Optic nerve injury induces rapid retinal neurodegeneration; however, how distinct retinal cell type responses are coordinated from the hyperacute injury phase to the early repair phase remains incompletely understood. In this study, to explore the dynamic changes in intercellular and intracellular signaling events between different cell types and elucidate their potential roles in retinal ganglion cell survival and early repair, we generated a time-resolved single-nucleus RNA sequencing atlas of adult male mouse retinas across five hyperacute-to-acute timepoints (2 hours, 8 hours, 1 day, 3 days, and 7 days) following optic nerve injury. Using computational network analysis, we reconstructed dynamic cell-to-cell communication and subsequent internal genetic responses among retinal ganglion cells, Müller glia, microglia, and endothelial cells. Distinct stage-specific intercellular communication networks were identified, including transient Itgb1-associated signaling between Müller glia and retinal ganglion cells that peaked at early timepoints, enhanced Nrxn1-Nlgn1-mediated signaling in endothelial cells during the acute phase, and sustained Sema6a-Plxna4 interactions in microglia through day 7. Functional pathway analysis linked these signaling events to focal adhesion, energy metabolism, immune regulation, and cell adhesion pathways. Multiplex immunofluorescence further validated the temporal dynamics and spatial localization of key signaling molecules, including Itgb1, Nlgn1, and Plxna4, consistent with the transcriptomic findings. Collectively, these results delineate a coordinated hyperacute-to-acute neuro-glial-vascular signaling network that supports retinal ganglion cell survival and identify potential molecular targets for therapeutic intervention following optic nerve injury.

Magnesium-based biomaterials show great potential in bone regeneration due to their inherent biocompatibility, osteogenic activity, and ability to modulate the immune microenvironment. However, their rapid degradation rate remains a critical barrier to clinical translation. To address these challenges, we developed a magnesium hydride-gelatin methacryloyl (MgH2-GelMA) composite with sustained release of hydrogen gas and magnesium ions, featuring a bone-mimetic organic-inorganic hybrid network. First, magnesium hydride microcrystals were coated with an inorganic silica layer to mitigate degradation; subsequently, the coated particles were embedded within an organic GelMA hydrogel matrix. The composite achieves controlled co-release of magnesium ions (Mg2+) and hydrogen gas (H2). The released Mg2+ directly stimulates the differentiation of bone marrow mesenchymal stem cells (BMSCs) into osteoblasts, accelerating osteogenesis. Concurrently, Mg2+ and H2 synergistically induce polarization of bone marrow-derived macrophages (BMDMs) toward an anti-inflammatory phenotype. During the active inflammatory phase, this polarization modulates the immune microenvironment and establishes a pro-regenerative local niche. This study not only elucidates a novel ion-gas synergistic mechanism but also provides innovative insights and theoretical foundations for advancing artificial bone materials from passive biomimetic replacement to active regenerative modulation.

The human retina is a fragile and sophisticated light-sensitive tissue in the central nervous system. Unhealthy retinas can cause irreversible visual deterioration and permanent vision loss. Effective therapeutic strategies are restricted to the treatment or reversal of these conditions. In recent years, nanoscience and nanotechnology have revolutionized targeted management of retinal diseases. Pharmaceuticals, theranostics, regenerative medicine, gene therapy, and retinal prostheses are indispensable for retinal interventions and have been significantly advanced by nanomedical innovations. Hence, this review presents novel insights into the use of versatile nanomaterial-based nanocomposites for frontier retinal applications, including non-invasive drug delivery, theranostic contrast agents, therapeutic nanoagents, gene therapy, stem cell-based therapy, retinal optogenetics and retinal prostheses, which have mainly been reported within the last 5 years. Furthermore, recent progress, potential challenges, and future perspectives in this field are highlighted and discussed in detail, which may shed light on future clinical translations and ultimately, benefit patients with retinal disorders.

The pathological mechanism of ocular disorders is closely related to dysregulated proliferation or death of ocular cells. Regulated cell death (RCD) is a form of cell death controlled by specific signaling pathways. Diverse types of RCD, such as apoptosis, ferroptosis, autophagy, pyroptosis, and necroptosis, are prevalent in many eye diseases, while the modulation of RCD can alter ocular cell fate and improve disease progression. The pharmacological inducers and inhibitors of RCD have been developed as an emerging approach for ocular therapy. However, the complex ocular anatomy and barriers hinder the efficient use of RCD modulating drugs. Nanomedicine has emerged as a versatile tool in ophthalmic applications for its advanced properties in penetrating ocular barriers, preventing burst effects and rapid inactivation, enabling targeted and controlled release, and facilitating co-delivery of therapeutic agents. Similarly, nanomedicine has been widely explored for its potential in modulating RCD to treat ocular disorders. This review provides a comprehensive overview of the mechanistic roles of five major forms of RCD in eye diseases, summarizes the application of ocular nanomedicine that targets the RCD pathways, and discusses the future prospects of RCD-targeted ocular nanomedicine. It is expected that the elaborately designed RCD-targeted nanomedicine for ocular therapy will play an indispensable role for the establishment of next-generation ocular theranostic nanoplatforms. STATEMENT OF SIGNIFICANCE: Regulated cell death (RCD) significantly manipulates ocular cell fate and is a key driver in the progression of several vision-threatening diseases. However, the complex ocular structures limit the effective use of RCD-regulating therapies. Nanomedicine has emerged as a promising tool to overcome the limitations of the ocular anatomy and precisely modulate RCD, offering new avenues for therapeutic intervention in ocular diseases. In this review, we summarize the mechanistic role of RCD in the pathogenesis of ocular disorders, review current ocular nanomedicines that target the RCD pathway, and discuss the future prospects of RCD-targeted ocular nanomedicine. We aim to provide insights into the potential of targeted nanomedicine in advancing the therapeutics of ocular disorders.

Traumatic optic neuropathy is a form of optic neuropathy resulting from trauma. Its pathophysiological mechanisms involve primary and secondary injury phases, leading to progressive retinal ganglion cell loss and axonal degeneration. Contributing factors such as physical trauma, oxidative stress, neuroinflammation, and glial scar formation exacerbate disease progression and retinal ganglion cell death. Multiple forms of cell death-including apoptosis, pyroptosis, necroptosis, and ferroptosis-are involved at different disease stages. Although current treatments, such as corticosteroid therapy and surgical interventions, have limited efficacy, cell-based therapies have emerged as a promising approach that simultaneously promotes neuroprotection and retinal ganglion cell regeneration. This review summarizes recent advances in cell-based therapies for traumatic optic neuropathy. In the context of cell replacement therapy, retinal ganglion cell-like cells derived from embryonic stem cells and induced pluripotent stem cells-via chemical induction or direct reprogramming-have demonstrated the ability to integrate into the host retina and survive for weeks to months, potentially improving visual function. Mesenchymal stem cells derived from various sources, including bone marrow, umbilical cord, placenta, and adipose tissue, have been shown to enhance retinal ganglion cell survival, stimulate axonal regeneration, and support partial functional recovery. Additionally, neural stem/progenitor cells derived from human embryonic stem cells offer neuroprotective effects and function as "neuronal relays," facilitating reconnection between damaged regions of the optic nerve and the visual pathway. Beyond direct cell transplantation, cell-derived products, such as extracellular vesicles and cell-extracted solutions, have demonstrated promising neuroprotective effects in traumatic optic neuropathy. Despite significant progress, several challenges remain, including limited integration of transplanted cells, suboptimal functional vision recovery, the need for precise timing and delivery methods, and an incomplete understanding of the role of the retinal microenvironment and glial cell activation in neuroprotection and neuroregeneration. Furthermore, studies with longer observation periods and deeper mechanistic insights into the therapeutic effects of cell-based therapies remain scarce. Two Phase I clinical trials have confirmed the safety and potential benefits of cell-based therapy for traumatic optic neuropathy, with reported improvements in visual acuity. However, further studies are needed to validate these findings and establish significant therapeutic outcomes. In conclusion, cell-based therapies hold great promise for treating traumatic optic neuropathy, but critical obstacles must be overcome to achieve functional optic nerve regeneration. Emerging bioengineering strategies, such as scaffold-based transplantation, may improve cell survival and axonal guidance. Successful clinical translation will require rigorous preclinical validation, standardized protocols, and the integration of advanced imaging techniques to optimize therapeutic efficacy.

Retinal degenerative diseases, primarily owing to the gradual loss of neuronal cells, could lead to blindness. Transplantation of retinal progenitor cells (RPCs), which had the unique ability to differentiate into neuronal cells, offered promising therapeutic potential for these diseases. However, a critical challenge in stem cell therapy was the efficient promotion of the directed proliferation and differentiation of progenitor cells. To overcome this limitation, we formulated a zinc silicate bioceramic (ZS) composite hydrogel. The experimental outcomes demonstrated that this novel material possessed substantial advantages and immense possibilities for mimicking the extracellular matrix environment, thereby effectively modulating stem cell proliferation and differentiation. Notably, it enhanced the differentiation of RPCs into neurons while suppressing glial cell differentiation. In particular, ZS had an exceptional capacity to induce the differentiation of RPCs into photoreceptor cells, a specialized type of neuronal cell. It was important to highlight that the ZS composite hydrogel predominantly facilitated the differentiation of RPCs through activation of the Tiam2-Rac signaling pathway. Concurrently, it stimulated proliferation via activation of the AKT and ERK signaling pathways. The Zn ions in the ZS composite hydrogel primarily promoted the proliferation of RPCs, while the synergistic effect of Zn ions and Si ions contributed to reducing inflammatory factor expression and promoting the neuronal differentiation of RPCs. In conclusion, the meticulous modulation of RPC proliferation and differentiation mediated by ZS bioceramics held promise for novel therapeutic strategies of retinal degenerative diseases and neurodegenerative disorders.

Critical-sized bone defects arising from bone-related diseases pose a clinical challenge, exceeding the body's natural healing capacity. Evidence has shown that a disordered microenvironment characterized by reactive oxygen species (ROS) overproduction, vascular damage, and osteoblast deficiency severely hinders bone repair. Therefore, the reconstruction of microenvironmental homeostasis post-injury is of utmost importance. Herein, a ROS-responsive scavenging GelMA loaded with METRNL (RRG-MRL) is developed, serving as a "bone microenvironment-modulating system" for targeted delivery of METRNL, which stimulates bone marrow mesenchymal stem cells (BMSCs) homing and angiogenic sprouting. Upon exposure to elevated levels of ROS within the defect region, ROS-cleavable NHS-TK-NHS linkers are disrupted, triggering responsive degradation and METRNL release. This treatment significantly reduced ROS levels and alleviated inflammation, along with increasing the levels of anti-apoptotic factors. Meanwhile, released METRNL induced endothelial cell angiogenesis by activating the c-Kit/PI3K/Akt pathway and increased secretion of SDF-1α (CXCL12) to promote BMSCs recruitment. Rat models of cranial bone defects treated with RRG-MRL demonstrated reduced ROS signal intensity in situ, increased endogenous BMSCs count, and enhanced neovascularization, resulting in accelerated bone regeneration. The proposed platform offers a multistage therapeutic approach facilitating rapid reconstruction of microenvironment homeostasis to promote bone regeneration, indicating significant clinical potential.

Precise tumor therapy is essential for improving treatment specificity, enhancing efficacy, and minimizing side effects. Targeting organelles is a key strategy for achieving this goal and is a frontier research area attracting a considerable amount of attention. The concept of organelle targeting has a significant effect on the structural design of the nanodrugs employed. Most notably, the intricate interactions among different organelles in a tumor cell essentially create a unified system. Unfortunately, this aspect might have been somewhat overlooked when existing organelle-targeting nanodrugs were designed. In this review, we underscore the synergistic relationship among the various organelles and advocate for a holistic view of organelle-targeting design. Through the integration of biology and material science, recent advancements in organelle targeting, escaping, and collaborating are consolidated to offer fresh perspectives for the development of antitumor nanomedicines.

Currently, blue light irradiation is frequently encountered in daily life and is widely considered a high-risk factor for retinal damage. In particular, blue light-induced dysfunction and death of the retinal pigment epithelium (RPE) may ultimately contribute to irreversible vision impairment and even blindness. However, the underlying pathogenic mechanism and pathogenically targeted protection against blue light-induced RPE degeneration remain unclear. In this study, through sophisticated biochemical evaluation and high-throughput sequencing, the predominant pathological process during blue light-induced RPE degeneration was confirmed to be HMOX1-mediated RPE ferroptosis, which may be involved in the Nrf2-SLC7A11-HMOX1 hierarchy. Upon further knockdown of HMOX1 with si-HMOX1 or the HMOX1 inhibitor zinc protoporphyrin (ZnPP), specific inhibition of HMOX1 overexpression significantly suppressed RPE ferroptosis. In mice, treatment with ZnPP effectively rescued RPE degeneration and visual function. These results highlighted that HMOX1-mediated ferroptosis might be a potential target for protection against blue light-induced damage to RPE cells.

Uveal melanoma (UM) is a highly aggressive ocular malignancy associated with a poor prognosis and significant resistance to conventional therapies, including surgical resection, chemotherapy, and radiotherapy, which are often limited by their efficacy and adverse side effects. Energy-conversion-based nanodynamic therapy, which facilitates the generation of reactive oxygen species (ROS), has emerged as a promising approach for cancer treatment. Here, the development of high-performance multifunctional thermoelectric nanocatalysts, specifically Cu5FeS3.6Se0.4 nanoparticles, optimized for the effective synergistic treatment of UM is reported. These nanoparticles exhibit remarkable photothermal, thermoelectric, and chemodynamic properties that enhance therapeutic efficacy. Under near-infrared light irradiation, Cu5FeS3.6Se0.4 nanoparticles generate localized hyperthermia, which not only induces direct tumor cell ablation but also produces thermoelectric potentials that facilitate ROS generation. Additionally, the hyperthermia induced by the photothermal effects of these nanoparticles accelerates a Fenton-like reaction, leading to the formation of highly reactive hydroxyl radicals for chemodynamic therapy. The resultant ROS induce oxidative stress within tumor cells, promoting mechanisms such as cuproptosis and pyroptosis. The integration of photothermal effects, thermoelectric potentials, and chemodynamic therapy within a single nanoplatform represents an efficient strategy for UM treatment, addressing the shortcomings of traditional therapies and offering a highly effective means of managing this aggressive cancer.

Macrophages play a pivotal role in the crosstalk between the immune and skeletal systems, while Mg-based biomaterials demonstrate immunomodulatory capabilities in this procedure. However, the mechanism of how Mg2+ promotes osteogenesis through the interplay of bone marrow-derived mesenchymal stem cells (BMSCs) and macrophages remains undescribed. Here, we demonstrated that a Mg-cross-linked alginate hydrogel exerted a dual enhancement of BMSCs osteogenic differentiation through the ligand-receptor pairing of the OSM/miR-370-3p-gp130 axis. On the one hand, Mg2+, released from the Mg-cross-linked hydrogel, stimulates bone marrow-derived macrophages to produce and secrete more OSM. On the other hand, Mg2+ lowers the miR-370-3p level in BMSCs and in turn, reverses its suppression on gp130. Then, the OSM binds to the gp130 heterodimer receptor and activates intracellular osteogenic programs in BMSCs. Taken together, this study reveals a novel cross-talk pattern between the skeletal and immune systems under Mg2+ stimulation. This study not only brings new insights into the immunomodulatory properties of Mg-based biomaterials for orthopedic applications but also enriches the miRNA regulatory network and provides a promising target to facilitate bone regeneration in large bone defects.

Repair of large bone defects is a sophisticated physiological process involving the meticulous orchestration of cell activation, proliferation, and differentiation. Cellular interactions between different cell types are paramount for successful bone regeneration, making it a challenging yet fascinating area of research and clinical practice. With increasing evidence underscoring the essential role of exosomes in facilitating intercellular and cell-microenvironment communication, they have emerged as an encouraging therapeutic strategy to promote bone repair due to their non-immunogenicity, diverse sources, and potent bioactivity. In this study, we characterized a distinctive population of Krt14+Ctsk+ cells from the orbital mucoperiosteum. In vitro experiments confirmed that exosomes from Krt14+Ctsk+ cells dramatically boosted the capacities of human umbilical vein endothelial cells (HUVECs) to proliferate, migrate, and induce angiogenesis. Additionally, the exosomes notably elevated the expression of osteogenic markers, thereby indicating their potential to augment osteogenic capabilities. Furthermore, in vivo experiments utilizing a rat calvarial defect model verified that exosome-loaded sodium alginate (SA) hydrogels accelerated local vascularized bone regeneration within the defective regions. Collectively, these findings suggest that exosomes secreted by Krt14+Ctsk+ cells offer an innovative method to accelerate bone repair via coupling enhanced osteogenesis and angiogenesis, highlighting the therapeutic potential in bone repair.

Retinal ischemia is an ophthalmic emergency often caused by cardiovascular diseases, leading to irreversible vision loss and even blindness. Innovative retinal ischemia treatments are needed due to limited options. The pathological mechanisms involve retinal cell apoptosis and microglial activation. The pituitary adenylate cyclase-activating polypeptide (PACAP) is a well distributed neuropeptide found in both central nervous system and peripheral organs. Though it shows great anti-apoptosis and anti-microglia activation properties, it is rapidly cleared by intravitreal injection. Herein, we established a novel poly(ethylene glycol) (PEG) hydrogel system by cross-linking 4arm-PEG-NHS and 4arm-PEG-NH2 to load PACAP (PACAP@Gel-PEG), which exhibited great fluidity, injectability, structural recovery ability, moderate swelling ratio and drug release ability that were appropriate for drug delivery. Then the safety and effectiveness of the PACAP@Gel-PEG were evaluated in vitro in three retinal cell lines (ARPE-19, 661 W and rRMC) and in vivo using the unilateral common carotid artery occlusion (UCCAO) mice model. The CCK-8 test and live/dead staining demonstrated that PACAP@Gel-PEG exhibited excellent biocompatibility in three retinal cell lines. Furthermore, after PACAP@Gel-PEG treatment, a great anti-apoptotic effect was observed in cells treated by CoCl2. Application of PACAP@Gel-PEG greatly improved the therapeutic efficacy of PACAP in restoring retinal function, maintaining retinal integrity, and suppressing apoptosis and microglia activation in retinal tissues. Moreover, in mice, the biosafety of PACAP@Gel-PEG was confirmed by H&E staining of systemic organs. Taken together, our results demonstrated PACAP@Gel-PEG as a promising therapeutic option for retinal ischemia, providing new strategies for vision restoration.

Osteosarcoma is the most frequent malignant primary bone tumor with a poor prognosis and remains a significant issue in clinics due to the unrepairable bone defect following surgery and the lingering tumor cells. Photodynamic therapy (PDT) with its non-invasive nature and spatiotemporally controllable feature exhibits specific therapeutic efficiency, but it is limited by phototoxicity caused by prolonged laser exposure. Herein, we design and engineer an irradiation-free bifunctional PDT scaffold (BG@SAO-RB) by integrating persistent luminescence material (SrAl2O4:Eu, Dy) and photosensitizer (rose bengal) into a 3D-printed bioactive glass scaffold for stepwise osteosarcoma elimination and bone defect repair. Owing to the design of a rechargeable internal light source, the constructed scaffolds with reactive oxygen species generation ability attain long-term and efficient PDT for osteosarcoma, leading to tumor cell killing and proliferative inhibition. The findings from tumor growth characteristics and pathological sections also confirm that BG@SAO-RB scaffolds achieve successful osteosarcoma ablation through long-term PDT in tumor-bearing nude mice. Notably, the as-designed scaffolds promote osteogenic differentiation of rat bone marrow mesenchymal stem cells and accelerate bone regeneration, which was evidenced by the improved radiological and histological manifestations. This work broadens the biomedical application of persistent luminescence materials and implicates an efficient treatment paradigm for osteosarcoma elimination and subsequent bone tissue regeneration.

Wet age-related macular degeneration (wet AMD) is a primary contributor to visual impairment and severe vision loss globally, but the prevailing treatments are often unsatisfactory. The development of conventional treatment strategies has largely been based on the understanding that the angiogenic switch of endothelial cells (ECs) is mainly dictated by angiogenic growth factors. Even though treatments targeting vascular endothelial growth factor (VEGF), like ranibizumab, are widely administered, more than half of patients still exhibit inadequate or null responses, suggesting the involvement of other pathogenic mechanisms. With advances in research in recent years, it has become well recognized that EC metabolic regulation plays an active rather than merely passive responsive role in angiogenesis. Disturbances of these metabolic pathways may lead to excessive neovascularization in angiogenic diseases such as wet AMD, therefore targeted modulation of EC metabolism represents a promising therapeutic strategy for wet AMD. In this review, we comprehensively discuss the potential applications of EC metabolic regulation in wet AMD treatment from multiple perspectives, including the involvement of ECs in wet AMD pathogenesis, the major endothelial metabolic pathways, and novel therapeutic approaches targeting metabolism for wet AMD.

Choroidal neovascularization (CNV), characterized as a prominent feature of wet age-related macular degeneration (AMD), is a primary contributor to visual impairment and severe vision loss globally, while the prevailing treatments are often unsatisfactory. The development of conventional treatment strategies has largely been based on the understanding that the angiogenic switch of endothelial cells is dictated by angiogenic growth factors alone. Even though treatments targeting vascular endothelial growth factor (VEGF), like Ranibizumab, are widely administered, more than half of the patients still exhibit inadequate or null responses, emphasizing the imperative need for solutions to this problem. Here, aiming to explore therapeutic strategies from a novel perspective of endothelial cell metabolism, a biocompatible nanomedicine delivery system is constructed by loading RGD peptide-modified liposomes with 2-deoxy-D-glucose (RGD@LP-2-DG). RGD@LP-2-DG displayed good targeting performance towards endothelial cells and excellent in vitro and in vivo inhibitory effects on neovascularization were demonstrated. Moreover, our mechanistic studies revealed that 2-DG interfered with N-glycosylation, leading to the inhibition of vascular endothelial growth factor receptor 2 (VEGFR2) and its downstream signaling. Notably, the remarkable inhibitory effect on neovascularization and biocompatibility of RGD@LP-2-DG render it a highly promising and clinically translatable therapeutic candidate for the treatment of wet AMD and other angiogenic diseases, particularly in patients who are unresponsive to currently available treatments.

Extracellular vesicles (EVs) are nanoscale membrane vesicles of various sizes that can be secreted by most cells. EVs contain a diverse array of cargo, including RNAs, lipids, proteins, and other molecules with functions of intercellular communication, immune modulation, and regulation of physiological and pathological processes. The biofluids in the eye, including tears, aqueous humor, and vitreous humor, are important sources for EV-based diagnosis of ocular disease. Because the molecular cargos may reflect the biology of their parental cells, EVs in these biofluids, as well as in the blood, have been recognized as promising candidates as biomarkers for early diagnosis of ocular disease. Moreover, EVs have also been used as therapeutics and targeted drug delivery nanocarriers in many ocular disorders because of their low immunogenicity and superior biocompatibility in nature. In this review, we provide an overview of the recent advances in the field of EV-based studies on the diagnosis and therapeutics of ocular disease. We summarized the origins of EVs applied in ocular disease, assessed different methods for EV isolation from ocular biofluid samples, highlighted bioengineering strategies of EVs as drug delivery systems, introduced the latest applications in the diagnosis and treatment of ocular disease, and presented their potential in the current clinical trials. Finally, we briefly discussed the challenges of EV-based studies in ocular disease and some issues of concern for better focusing on clinical translational studies of EVs in the future.

Phototoxicity poses a substantial challenge in photodynamic therapy, resulting in intolerable skin damage, visual impairment, and reduced quality of life. Current coping strategies, primarily focus on avoiding inappropriate photoactivation and developing targeted photosensitizers, have not effectively addressed this problem. Hence, this study aims to develop a "sunlight-friendly" photodynamic therapy strategy. Here, 1-methoxyphenazine methosulfate (MPMS) is innovatively identified as a key substance in achieving modified oxygen metabolism. MPMS demonstrates efficient catalytic shuttling under abnormal intracellular H2O2 levels, introducing a novel protective approach for oxygen metabolism and numerous life processes. By controlling MPMS administration, the switch of the photosensitizer states between "ON" (killing tumor cells) and "OFF" (safeguarding normal cells) can be achieved. This approach effectively mitigated phototoxicity and holds the potential for widespread clinical application.

The craniofacial region is composed of 23 bones, whichprovidecrucial function in keeping the normal position of brain and eyeballs,aesthetics of the craniofacial complex, facial movements, and visualfunction. Given the complex geometry and architecture, craniofacialbone defects not only affect the normal craniofacial structure butalso may result in severe craniofacial dysfunction. Therefore, theexploration of rapid, precise, and effective reconstruction of craniofacialbone defects is urgent. Recently, developments in advanced bone tissueengineering bring new hope for the ideal reconstruction of the craniofacialbone defects. This report, presenting a first-time comprehensive reviewof recent advances of biomaterials in craniofacial bone tissue engineering,overviews the modification of traditional biomaterials and developmentof advanced biomaterials applying to craniofacial reconstruction.Challenges and perspectives of biomaterial development in craniofacialfields are discussed in the end.