Haiyue Jiang

Adult mammalian wound healing typically results in fibrosis-associated repair rather than regenerative restoration, a process that can be further exacerbated by persistent inflammation, microbial infection, and aberrant mechanotransduction. Here, we present a nanozyme-crosslinked dual-network hydrogel (GPP@VP) that enables multi-stage modulation of this dysregulated repair cascade. The hydrogel integrates a dynamic γ-polyglutamic acid (γ-PGA)/ε-poly-L-lysine (ε-PLL) ionic network with CaP@TGnase-mediated covalent crosslinking, providing mechanical robustness, injectability, and wet-tissue adhesion. Functionally, GPP@VP enables stage-associated regulation across the healing process: Ca²⁺ release promotes rapid hemostasis at early stages; ε-PLL provides intrinsic bacteriostasis, while verteporfin (VP) enables on-demand photodynamic antibacterial activity under near-infrared (NIR) irradiation; and subsequent modulation of macrophage polarization and mechanotransduction pathways attenuates fibroblast activation and excessive extracellular matrix deposition. In vivo, GPP@VP demonstrated consistent efficacy across methicillin-resistant Staphylococcus aureus (MRSA)-infected burn wounds, a rabbit ear scar model, and postoperative adhesion models, with reduced inflammation, improved tissue remodeling, and a shift toward regenerative healing. Transcriptomic analysis further revealed coordinated regulation of immune and extracellular matrix (ECM)-related pathways. This work highlights a material strategy that enables coordinated modulation of the dysregulated repair cascade, providing a promising approach toward regenerative wound healing.

Tissue expanders are widely used for organ and tissue reconstruction surgery. Hydrogel tissue expanders that swell in a biofluid are promising for minimally invasive operations. Nevertheless, clinical applications of existing hydrogel tissue expanders exhibit simple geometries, rapid swelling and insufficient mechanical performances. Here we develop a negatively charged polyelectrolyte hydrogel ink for light-based printing and prolonged yet large expansive profiles for surface organ and tissue reconstruction. This 4D-printed hydrogel tissue expander can be moulded in architecturally sophisticated constructs that adapt to the environment and show favourable mechanics without the need of external triggers for expansion. The ionization degree of the polyelectrolyte hydrogels is tunable by pH value in the surrounding medium and allows a volume equilibrium-swelling up to 10-30 times. In a rabbit model, we use the tissue expander for reconstruction of human-size ears and breasts, highlighting their multifold advantages over existing clinically adopted methods and thus future translation potentials.

Mesenchymal stem cells (MSCs) possess immunomodulatory properties and are concurrently influenced by the local inflammatory microenvironment. Extracellular

Auricular cartilage reconstruction remains a formidable clinical challenge due to the complex anatomical structure and limited regenerative capacity of elastic cartilage. Recent advances in tissue engineering have highlighted the potential of biomimetic and smart material systems to recreate functional auricular cartilage. This review comprehensively outlines the latest progress in the design of bioinspired scaffolds that emulate extracellular matrix composition, mechanical properties and hierarchical structures. Furthermore, it discusses emerging stimulus-responsive materials capable of sensing and adapting to environmental cues—such as temperature, pH, enzymes, light, magnetism, ultrasound and mechanical stimuli—to achieve spatiotemporally controlled regeneration. While focusing on auricular cartilage, the review also draws on concepts and strategies from broader tissue engineering domains, such as bone, skin and nerve regeneration, to inform scaffold design and functional optimization. Particular attention is given to multifunctional systems integrating self-healing, nanotechnology and intelligent release platforms, as well as strategies for modulating hypoxic, immunological and biochemical microenvironments. By bridging structural biomimicry with adaptive responsiveness and self-regulation, these advanced material systems offer promising solutions for precise, durable and patient-specific auricular cartilage reconstruction. This review aims to provide a strategic framework and future directions for the development of next-generation scaffolds tailored to the complex regenerative demands of auricular tissue.

Ideal orthopedic biomaterials should replicate both the hierarchical structure and exceptional mechanical strength of natural bone. Traditional polymer-hydroxyapatite composites, typically limited up to 40 wt % hydroxyapatite, offer only modest mechanical improvements. Efforts to enhance strength by using stiffer polymers have largely failed, as increased polymer stiffness does not translate to improved composite mechanics. In contrast, natural bone’s load-bearing capability arises from the synergy between citrate, soft collagen, and ultrathin hydroxyapatite nanocrystals (~3 nanometers). Here, we show that elastic poly(octamethylene citrate) enables up to 60 wt % hydroxyapatite incorporation, mimicking the bone’s mineral content. Through a top-down “citrification” process and hot pressing, hydroxyapatite microparticles are partially dissolved and recrystallized into superthin (~5 nanometers) nanorods, enhancing organic-inorganic integration and replicating bone’s Ca/P ratios and architecture. The resulting composites exhibit compressive strengths exceeding 250 megapascals, unprecedented in polymer-mineral systems, offering a molecular design strategy for next-generation load-bearing orthopedic implants.

Microtia-anotia is a common congenital anomaly. In most cases, the genetic etiology remains unknown. The proper development of outer ear is closely related to cranial neural crest cells. Abnormal DNA recombination perturbing the function of long-range enhancers can lead to genomic disorder. Previously, we identified 4p16.1 duplications in microtia patients and revealed the enhancer function of an evolutionarily conserved region (ECR). Here we recruited additional patients and attempted to identify the minimal overlapping region and regulatory elements. We identified five individuals (F6-F10 probands) with 4p16.1 duplication. The duplications in F3 and F5 were refined to 192.6 kb and 96.1 kb. Precise junction breakpoints in F4 and F6-F10 were detected. The minimal overlapping region (chr4: 8,689,510–8712,827, hg19) contained conserved sequences in addition to ECR. Dual-luciferase assays detected enhancer activity in the TFAP2C binding and 1794 sequence. We present five additional cases of concha-type microtia with 4p16.1 duplication. The minimal overlapping region contains regulatory elements that function as in-cis tissue-specific modules, regulating downstream gene expression during development of cranial neural crest cell.

The construction and regeneration of tissue-engineered auricles are pacesetters in tissue engineering and have realized their first international clinical application. However, the unstable regeneration quality and insufficient mechanical strength have become significant obstacles impeding its clinical promotion. The perichondrium is indispensable for the nutritional and vascular supply of the underlying cartilage tissue, as well as for proper anatomical functioning and mechanical performance. This study presents a novel strategy for integrated construction of bioengineered perichondrium with bioprinted cartilage to enhance the regeneration quality and mechanical properties of tissue-engineered auricles. Simulating the anatomical structure of the native auricle designs a sandwich construction model containing bilateral perichondrium and intermediate cartilage, employing a photocrosslinkable acellular cartilage matrix and gelatin bionics matrix microenvironment, applying co-cultured auricular chondrocytes and adipose-derived stem cells creates functional cell populations, designing hatch patterns imitates microscopic arrangement structures, utilizing sacrificial materials forms interlaminar network traffic to enhance the tight connection between layers, and finally, assessing the regenerative quality of the constructs explores their feasibility and stability. The multi-level and multi-scale biomimetic construction strategy overcomes the technical limitation of the integrated construction of perichondrium-wrapped auricles and realizes biomimicry in morphology, structure, and biomechanics. Altogether, this study provides a technical reference for the hierarchical construction of complex tissues and promotes the clinical translation and application of engineered tissues or organs.