polysaccharide (APS), thus achieving APS load within the biomineralized collagen-Astragalus polysaccharide (MCAPS) fibrils. Transmission electron microscope (TEM), selected area electron diffraction (SAED) and scanning electronic microscopy (SEM) identified the details of the intrafibrillar mineralization of the MCAPS fibrils, almost mimicking the secondary level of bone tissue microstructure. A relatively uniform and continuous mineral layer formed on and within all collagen fibrils and the mineral phase was identified as typical weak-crystalline hydroxyapatite (HA) with a Ca/P ratio of about 1.53. The proliferation of bone marrow-derived mesenchymal stem cells (BMSC) and mouse embryo osteoblast precursor cells (MC3T3-E1) obtained a significant promotion by MCAPS. As for the osteogenic properties of MCAPS, a distinct increase in the alkaline phosphatase (ALP) activity and the number of calcium nodules (CN) in BMSC and MC3T3-E1 was detected. The up-regulation of three osteogenic-related genes of RUNX-2, BMP-2 and OCN were confirmed via reverse transcription-quantitative polymerase chain reaction (RT-qPCR) to further verify the osteogenic performance promotion of MCAPS. A period of 14 days of culture demonstrated that MCAPS-L exhibited a preferable efficacy in enhancing ALP activity and CN quantity, as well as in promoting the expression of osteogenic-related genes over MCAPS-M and MCAPS-H, indicating that a lower dose of APS within the material of MCAPS is more appropriate for its osteogenesis promotion properties.

Quadriceps muscles play a pivotal role in knee osteoarthritis (OA) progression and symptom manifestation, particularly pain. This research investigates the therapeutic effectiveness of muscle enhancement and support therapy (MEST), a recently developed device intended for intramuscular insertion of cog polydioxanone filaments, in quadriceps restoration to alleviate OA pain. Knee OA was induced in Sprague Dawley rats via monoiodoacetate injections. MEST or sham treatment was performed in OA or Naive rat quadriceps. Pain was assessed using paw withdrawal threshold and weight bearing. Quadriceps injury and recovery via MEST were evaluated using biomarkers, tissue morphology, muscle mass, contractile force and hindlimb torque. Satellite cell and macrophage activation, along with their activators, were also assessed. Data were compared at 1- and 3-weeks post-MEST treatment (M-W1 and M-W3). MEST treatment in OA rats caused muscle injury, indicated by elevated serum aspartate transferase and creatinine kinase levels, and local β-actin changes at M-W1. This injury triggered pro-inflammatory macrophage and satellite cell activation, accompanied by heightened interleukin-6 and insulin-like growth factor-1 levels. However, by M-W3, these processes gradually shifted toward inflammation resolution and muscle restoration. This was seen in anti-inflammatory macrophage phenotypes, sustained satellite cell activation and injury markers regressing to baseline. Quadriceps recovery in mass and strength from atrophy correlated with substantial OA pain reduction at M-W3. This study suggests that MEST-induced minor muscle injury triggers macrophage and satellite cell activation, leading to recovery of atrophied quadriceps and pain relief in OA rats.

Head and neck squamous cell carcinoma (HNSCC) is the sixth most common malignant tumor worldwide. Considering its special anatomical site and the progressive resistance to chemotherapy drugs, the development of more effective, minimally invasive and precise treatment methods is urgently needed. Nanomaterials, given their special properties, can be used as drug carrier systems to improve the therapeutic effect and reduce the adverse effects. The drug carrier systems with photothermal effect can promote the killing of cancer cells and help overcome drug resistance through heat stress. We selected dopamine, a simple raw material, and designed and synthesized three different configurations of nano-polydopamine (nPDA) nanomaterials, including nPDA balls, nPDA plates and porous nPDA balls. In addition to the self-polymerization and self-assembly, nPDA has high photothermal conversion efficiency and can be easily modified. Moreover, we loaded cisplatin into three different configurations of nPDA, creating nPDA-cis (the nano-drug carrier system with cisplatin), and comparatively studied the properties and antitumor effects of all the nPDA and nPDA-cis materials in vitro and nPDA-cis in vivo. We found that the photothermal effect of the nPDA-cis balls drug carrier system had synergistic effect with cisplatin, resulting in excellent antitumor effect and good clinical application prospects. The comparison of the three different configurations of drug carrier systems suggested the importance of optimizing the spatial configuration design and examining the physical and chemical properties in the future development of nano-drug carrier systems. In this study, we also noted the duality and complexity of the influences of heat stress on tumors in vitro and in vivo. The specific mechanisms and the synergy with chemotherapy and immunotherapy will be an important research direction in the future.

Peripheral nerve injury is a debilitating condition that have a profound impact on the overall quality of an individual's life. The repair of peripheral nerve defects continues to present significant challenges in the field. Iron oxide magnetic nanoparticles (IONPs) have been recognized as potent nanotools for promoting the regeneration of peripheral nerves due to their capability as biological carriers and their ability to template the hydrogel structure under an external magnetic field. This research used a fibrin nanofiber hydrogel loaded with IONPs (IONPs/fibrin) to promote the regeneration of peripheral nerves in rats. In vitro examination of PC12 cells on various concentrations of IONPs/fibrin hydrogels revealed a remarkable increase in NGF and VEGF expression at 2% IONPs concentration. The biocompatibility and degradation of 2% IONPs/fibrin hydrogel were assessed using the in vivo imaging system, demonstrating subcutaneous degradation within a week without immediate inflammation. Bridging a 10-mm sciatic nerve gap in Sprague Dawley rats with 2% IONPs/fibrin hydrogel led to satisfactory morphological recovery of myelinated nerve fibers. And motor functional recovery in the 2% IONPs/fibrin group was comparable to autografts at 6, 9 and 12 weeks postoperatively. Hence, the composite fibrin hydrogel incorporating 2% IONPs exhibits potential for peripheral nerve regeneration.

In recent years, bridging repair has emerged as an effective approach for the treatment of massive rotator cuff tears (MRCTs). The objective of this study was to develop a composite patch that combines superior mechanical strength and biocompatibility and evaluate its potential for enhancing the outcomes of bridging repair for MRCTs. The composite patch, referred to as the PET-matrix patch (PM), was fabricated by immersing a plain-woven PET patch in decellularized matrix gel and utilizing the freeze-drying technique. The results demonstrated that the PM has reliable mechanical properties, with a maximum failure load of up to 480 N. The decellularized matrix sponge (DMS), present on the surface of the PM, displayed a loose and porous structure, with an average pore size of 62.51 μm and a porosity of 95.43%. In vitro experiments showed significant elongation of tenocytes on the DMS, with cells spanning across multiple pores and extending multiple protrusions as observed on SEM images. In contrast, tenocytes on the PET patch appeared smaller in size and lacked significant elongation. Additionally, the DMS facilitated the proliferation, migration and differentiation of tenocytes. In a rabbit model of chronic MRCTs, the PM group showed superior outcomes compared to the PET group at 4, 8 and 12 weeks after bridging repair. The PM group displayed significantly higher tendon maturing score, larger collagen diameter in the regenerated tendon and improved tendon-to-bone healing scores compared to the PET group (P < 0.05). Moreover, the maximum failure load of the tendon-bone complex in the PM group was significantly higher than that in the PET group (P < 0.05). In summary, the PM possesses reliable mechanical properties and excellent cytocompatibility, which can significantly improve the outcomes of bridging repair for chronic MRCTs in rabbits. Therefore, it holds great potential for clinical applications.

Tissue engineering as an interdisciplinary field of biomedical sciences has raised many hopes in the treatment of cardiovascular diseases as well as development of in vitro three-dimensional (3D) cardiac models. This study aimed to engineer a cardiac microtissue using a natural hybrid hydrogel enriched by granulocyte colony-stimulating factor (G-CSF), a bone marrow-derived growth factor. Cardiac ECM hydrogel (Cardiogel: CG) was mixed with collagen type I (ColI) to form the hybrid hydrogel, which was tested for mechanical and biological properties. Three cell types (cardiac progenitor cells, endothelial cells and cardiac fibroblasts) were co-cultured in the G-CSF-enriched hybrid hydrogel to form a 3D microtissue. ColI markedly improved the mechanical properties of CG in the hybrid form with a ratio of 1:1. The hybrid hydrogel demonstrated acceptable biocompatibility and improved retention of encapsulated human foreskin fibroblasts. Co-culture of three cell types in G-CSF enriched hybrid hydrogel, resulted in a faster 3D structure shaping and a well-cellularized microtissue with higher angiogenesis compared to growth factor-free hybrid hydrogel (control). Immunostaining confirmed the presence of CD31⁺ tube-like structures as well as vimentin⁺ cardiac fibroblasts and cTNT⁺ human pluripotent stem cells-derived cardiomyocytes. Bioinformatics analysis of signaling pathways related to the G-CSF receptor in cardiovascular lineage cells, identified target molecules. The in silico-identified STAT3, as one of the major molecules involved in G-CSF signaling of cardiac tissue, was upregulated in G-CSF compared to control. The G-CSF-enriched hybrid hydrogel could be a promising candidate for cardiac tissue engineering, as it facilitates tissue formation and angiogenesis.

Atherosclerosis, a chronic and progressive condition characterized by the accumulation of inflammatory cells and lipids within artery walls, remains a leading cause of cardiovascular diseases globally. Despite considerable advancements in drug therapeutic strategies aimed at managing atherosclerosis, more effective treatment options for atherosclerosis are still warranted. In this pursuit, the emergence of β-cyclodextrin (β-CD) as a promising therapeutic agent offers a novel therapeutic approach to drug delivery targeting atherosclerosis. The hydrophobic cavity of β-CD facilitates its role as a carrier, enabling the encapsulation and delivery of various therapeutic compounds to affected sites within the vasculature. Notably, β-CD-based nanoassemblies possess the ability to reduce cholesterol levels, mitigate inflammation, solubilize hydrophobic drugs and deliver drugs to affected tissues, making these nanocomponents promising candidates for atherosclerosis management. This review focuses on three major classes of β-CD-based nanoassemblies, including β-CD derivatives-based, β-CD/polymer conjugates-based and polymer β-CD-based nanoassemblies, highlighting a variety of formulations and assembly methods to improve drug delivery and therapeutic efficacy. These β-CD-based nanoassemblies exhibit a variety of therapeutic mechanisms for atherosclerosis and offer systematic strategies for overcoming barriers to drug delivery. Finally, we discuss the present obstacles and potential opportunities in the development and application of β-CD-based nanoassemblies as novel therapeutics for managing atherosclerosis and addressing cardiovascular diseases.

Polyetheretherketone (PEEK) is a high-performance polymer suitable for use in biomedical coatings. The implants based on PEEK have been extensively studied in dental and orthopedic fields. However, their inherent inert surfaces and poor osteogenic properties limit their broader clinical applications. Thus, there is a pressing need to produce a multifunctional PEEK implant to address this issue. In response, we developed sulfonated PEEK (sPEEK)-Cobalt-parathyroid hormone (PTH) materials featuring multifunctional nanostructures. This involved loading cobalt (Co) ions and PTH (1-34) protein onto the PEEK implant to tackle this challenge. The findings revealed that the controlled release of Co²⁺ notably enhanced the vascular formation and the expression of angiogenic-related genes, and offered antimicrobial capabilities for sPEEK-Co-PTH materials. Additionally, the sPEEK-Co-PTH group exhibited improved cell compatibility and bone regeneration capacity in terms of cell activity, alkaline phosphatase (ALP) staining, matrix mineralization and osteogenic gene expression. It surpassed solely sulfonated and other functionalized sPEEK groups, demonstrating comparable efficacy even when compared to the titanium (Ti) group. Crucially, animal experiments also corroborated the significant enhancement of osteogenesis due to the dual loading of cobalt ions and PTH (1-34). This study demonstrated the potential of bioactive Co²⁺ and PTH (1-34) for bone replacement, optimizing the bone integration of PEEK implants in clinical applications.