Regenerative Biomaterials最新文献

Osteoarthritis (OA) is a highly prevalent degenerative cartilage disease globally. The medical community has recognized it as one of the major public health problems today. Nanomaterials are considered the most promising avenue for OA treatment because they exhibit unique physicochemical properties such as high catalytic activity, bio-enzyme-like reaction kinetics, and modulation of joint immune responses. Besides, nanomaterials can exert higher targeting to improve therapeutic efficacy and reduce side effects. These unique advantages have led to the widespread development of nanomaterials for OA treatment, and they are gradually seeing their most prosperous moment. A timely and comprehensive review of OA pathogenesis-immunomodulation-therapeutic efficacy from a nanomaterials perspective would greatly broaden this research area. This review summarizes the recent advances in nanomaterials for OA treatment. Finally, the main challenges and opportunities for nanomaterials to modulate the immune system for OA treatment are discussed.

Androgenetic alopecia (AGA) is a globally prevalent condition, with limited treatment options and significant adverse effects associated with existing therapies. The primary pathogenic mechanisms of AGA involve androgen-mediated regulatory pathways, molecular alterations affecting hair regeneration, and inflammation in the perifollicular microenvironment. In this study, we first investigated the topical application of testosterone with varied doses for AGA mouse model induction, in which the High-dose group exhibited the most robust model development and provided a more comprehensive set of criteria for successful AGA model establishment. Then, curcumin-primed milk-derived extracellular vesicles (Cur-mEVs) were fabricated for the therapy of AGA with the in-house developed mouse model described above. It was demonstrated that Cur-mEVs remodeled the hair follicle microenvironment, evidenced by the activation of the Wnt/β-catenin signaling pathway, downregulation of transforming growth factor beta 1 expression and alleviation of perifollicular inflammation. These effects collectively regulated the hair follicle cycle and promoted hair regeneration. Overall, our results highlighted a promising therapeutic approach for AGA with potential translational possibilities.

Skeletal muscle is a vital organ of exercise and energy metabolism, playing a crucial role in maintaining body posture, enabling movement and supporting overall health. When skeletal muscle undergoes minor injuries, it has the inherent ability to self-repair and regain function. However, the ability of skeletal muscle self-repair is affected in severe muscle damage, resulting in significant muscle loss and functional impairments. For the severe muscle injury, tissue engineering strategies are used as the new methods to promote the repair and regeneration of skeletal muscle. Skeletal muscle tissue engineering (SMTE) aims to repair or regenerate skeletal muscle using seed cells, scaffolds, bioactive molecules or their combinations to reverse muscle loss caused by traumatic injury or congenital muscle defects. In this study, we provide an overview of the structure and contraction process of skeletal muscle, as well as its mechanisms of natural repair and regeneration. We describe the seed cells with myogenic potential and show natural, synthetic and composite biomaterials, as well as advanced technologies for manufacturing scaffolds used in SMTE. SMTE has broad prospects, but it still faces many challenges before clinical application. The continued advancement of muscle tissue engineering will yield innovative outcomes with significant clinical potential for skeletal muscle regeneration.

Injectable facial fillers such as Sculptra^® stimulate collagen regeneration to fill wrinkles; however, the collagen regeneration is not satisfactory due to the slow emergence of filling effect. In this study, we designed a regenerative dermal filler to provide both immediate and long-lasting filling effects. A hydrogel matrix composed of crosslinked hyaluronic acid (HA) and collagen was engineered to encapsulate porous poly(L-lactide) (PLLA) microspheres and tranexamic acid (TXA). The hydrogel matrix was administered via intradermal injection to achieve wrinkle filling. TXA is released to exert skin-whitening effects, while the porous PLLA microspheres and their degradation product, lactic acid, continuously stimulate collagen regeneration over an extended period. Facial volume increased immediately following hydrogel injection. Large amounts of new Type I and Type III collagen are generated. The porous structure of PLLA microspheres facilitated the 'penetrating growth' of collagen fibers, which effectively filled facial depressions and smoothed wrinkles. Overall, the HA/collagen composite hydrogel filler exhibited excellent esthetic effects.

[This corrects the article DOI: 10.1093/rb/rbac084.].

The biocompatibility, osteoconductivity and porous structure of coral make it a popular material for bone regeneration. However, coral mismatches host bone degradation rates and lacks osteoinductivity. No prior research has investigated the physicochemical properties of strontium-doped coralline hydroxyapatite (Sr-CHA), magnesium-doped (Mg-CHA) and strontium- and magnesium-co-doped (Sr-Mg-CHA), especially their osteogenic mechanisms. This study synthesized CHA doped with osteoinductive elements (Sr, Mg and Sr-Mg) via a hydrothermal reaction to preserve 26.5-33.5% of the unconverted inner core of calcium carbonate (CaCO₃). Under identical reaction circumstances, the Sr doping ratio in the Sr-CHA outperformed Mg in the Mg-CHA. In contrast, Sr and Mg mutually inhibit each other during co-doping in the Sr-Mg-CHA. The Sr-CHA nanorods on nanocluster spheres were the longest, while the Mg-CHA were the shortest, with the Sr-Mg-CHA occupying an intermediate length. The Sr-CHA, Mg-CHA and Sr-Mg-CHA exhibited 16 times the specific surface area and 14 times the pore volume of the coral and displayed better biocompatibility and expression levels of osteogenesis-related genes and proteins (e.g. ALP, Runx2, COL I, OCN and OPN) compared to coral in vitro, as well as improved osteogenesis than coral or Bio-Oss^®  in vivo. With its optional Sr²⁺ release concentration and degradation rates and large specific surface area and pore volume, the Sr-CHA performs the best. This study improved bone tissue engineering and regenerative medicine by enhancing the understanding of doped CHA and revealing new ways to overcome bone repair material problems.

One of the novel forms of programmed cell death, ferroptosis, has recently emerged as a hopeful treatment strategy for triple-negative breast cancer (TNBC). However, insufficient levels of intracellular reactive oxygen species (ROS) and high levels of ROS scavengers in the tumor microenvironment (TME), such as glutathione (GSH), hamper the efficacy of ferroptosis therapy. In this study, the introduction of manganese dioxide nanoparticles (MnO₂ NPs) generated cytotoxic hydroxyl radicals (⋅OH) in the TME. Importantly, MnO₂ NPs act as a nanosensitizer by consuming H₂O₂/GSH in the TME, generating oxygen (O₂) to relieve the oxygen deficiency of tumors, induce tumor oxidative stress and ultimately enhance SDT-induced ferroptosis. Additionally, oxygen, as an ultrasound contrast agent, enables the visualization of the TNBC treatment process. Meanwhile, GSH depletion in the TME leads to failure of the major cellular system defending against ferroptosis, which also promotes the accumulation of lipid peroxidation in tumor tissue. Specifically, robust autophagy induced by ROS enhances the intracellular iron pool by breaking down ferritin, thereby promoting ferroptosis in cancer cells, leading to the optimal antitumor effect. Consequently, a ferroptosis boosting system that simultaneously encapsulates MnO₂ NPs and chlorin e6 (Ce6) was constructed for the intervention of TNBC. Both the in vitro and in vivo results demonstrated that Ce6-MnO₂-BSA nanoparticles can generate a significant ROS storm under ultrasound irradiation, eliminating GSH and inducing an autophagic response that increases the effectiveness of ferroptosis, thus, inhibiting the growth of TNBC without obvious toxic side effects. This effective strategy can cascade-augment cancer cell ferroptosis, providing a new perspective for the clinical treatment of TNBC.

Recent advancements in dental implant technology have provided more reliable and durable solutions for patients. Soft tissue seal (STS) is crucial for achieving implant stability, maintaining tissue health and promoting integration with surrounding soft and hard tissues. However, the STS around implants is fragile and susceptible to disruption by oral pathogens, particularly in patients with periodontitis or poor oral hygiene, leading to complications such as peri-implant mucositis and peri-implantitis. To promote STS formation, it is crucial to maintain the balance between bacterial and host cells while effectively managing inflammation. Although titanium-based implants exhibit biocompatibility, they lack inherent antibacterial and anti-inflammatory properties. To address these challenges, we developed a dual-function antibacterial and anti-inflammatory coating using chlorhexidine (CHX) and epigallocatechin gallate (EGCG). CHX effectively reduces bacterial adhesion but may inhibit fibroblast proliferation, while EGCG provides antioxidant and anti-inflammatory benefits. Three types of EGCG/CHX composite coatings were developed on titanium surfaces at different pH values. These coatings exhibited enhanced bacterial resistance, reduced inflammation and ROS scavenging capabilities, with higher pH levels further improving their performance. In vivo studies also confirmed that these coatings effectively prevented bacterial adhesion, mitigated inflammation and promoted STS formation, thereby holding significant promise for enhancing the long-term success of dental implants.

Developing mechanical adaptable injectable gel with nucleus pulposus (NP) repairing capability for minimally invasive treatment of intervertebral disc degeneration (IDD) is of great importance in medical practice. In current work, inspired by the outcomes of polyvinyl alcohol and glycerol based injectable organohydrogel (GPG) in IDD control and the great potential of animal glue in tissue adhesion, a novel injectable and self-crosslinking adhesive organohydrogel GPG-AG was fabricated. The mechanical performance of the GPG-AG was systematically studied, possessing viscoelastic properties close to NP accompanied with strong adhesion to intervertebral disc to avoid dynamic loading induced leakage postinjection. In addition, the swelling behavior, water retention capability and degradation of the organohydrogel in situ was also explored. In vitro cellular test showed the as-fabricated organohydrogel was able to upgrade aggrecan expression while downregulate matrix metallopeptidase-13 (MMP-13) synthesis. Astoundingly, the organohydrogel revealed anti-inflammation potential of alleviating excessive reactive oxygen species, consequently creating a favored microenvironment for NP repairing. The corresponding in vivo study showed the outcome in intervertebral disc height index of the GPG-AG treated group after needle puncture was superior to previously reported GPG and control group. Taken together, this organohydrogel is expected to serve as a promising candidate for IDD control.

As the most feasible method to reconstruct long-distance peripheral nerve injuries, tissue-engineered nerves rely on biomaterials as a key driving factor. Chitooligosaccharides, intermediate products of chitosan degradation, have the ability to positively regulate nerve regeneration microenvironments. However, the impact of chitooligosaccharides on clearance of myelin debris during Wallerian degeneration is unrevealed. The focus is on exploring the role of chitooligosaccharides in myelin clearance, which is a crucial preparation stage for nerve regeneration. The effects of chitooligosaccharides on nerve regeneration were demonstrated through the morphological and functional evaluations. Then, the myelin lipids and proteins were analyzed using the morphological staining, and molecular and protein detection. The microstructure and ultrastructure observations of lysosomes and autophagosomes were performed. In addition, the proteomics and bioinformatics analysis of injured nerves treated with chitooligosaccharides. The interacting molecules and the regulatory network of Wipi1 were further predicted. On the basis of positive roles on peripheral nerve regeneration, it was illustrated that chitooligosaccharides accelerated the clearance of myelin. Furthermore chitooligosaccharides could regulate lysosomal and autophagic functions, and its role in promoting myelin clearance was mainly related to the enhanced autophagy of Schwann cells rather than macrophages. The big data analysis revealed that Wipi1 was notably upregulated in Schwann cells, mediating chitooligosaccharides to promote autophagy and myelin clearance. Meanwhile, as a potential therapeutic target, Wipi1 significantly accelerated myelin clearance and lipid metabolism after peripheral nerve injury. Our research deepens the comprehensive understanding of the positive regulatory role of chitosan and chitooligosaccharides; and it expands new content and ideas for designing and constructing better tissue-engineered nerves from the perspective of mutual communication and response between biomaterials and body tissues.