Despite the current biomaterials (e.g. titanium mesh and polyether ether ketone) have been applied to clinical skull repair, the limitations on mechanical match, shape adaptability, bioactivity and osteointegration have greatly limited their clinical application. In this work, we constructed a water and inflammatory microenvironment dual-responsive self-adaptive silk fibroin-magnesium oxide-based scaffold with the matrix metalloproteinase-2-responsive gelatin-methacryloyl-interleukin-4 (IL-4) coating, which presented good mechanical compliance, quickly shape matching and intraoperative reprocessability. With the capability of responding to an acute inflammation microenvironment followed by a triggered on-demand release of the IL-4, the combination of immunoactive IL-4 and Mg2+ co-ordinately facilitated metabolic reprogramming by suppressing glycolysis, promoting mitochondrial oxidative phosphorylation and modulating adenosine 5'-monophosphate-activated protein kinase (AMPK) signalling pathways in macrophages, resulting in significantly facilitating M2 macrophage activation. During the stage of tissue remodelling, the sustained release of Mg2+ further promoted macrophage M2 polarization and the expression of anti-inflammatory cytokines, significantly reduced immune response and improved ectopic osteogenesis ability. Meanwhile, the cranial defect models of male rats demonstrated that this scaffold could significantly enhance biomineralized deposition and vascularisation, and achieve good bone regeneration of cranial defects. Overall, the bioactive scaffold provides a promising biomaterial and alternative repair strategy for critical-size skull defect repair.

Tendon adhesion formation results from a fibrotic process between the tendon and surrounding tissues, typically occurring after tendon injury or surgery. This condition significantly impacts the quality of life and motor function. Currently, treating adhesions following the repair of injured tendons remains challenging and is a prominent clinical issue that needs to be addressed. This review compiles the existing pathophysiological mechanisms underlying tendon adhesion formation, with a particular focus on the critical roles of inflammation and inflammatory pathways, growth factors and their associated pathways, as well as peritendinous cellular behaviors in promoting adhesion formation. Furthermore, this paper is dedicated to summarizing the evaluation of hydrogels and electrospun fiber membranes as anti-adhesion materials, emphasizing their design, preparation, and application. Additionally, the success of composite patches created by combining these two materials in preventing tendon adhesions is reviewed, which demonstrates the broad applicability of the hydrogel and electrospun film combination. Finally, the review provides insights into future directions for preventing tendon adhesion formation, focusing on material structure and functional design.

Tendon injury is a common and challenging problem in the motor system that lacks an effective treatment, affecting daily activities and lowering the quality of life. Limited tendon regenerative capability and immune microenvironment dyshomeostasis are considered the leading causes hindering tendon repair. The chirality of biomaterials was proved to dictate immune microenvironment and dramatically affect tissue repair. Herein, chiral hierarchical structure hydroxylapatite (CHAP) nanoplates are innovatively synthesized for immunomodulatory purposes and further coated onto polylactic acid electrospinning membranes to achieve long-term release for tendon regeneration adaption. Notably, levorotatory-chiral HAP (L-CHAP) nanoplates rather than dextral-chiral or racemic-chiral exhibit good biocompatibility and bioactivity. In vitro experiments demonstrate that L-CHAP induces macrophage M2 polarization by enhancing macrophage efferocytosis, which alleviates inflammatory damage to tendon stem cells (TDSCs) through downregulated IL-17-NF-κB signaling. Meanwhile, L-CHAP-mediated macrophage efferocytosis also promotes TDSCs proliferation and tenogenic differentiation. By establishing a rat model of Achilles tendon injury, L-CHAP was demonstrated to comprehensively promoting tendon repair by enhancing macrophage efferocytosis and M2 polarization in vivo, finally leading to improvement of tendon ultrastructural and mechanical properties and motor function. This novel strategy highlights the role of L-CHAP in tendon repair and thus provides a promising therapeutic strategy for tendon injury.

Surgical treatment of colorectal diseases typically involves excising the diseased portion of the bowel and anastomosing the remaining sections to reestablish continuity. Surgical suturing has limitations in preventing anastomotic leakage and postoperative adhesion. To address these challenges, a tissue-adhesive, antibacterial, and antioxidant hydrogel is designed to cover and seal colorectal anastomotic wounds. The hydrogel is formed in situ by simply mixing oxidized hyaluronic acid, adipic acid dihydrazide-modified hyaluronic acid, ε-poly-l-lysine, and tannic acid. The hydrogel exhibits a rapid gelation rate and self-healing ability. Compared with commercial fibrin glue, the hydrogel has superior tissue-adhesive strength and wound sealing performance. The hydrogel displays potent reactive oxygen species scavenging ability and antibacterial activity against both Gram-positive and Gram-negative bacteria. The hydrogel also exhibits good biodegradation and biocompatibility. In a cecum-abdominal wall adhesion model in rats, the hydrogel attaches firmly to the injured tissues and serves as a physical barrier to prevent adhesion formation. In anastomotic leakage models after colon resection in rats and rabbits, the hydrogel effectively seals the anastomotic leakage, prevents postoperative adhesion, and promotes anastomotic healing. Thus, this multifunctional hydrogel has strong clinical potential for preventing anastomotic leakage and adhesion formation after colorectal surgery.

Materials that establish functional, stable interfaces to targeted tissues for long-term monitoring/stimulation equipped with diagnostic/therapeutic capabilities represent breakthroughs in biomedical research and clinical medicine. A fundamental challenge is the mechanical and chemical mismatch between tissues and implants that ultimately results in device failure for corrosion by biofluids and associated foreign body response. Of particular interest is in the development of bioactive materials at the level of chemistry and mechanics for high-performance, minimally invasive function, simultaneously with tissue-like compliance and in vivo biocompatibility. This review summarizes the most recent progress for these purposes, with an emphasis on material properties such as foreign body response, on integration schemes with biological tissues, and on their use as bioelectronic platforms. The article begins with an overview of emerging classes of material platforms for bio-integration with proven utility in live animal models, as high performance and stable interfaces with different form factors. Subsequent sections review various classes of flexible, soft tissue-like materials, ranging from self-healing hydrogel/elastomer to bio-adhesive composites and to bioactive materials. Additional discussions highlight examples of active bioelectronic systems that support electrophysiological mapping, stimulation, and drug delivery as treatments of related diseases, at spatiotemporal resolutions that span from the cellular level to organ-scale dimension. Envisioned applications involve advanced implants for brain, cardiac, and other organ systems, with capabilities of bioactive materials that offer stability for human subjects and live animal models. Results will inspire continuing advancements in functions and benign interfaces to biological systems, thus yielding therapy and diagnostics for human healthcare.

Critical bone defects pose a significant challenge in the realm of bone defect repair. During the repair process, bone formation is crucial, as the occurrence of invasive tissue growth into the defect, known as fibrosis, is also a possibility. Excessive fibrosis can lead to a "filling effect," wherein fibrous tissue occupies the bone defect area, thereby impeding the bone formation and repair processes. Hence, regulating the dynamic balance between fibrosis and osteogenesis is pivotal to effectively treat critical bone defects. To mitigate the rapid fibrosis rate at the bone defect site, which may result in repair failure, we have devised and fabricated a biomimetic core-shell scaffold-PCL-FAPI/GelMA/HAMA-GBA@plasmid-knockdown SHN-3 (PCL-FAPI/GH-GBA@pk SHN-3)-aimed at modulating fibrosis and vascularization processes within the new callus. The outer "shell" structure of the scaffold employs polycaprolactone (PCL) electrospun nanofibers loaded with fibroblast activating protein inhibitor (FAPI). Utilizing hydrophobic PCL electrospun fibers effectively impedes the growth of exogenous fibrous tissue, while releasing FAPI to inhibit the growth of endogenous fibroblasts. The inner layer "nucleus" structure comprises GelMA/HAMA hydrogel-supported plasmid/polyamideamine (GBA@plasmid-knockdown SHN-3), which enhances the secretion of Slit3 protein and promotes the formation of Type H blood vessels by silencing the SHN-3 gene in osteoblasts. The biomimetic "core-shell" scaffold PCL-FAPI/GH-GBA@pkSHN-3 serves to prevent excessive fibrosis of the callus and foster the formation of Type H blood vessels within the new callus, effectively averting bone nonunion and expediting the repair process of critical bone defects.

Postoperative abdominal adhesions are a common and painful complication after surgery, leading to high healthcare costs and diminished quality of life. This report presents a novel bilayer hydrogel barrier featuring an inner adhesive layer and an outer antiadhesive layer. The inner adhesive layer hydrogel (PT) is prepared by mixing polyethyleneimine (PEI) and thioctic acid (TA). The outer layer (HP) hydrogel is fabricated by the conjugation reaction of thermoresponsive zwitterionic hyaluronic acid, phenylboronic acid, and epigallocatechin gallate complex and polyvinyl alcohol based on dynamic boronic ester bond. The PEI/TA layer enhances attachment to moist tissue surfaces in vivo, and the anti-adhesive layer HP hydrogel promotes biocompatibility and anti-inflammation while minimizing protein adsorption and improving mechanical stability. The bilayer hydrogel (HPPT) exhibited rapid gelation, robust adhesion in dynamic and moist environments, superior viscoelastic properties and cellular biocompatibility. A mouse-cecum abdominal wall adhesion model is utilized to evaluate efficacy, and the HPPT hydrogel shows local retention, anti-inflammatory effect, and inhibits fibrin deposition while minimizing adhesion formation. These findings highlight the innovative structural and functional properties of the HPPT hydrogel, positioning it as a promising therapeutic barrier in peritoneal surgery aimed at reducing postoperative adhesions and enhancing surgical outcomes.

Janus hydrogels have promising applications in tendon healing and anti-peritendinous adhesions. However, their complicated preparation methods, weak mechanical properties, and unstable adhesion interfaces have severely limited their application in suture-free and high-quality tendon healing. In this work, by controlling the interfacial distribution of free -COOH groups and cationic-π structures on both sides of the hydrogels, a series of PZBA-EGCG-ALC Janus hydrogels with varying degrees of asymmetric properties are successfully prepared using a simple and efficient one-step synthesis method. The tensile strength and elongation at the break of the Janus hydrogel are as high as 0.51 ± 0.04 MPa and 922.89 ± 28.59%. In addition, the Janus hydrogel can achieve a high difference in adhesion strength (nearly 20-fold) while maintaining a strong adhesion strength on their bottom sides (up to 524.8 ± 33.1 J m-2). In the spatial dimension, its excellent mechanical compliance and one-sided adhesion behavior can provide effective mechanical support and physical barriers for the injured Achilles tendons. More importantly, the Janus hydrogel can also minimize early inflammation generation in the time dimension via its ROS-responsive PZBA-EGCG prodrug macromolecules. This study provided a more effective and convenient suture-free strategy for constructing Janus hydrogels to promote high-quality tendon healing.

Biomimetic neural substitutes, constructed through the bottom-up assembly of cell-matrix modulus via 3D bioprinting, hold great promise for neural regeneration. However, achieving precise control over the fate of neural stem cells (NSCs) to ensure biological functionality remains challenging. Cell behaviors are closely linked to cellular dynamics and cell-matrix mechanotransduction within a 3D microenvironment. To address this, a dynamic bioactive bioink is designed to provide adaptable biomechanics and instructive biochemical cues, specifically tailored for the fate commitment of NSCs, through incorporating reversible Schiff-base bonds and bioactive motifs, N-cadherin-mimicking and BDNF-mimicking peptides. We demonstrate that the dynamic properties of 3D bioprinted living fibers alleviate the mechanical confinement on NSCs and significantly enhance their mechanosensing, spreading, migration, and matrix remodeling within the 3D matrix. Additionally, the inclusion of N-cadherin-mimicking and BDNF-mimicking peptides further enhances cells' ability to sense and respond to mechanical and neurotrophic cues provided by the surrounding matrix, which accelerates the self-organization of a functional neural network within the 3D bioprinted construct, leading to significant motor and sensory function recovery in a rat complete spinal cord injury model. This work underscores the critical role of precisely designing cell-instructive bioinks for the advanced functionality of 3D bioprinted living constructs in neural regeneration.

Hydrogel microspheres are important in regenerative medicine and tissue engineering, acting as cargos of cells, drugs, growth factors, bio-inks for 3D printing, and medical devices. The antimicrobial and anti-inflammatory characteristics of hydrogel microspheres are good for treating injured tissues. However, the biological properties of hydrogel microspheres should be modified for optimal treatment of various body parts with different physiological and biochemical environments. In addition, specific preparation methods are required to produce customized hydrogel microspheres with different shapes and sizes for various clinical applications. Herein, the advances in hydrogel microspheres for biomedical applications are reviewed. Synthesis methods for hydrogel precursor solutions, manufacturing methods, and strategies for enhancing the biological functions of these hydrogel microspheres are described. The involvement of bioactive hydrogel microspheres in tissue repair is also discussed. This review anticipates fostering more insights into the design, production, and application of hydrogel microspheres in biomedicine.

Postoperative adhesions are common complications following surgery, often accompanied by pain and inflammation that significantly diminish patients' quality of life. Moreover, managing postoperative adhesions incurs substantial cost, imposing a considerable financial burden on both patients and healthcare systems. Traditional anti-adhesion materials are confronted with limitations, such as inadequate tissue adherence in a moist environment and poor degradability, underscoring the urgent need for more effective solutions. Recently, polysaccharide-based hydrogels have received considerable attention for their potential in preventing postoperative adhesions. The hydrogels not only facilitate wound healing but also effectively reduce inflammation, providing a promising approach to preventing postoperative adhesions. This review provides an extensive analysis of the progress made in the development of polysaccharide-based hydrogels for postoperative anti-adhesion therapy. It highlights their principal benefits, outlines future research trajectories, and addresses the ongoing challenges that need to be overcome.

Gout is a commonly occurring form of inflammatory arthritis caused by persistently elevated levels of uric acid. Its incidence rate rises with the increases of living standards and poor dietary habits, which has a considerable impact on the quality of life of the patients. Although there is a wide assortment of drugs available for the management of gout, the effectiveness and security of these drugs are limited by their poor chemical stability and insufficient targeting. Therefore, development of effective nanomedicine systems to overcome these problems and treat gout becomes a high priority. This review provides a detailed introduction research progress on developing advanced nanomedicines using polymers, hydrogel, nanocapsules, lipids, bionic vesicles, inorganic artificial organelles and electronically controlled conveyor systems carriers to improve gout therapy.

Microtia profoundly affects patients' appearance and psychological well-being. Tissue engineering ear cartilage scaffolds have emerged as the most promising solution for ear reconstruction. However, constructing tissue engineering ear cartilage scaffolds requires multiple passaging of chondrocytes, resulting in their dedifferentiation and loss of their special phenotypes and functions. To tackle these issues, here we employ guanidinobenzoic acid (GBA) modified generation 5 polyamidoamine (PAMAM) dendrimers (PG) as a Runx1 plasmid carrier to construct PG/pRunx1 polyplex nanoparticles. The PG/pRunx1 polyplexes are transfected into human auricular chondrocytes, significantly mitigating chondrocyte dedifferentiation and enhancing cartilage regeneration during the in vitro culture. Furthermore, we develop highly porous double-network hydrogels based on methacrylate-functionalized and oxidized chondroitin sulfate and carbohydrazide-modified gelatin and the hydrogels possessed both dynamic adaptability and mechanical support characteristics by reversible dynamic covalent crosslinking and static covalent crosslinking, serving as an ideal scaffold for tissue engineering. Consequently, chondrocytes treated with PG/pRunx1 polyplex nanoparticles are incorporated into the hydrogels to construct tissue-engineered auricular cartilage scaffolds. After subcutaneous implantation in nude mice, the scaffolds containing chondrocytes treated with PG/pRunx1 nanoparticles showed more mature cartilaginous tissue, characterized by prominent ECM deposition and enhanced chondrogenesis. Therefore, this research provides a novel strategy for the development of tissue-engineered auricular cartilage scaffolds.

The biomechanical mechanism of postoperative patellofemoral joint (PFJ) complications after open-wedge high tibial osteotomy (OWHTO) has not been investigated. This study was to determine the length changes in the patellar tendon (PT), medial patellotibial ligament (MPTL), medial patellofemoral ligament (MPFL), and quadriceps moment arm (QMA) during staircase motion before and after OWHTO. Computed tomography (CT) scans of 15 patients' lower extremities were used to reconstruct three-dimensional models, and magnetic resonance imaging (MRI) of the knee and hip joints was used to mark the soft tissue footprints. Then, such soft tissue lengths were quantified by a dual fluoroscopic imaging system (DFIS). Additionally, function scores were used to assess patient outcome changes. The results showed that there was a contraction of the PT after OWHTO due to its adhesion to the osteotomy site, causing PT length to be negatively correlated to the open-wedge angle. In addition, the shortening of the MPTL and QMA caused patellar instability and an imbalance in the strength of the lower extremities. Additionally, most knee function scores improved after OWHTO, except the Feller scores. Multiple methods should be considered to optimize surgical procedures, postoperative rehabilitation, and physical therapy.

Hyaluronic acid hydrogels are promising materials for diverse applications, yet their potential is hampered by limitations such as low self-healing efficiency and insufficient mechanical strength. Inspired by the heterogeneous structures of spider silk, we introduce a novel dual dynamically crosslinked network hydrogel. This hydrogel comprises an acylhydrazone-crosslinked network, utilizing aldehyde hyaluronic acid (AHA) and 3,3'-dithiobis (propionohydrazide) (DTP) as a first network, and a secondary network formed by hydrogen bonds-crosslinked network between tannic acid (TA) and silk fibroin (SF) with β-sheet formation. The hydrogel exhibits exceptional self-healing ability due to the dynamic and reversible nature of Schiff base bonds, disulfide bonds, and hydrogen bonds, achieving complete healing within 5 minutes. Additionally, the spider silk-inspired heterogeneous structures enhance mechanical properties. Furthermore, the incorporation of TA provides enhances adhesion, as well as remarkable antibacterial and antioxidant properties. This innovative hyaluronic acid-based hydrogel, inspired by spider silk, offers a promising avenue to fortify both the mechanical strength and self-healing capabilities of hydrogels, thus expanding opportunities for applications in tissue engineering and biomedicine.

Tendon injuries often exhibit limited healing capacity, frequently complicated by peritendinous adhesion, posing a substantial challenge in clinical tendon repair. Although present biomaterial-based membranes offer a promising strategy for tendon treatment, their clinical application is hindered by inflammation-induced adhesion. Herein, this study presents a dual-functional biomimetic tendon sheath based on a coaxial electrospun nanofibrous membrane for enhancing tendon repair and simultaneously preventing peritendinous adhesion. This nanofibrous membrane is fabricated using a coaxial electrospinning method, encapsulating celecoxib-loaded polycaprolactone (PCL) within gelatin methacryloyl (GelMA) shell. Both in vitro and in vivo analysis results demonstrated that such coaxial biomimetic tendon sheath enhanced tenogenic differentiation of tendon stem/progenitor cells (TSPCs) due to nanofibrous GelMA shell providing a suitable microenvironment surface. Simultaneously, the sustained release of celecoxib (CEL) from the core is able to significantly decrease the expression of inflammatory cytokines. Notably, in vivo assessments in animal models with patellar tendon defects revealed significant reductions in peritendinous adhesion, leading to further enhancement in tendon repair. These results underscore the potential of the coaxial nanofibrous membrane as a dual-functional biomimetic tendon sheath, offering a promising avenue for the long-term management of tendon injuries.

Adhesive hydrogels characterized by structural properties similar to the extracellular matrix, excellent biocompatibility, controlled degradation, and tunable mechanical properties have demonstrated significant potential in biomedical applications, including tissue engineering, biosensors, and drug delivery systems. These hydrogels exhibit remarkable adhesion to target substrates and can be rationally engineered to meet specific requirements. In recent decades, adhesive hydrogels have experienced significant advancements driven by the introduction of numerous multifunctional design strategies. This review initially summarizes the chemical bond-based design strategies for tissue adhesion, encompassing static covalent bonds, dynamic covalent bonds, and non-covalent interactions. Subsequently, the multiple functionalities imparted by these diverse design strategies, including highly stretchable and tough performances, responsiveness to microenvironments, anti-freezing/heating properties, conductivity, antibacterial activity, and hemostatic properties are discussed. In addition, recent advances in the biomedical applications of adhesive hydrogels, focusing on tissue repair, drug delivery, medical devices, and wearable sensors are reviewed. Finally, the current challenges are highlighted and future trends in this rapidly evolving field are discussed.

Uncontrolled hemorrhage, especially in non-compressible and deep wounds, remains a critical issue in emergency and surgical care. Existing hemostatic powders often lack rapid gelation, mechanical robustness, and adequate adherence, increasing the risk of rebleeding under high-pressure blood flow. To address these limitations, PQPP, a novel self-gelling hemostatic material composed of polyacrylamide/quaternized chitosan coacervates and polydopamine nanoparticles is developed. PQPP can rapidly absorb blood within 2 s, undergoes in situ gelation, and forms a robust adhesive hydrogel to effectively seal wounds. Its efficacy stems from the electrostatic adsorption and catechol functional groups of polydopamine nanoparticles. Importantly, PQPP exhibits high burst pressure resistance, excellent blood cell aggregation capability, outstanding biocompatibility, and antibacterial properties. Comprehensive in vitro and in vivo studies, including cytotoxicity and blood compatibility tests, as well as trials in mouse liver, heart, and vascular injury models, demonstrate PQPP's superior hemostatic performance under high-pressure conditions without causing inflammation. With its rapid gelation, robust adhesion, and mechanical integrity, PQPP represents a promising hemostatic material for immediate wound management in surgical and emergency applications.

Despite advances in tissue engineering for tendon repair, rapid functional repair is still challenging due to its specificity and is prone to complications such as postoperative infections and tendon adhesions. Smart responsive hydrogels provide new ideas for tendon therapy with their flexibly designed three-dimensional cross-linked polymer networks that respond to specific stimuli. In recent years, a variety of smart-responsive hydrogels have been developed for the treatment of tendon disorders, showing great research promise and ability to address complex challenges. This article provides a comprehensive review of recent advances in the field of smart-responsive hydrogels for the treatment of tendon disorders, with a special focus on their response properties to different physical, chemical and biological stimuli. The multiple functional properties of these innovative materials are discussed in depth, including excellent biocompatibility and biodegradability, excellent mechanical properties, biomimetic structural design, convenient injectability, and unique self-healing capabilities. These properties enable the smart-responsive hydrogels to demonstrate significant advantages in solving difficult problems in the treatment of tendon disorders, such as precise drug delivery, tendon adhesion prevention and postoperative infection control. In addition, the article looks at the future prospects of smart-responsive hydrogels and analyses the challenges they may face in achieving widespread application.

Balancing osteoblast-osteoclast (OB-OC) cross-talk is crucial for restoring bone tissue structure and function. Current clinical drugs targeting either osteogenesis or osteoclastogenesis fail to effectively regulate cross-talk, impeding efficient bone repair in osteoporosis patients. Ubiquitin-specific protease 26 (USP26) is shown to coordinate OB-OC cross-talk by independently regulating β-catenin and Iκb-α. However, effective drugs for activating USP26 are still lacking. Here, they constructed bone homeostasis repair microcarriers (BHRC) that encapsulate Usp26 mRNA-loaded lipid nanoparticles (mRNA@LNP) within MMPs-responsive GelMA hydrogel microspheres. These microcarriers target the osteoporotic microenvironment and regulate OB-OC cross-talk, thereby facilitating intervertebral fusion in osteoporotic rats. Results demonstrate that mRNA@LNP exhibits uniform particle size and high transfection efficiency, while GelMA hydrogel microspheres possess excellent biocompatibility and MMP responsiveness, providing favorable cell survival space and controllable release of mRNA@LNP. The released LNP upregulates USP26 protein expression, effectively promoting osteogenesis while suppressing osteoclast formation. In vivo experiments show that injecting BHRC into the defect site of intervertebral discs in osteoporotic rats significantly promotes tail vertebrae fusion by responding to the microenvironment and regulating cell-to-cell cross-talk. Thus, the BHRC holds great potential in regulating osteoporotic homeostasis, particularly in challenging bone defects such as intervertebral fusion in osteoporotic environments.

Understanding the transport of nanoparticles from and within hydrogels is a key issue for the design of nanocomposite hydrogels for drug delivery systems and tissue engineering. To investigate the translocation of nanocarriers from and within hydrogel networks triggered by changes of temperature, ultrasmall (8 nm) and small (80 nm) silica nanocapsules are embedded in temperature-responsive hydrogels and non-responsive hydrogels. The ultrasmall silica nanocapsules are released from temperature-responsive hydrogels to water or transported to other hydrogels upon direct activation by heating or indirect activation by Joule heating; while, they are not released from non-responsive hydrogel. Programmable transport of nanocarriers from and in hydrogels provides insights for the development of complex biomedical devices and soft robotics.

Tendons are fibroblastic structures that link muscle and bone. There are two kinds of tendon injuries, including acute and chronic. Each form of injury or deterioration can result in significant pain and loss of tendon function. The recovery of tendon damage is a complex and time-consuming recovery process. Depending on the anatomical location of the tendon tissue, the clinical outcomes are not the same. The healing of the wound process is divided into three stages that overlap: inflammation, proliferation, and tissue remodeling. Furthermore, the curing tendon has a high re-tear rate. Faced with the challenges, tendon injury management is still a clinical issue that must be resolved as soon as possible. Several newer directions and breakthroughs in tendon recovery have emerged in recent years. This article describes tendon injury and summarizes recent advances in tendon recovery, along with stem cell therapy, gene therapy, Platelet-rich plasma remedy, growth factors, drug treatment, and tissue engineering. Despite the recent fast-growing research in tendon recovery treatment, still, none of them translated to the clinical setting. This review provides a detailed overview of tendon injuries and potential preclinical approaches for treating tendon injuries.

Postoperative adhesion (POA) is a common and serious complication following various types of surgery. Current physical barriers either have a short residence time at the surgical site with a low tissue attachment capacity or are prone to undesired adhesion formation owing to the double-sided adhesive property, which limits the POA prevention efficacy of the barriers. In this study, Janus-structured microgels (Janus-MGs) with asymmetric tissue adhesion capabilities are fabricated using a novel bio-friendly gas-shearing microfluidic platform. The anti-adhesive side of Janus-MGs, which consists of alginate, hyaluronic acid, and derivatives, endows the material with separation, lubrication, and adhesion prevention properties. The adhesive side provided Janus-MGs with tissue attachment and retention capability through catechol-based adhesion, thereby enhancing the in situ adhesion prevention effect. In addition, Janus-MGs significantly reduced blood loss and shortened the hemostatic time in rats, further reducing adhesion formation. Three commonly used rat POA models with different tissue structures and motion patterns are established in this study, namely peritoneal adhesion, intrauterine adhesion, and peritendinous adhesion models, and the results showed that Janus-MGs effectively prevented the occurrence of POA in all the models. The fabrication of Janus-MGs offers a reliable strategy and a promising paradigm for preventing POA following diverse surgical procedures.

Osteoarthritis (OA), a common and disabling degenerative joint disease, affects millions of people worldwide and imposes a considerable burden on patients and society due to its high prevalence and economic costs. The pathogenesis of OA is closely related to the progressive degradation of articular cartilage and the accompany inflammation; however, articular cartilage itself cannot heal and modulate the inflammation due to the lack of nerves, blood vessels, and lymph-vessels. Therefore, reliable and effective methods to treat OA remain highly desired. Local administration of drugs or bioactive materials by intra-articular injection of the delivery system represents a promising approach to treat OA, especially considering the prolonged joint retention, cartilage or chondrocytes targeting, and stimuli-responsive release to achieve precision OA therapy. This article summarizes and discusses the advances in the currently used delivery systems (nanoparticle, hydrogel, liposome, and microsphere) and then focuses on their applications in OA treatment from the perspective of endogenous stimulus (redox reactions, pH, enzymes, and temperature) and exogenous stimulus (near-infrared, magnetic, and ultrasound)-responsive release. Finally, the challenges and potential future directions for the development of nano-delivery systems are summarized.

Hydrogels are used to provide a barrier against peritendinous adhesion formation, but when implanted intraoperatively, they degrade rapidly and aggravate early inflammatory pain. It is uncertain whether clinical efficacy can be improved by avoiding the inflammatory phase when hydrogels are delivered during adhesion formation.

(1) Compared with intraoperative hydrogel application, does ultrasound-guided postoperative application result in better total active motion (TAM) at 12 months after tendon injury? (2) Does ultrasound-guided postoperative application of hydrogels result in lower pain, better function, and better satisfaction?

This open-label, prospective, single-center, randomized controlled trial was conducted by reparative and reconstructive surgeons at the National Orthopedics Clinical Medical Center, Shanghai, People's Republic of China. Between May 2021 and December 2022, 53% (168 of 317) of patients who met our inclusion criteria were recruited, and 47% (149 of 317) of patients were excluded because of the exclusion criteria. Finally, 84 patients were randomized to the postoperative group to receive ultrasound-guided carboxymethyl chitosan (CMC) hydrogel delayed injection, and 84 patients were randomized to the intraoperative group to receive CMC hydrogel intraoperative application. Another 8% (7 of 84) of patients in the postoperative group and 10% (8 of 84) of patients in the intraoperative group were lost before the minimum study follow-up time of 1 year or had incomplete datasets, leaving 91% (153 of 168) of patients with data for analysis. Data on outcome events were analyzed according to the intention-to-treat principle, which included all patients who underwent randomization. Follow-up visits were completed at 3 weeks, 6 weeks, 3 months, 6 months, and 12 months after tendon repair. The primary outcome was TAM (ie, the sum of the degrees of active metacarpophalangeal joint, proximal interphalangeal joint, and distal interphalangeal joint flexion less the degrees from full extension; minimum clinically important difference [MCID] 20°) at 12 months. Secondary outcomes included pain (measured with a VAS; range 0 to 10, a higher score indicating worse pain; MCID 0.6), Michigan Hand Outcomes Questionnaire activities of daily living (MHQ-ADL) score (range 0 to 100, a higher score indicating better outcomes; MCID 10.1), and MHQ satisfaction (MHQ-SAT) score (range 0 to 100, a higher score indicating better outcomes; MCID 33.0).

At 12 months, the ultrasound-guided postoperative injection group had improved TAM (intraoperative 189° [95% CI 179° to 199°] versus postoperative 209° [95% CI 199° to 219°], mean difference 20° [95% CI 6° to 35°]; p = 0.006; the mean difference in the primary outcome fulfilled the MCID value at all time points). At 6 weeks, we found no clinically important difference in VAS pain scores among groups (intraoperative mean ± SD 2.0 ± 1.0 versus postoperative 1.7 ± 1.0, mean difference 0.3 [95% CI 0.1 to 0.7]; p = 0.02); however, at 3 weeks, the VAS pain scores showed clinically important difference among groups (3.6 ± 1.4 versus 2.9 ± 1.2, mean difference 0.7 [95% CI 0.3 to 1.1]; p = 0.001). At 3 months, the ultrasound-guided postoperative injection group had higher MHQ-ADL scores (intraoperative 62 ± 10 versus postoperative 75 ± 10, mean difference 13 [95% CI 11 to 17]; p < 0.001), and the mean difference of MHQ-ADL scores reached the MCID value at all time points. At 3 months, there was no clinically important difference in MHQ-SAT scores between groups (intraoperative 62 ± 8 versus postoperative 70 ± 8, mean difference 8 [95% CI 6 to 11]; p < 0.001).

Compared with intraoperative CMC hydrogel injection, postoperative ultrasound-guided injection improved the TAM and function of the affected limb, showed a short-term pain control effect, and did not increase the risk of complications. Clinical trials are needed to confirm the safety and efficacy of ultrasound-guided postoperative injection of CMC hydrogels and to determine the most effective dose and the health and economic benefits of treatment.

Level I, therapeutic study.

This study determined the development trends, analyzed collaboration networks, and identified research hotspots in the field of wearable sensors for wound care from 2007 to 2024 using a rigorous bibliometric analysis approach.

Bibliometric and scientometric analyses were performed utilizing data sourced from the Web of Science Core Collection database. This study examined publication trends, contributions from various countries and institutions, author productivity, keyword prevalence, and citation patterns to discern research hotspots and potential future avenues in the application of wearable sensors for wound care.

This study included 1177 articles, which demonstrated a marked increase in publications since 2016 and underscores the burgeoning interest in wearable sensors for wound care. China and the United States have emerged as prominent contributors to the research field, exhibiting numerous international collaborations. An analysis of keywords and citation bursts highlighted wound healing, hydrogels, and sensors as the key research foci with recent trends shifting towards the integration of wearable technology with advanced materials and artificial intelligence for advanced wound management. The research landscape is characterized by a diverse network of international collaborations and an emphasis on interdisciplinary approaches that integrate materials science, sensor technology, and clinical applications.

The utilization of wearable sensors in wound care constitutes a rapidly progressing area of research, garnering significant interest and promising avenues for future advances. The integration of wearable sensors with advanced materials and AI technologies presents a frontier of opportunity for innovating wound care methodologies, enhancing patient outcomes, and optimizing the allocation of healthcare resources.

Hydrogen (H₂) has great potential in the treatment of osteoarthritis, but its rapid diffusion and short retention time make it difficult to exert stable therapeutic effects. This study developed a short-fiber injectable material that can continuously generate hydrogen in situ to eliminate reactive oxygen species (ROS), alleviate oxidative stress and inflammation, and promote tissue repair. We prepared H-Si nanosheets with high hydrogen generation efficiency using a wet chemical exfoliation method and combined them with GelMA short fibers via electrospinning technology, achieving the in situ delivery of H-Si nanosheets and regulated hydrogen generation rate through the encapsulation and degradation of GelMA, ultimately achieving continuous and controlled hydrogen supply and stable therapeutic effects for osteoarthritis. In vitro and in vivo experiments confirmed the safety and efficacy of this material. The results showed that the material could continuously and efficiently generate hydrogen in simulated physiological environments (100 mg of material could generate 8.6 % hydrogen), effectively eliminate cellular reactive oxygen species (ROS positive rate reduced by 85.89 %), reduce cellular senescence and apoptosis (cell death rate decreased by 52 %, SA-βgal expression decreased by 78.3 %), promote normal chondrocyte function (Col II expression increased by 67.4 %, Ki67 expression increased by 87.5 %), and improve osteoarthritis in rats (OARSI score increased by 216 %). The in situ hydrogen generation and control system designed in this study provides a new method for the hydrogen's local and stable treatment of osteoarthritis. STATEMENT OF SIGNIFICANCE: Hydrogen (H₂) has great potential in the treatment of osteoarthritis by alleviating oxidative stress, but its rapid diffusion and short retention time make it difficult to exert stable therapeutic effects. This study introduces an innovative injectable material combining H-Si nanosheets and GelMA short fibers to address this issue. By enabling continuous in situ hydrogen generation, this material effectively eliminates reactive oxygen species, reduces oxidative stress and inflammation, and promotes tissue repair. In vitro and in vivo experiments demonstrate its high hydrogen generation efficiency, safety, and therapeutic efficacy, offering a promising new approach for osteoarthritis management.

Artificial skin involves multidisciplinary efforts, including materials science, biology, medicine, and tissue engineering. Recent studies have aimed at creating skins that are multifunctional, intelligent, and capable of regenerating tissue. In this work, we present a specialized 3D printing ink composed of polyurethane and bioactive glass (PU-BG) and prepare dual-function skin patch by microfluidic-regulated 3D bioprinting (MRBP) technique. The MRBP endows the skin patch with a highly controlled microstructure and superior strength. Besides, an asymmetric tri-layer is further constructed, which promotes cell attachment and growth through a dual transport mechanism based on hydrogen bonds and gradient structure from hydrophilic to superhydrophilic. More importantly, by combining the features of biomedical skin with electronic skin (e-skin), we achieved a biomedical and electronic dual-function skin patch. In vivo experiments have shown that this skin patch can enhance hemostasis, resist bacterial growth, stimulate the regeneration of blood vessels, and accelerate the healing process. Meanwhile, it also mimics the sensory functions of natural skin to realize signal detection, where the sensitivity reached up to 5.87 kPa-1, as well as cyclic stability (over 500 cycles), a wide detection range of 0-150 kPa, high pressure resolution of 0.1 % under the pressure of 100 kPa. This work offers a versatile and effective method for creating dual-function skin patches and provide new insights into wound healing and tissue repair, which have significant implications for clinical applications.

To realize effective and long-term synergistic therapy of ulcerative colitis (UC) with probiotics, we developed gastrointestinal self-adaptive and nutrient self-sufficient Akkermansia muciniphila (AKK)-gelatin porous microgels (AKK@GPMGs). In AKK@GPMGs, AKK was covered with sequential layers of proanthocyanidins (PAs), mucin (MUC), and phosphatidylcholine (PC) to obtain AKK@PAs-MUC-PC (AKK@PMP), and then encapsulated within the methacrylate-modified gelatin porous microgels. AKK@GPMGs provide sufficient mucus as a nutrition source for AKK and boost resistance to stomach acid by 30.49-fold, and colonization in the intestines is enhanced by 83.46 times. The microgels can be dissociated by matrix metalloproteinase at the inflammatory sites of the intestine, and release AKK@PMP, which acts as "band-aid" that adheres to the inflamed colon for a long time and offers improved synergistic therapy for UC. Compared to uncoated AKK, AKK@GPMGs increase reactive oxygen species scavenging capacity by 26.47 times, improve the intestinal mucus layer thickness by 5.63 times, increase the goblet cells abundance by 3.93 times, reduce intestinal permeability by 5.60 times and significantly enhance beneficial gut microbiota while repressing harmful microbiota. These results indicate that AKK@GPMGs can restore mucus layer and tight junction integrity, reduce inflammation and oxidative stress, and regulate gut microbiota homeostasis to effectively treat intestinal inflammation.

Regenerative heart valve prostheses are essential for treating valvular heart disease, which requested interactive materials that can adapt to the tissue remodeling process. Such materials typically involves intricate designs with multiple active components, limiting their translational potential. This study introduces a facile method to engineer interactive materials for heart valve regeneration using 1,1'-thiocarbonyldiimidazole (TCDI) chemistry. TCDI crosslinking forms cleavable thiourea and thiocarbamate linkages which could gradually release H2S during degradation, therefore regulates the immune microenvironment and accelerates tissue remodeling. By employing this approach, a double network hydrogel was formed on decellularized heart valves (DHVs), showcasing robust anti-calcification and anti-thrombosis properties post fatigue testing. Post-implantation, the DHVs could adaptively degrade during recellularization, releasing H2S to further support tissue regeneration. Therefore, the comprehensive endothelial cell coverage and notable extracellular matrix remodeling could be clearly observed. This accessible and integrated strategy effectively overcomes various limitations of bioprosthetic valves, showing promise as an attractive approach for immune modulation of biomaterials.

Adhesion after tendon injury, which can result in limb movement disorders, is a common clinical complication; however, effective treatment methods are lacking. Hyaluronic acid hydrogels are a new biomedical material used to prevent tendon adhesion owing to their good biocompatibility. In addition, potential drugs that inhibit adhesion formation have gradually been discovered. The anti-adhesion effects of a combination of loaded drugs into hydrogels have become an emerging trend. However, current drug delivery systems usually lack specific regulation of drug release, and the effectiveness of drugs for treating tendon adhesions is mostly flawed. In this study, we identified a new drug, imatinib mesylate (IM), that prevents tendon adhesion and explored its related molecular pathways. In addition, we designed a pH-responsive sustained-release hydrogel for delivery. Using the metal-organic framework ZIF-8 as a drug carrier, we achieved controlled drug release to increase the effective drug dose at the peak of adhesion formation to achieve better therapeutic effects. The results showed that IM blocked the formation of peritendon adhesions by inhibiting the PDGFRβ/ERK/STAT3/CLDN1 pathway. Furthermore, the hydrogel with ZIF-8 exhibited better physical properties and drug release curves than the hydrogel loaded only with drugs, showing better prevention and treatment effects on tendon adhesion.

Gelatin methacryloyl (GelMA) hydrogels is a widely used bioink because of its good biological properties and tunable physicochemical properties, which has been widely used in a variety of tissue engineering and tissue regeneration. However, pure GelMA is limited by the weak mechanical strength and the lack of continuous osteogenic induction environment, which is difficult to meet the needs of bone repair. Moreover, GelMA hydrogels are unable to respond to complex stimuli and therefore are unable to adapt to physiological and pathological microenvironments. This review focused on the functionalization strategies of GelMA hydrogel based bioinks for bone regeneration. The synthesis process of GelMA hydrogel was described in details, and various functional methods to meet the requirements of bone regeneration, including mechanical strength, porosity, vascularization, osteogenic differentiation, and immunoregulation for patient specific repair, etc. In addition, the response strategies of smart GelMA-based bioinks to external physical stimulation and internal pathological microenvironment stimulation, as well as the functionalization strategies of GelMA hydrogel to achieve both disease treatment and bone regeneration in the presence of various common diseases (such as inflammation, infection, tumor) are also briefly reviewed. Finally, we emphasized the current challenges and possible exploration directions of GelMA-based bioinks for bone regeneration.

Stable regulation of protein fate is a prerequisite for successful bone tissue repair. As a ubiquitin-specific protease (USP), USP26 can stabilize the protein fate of β-catenin to promote the osteogenic activity of mesenchymal cells (BMSCs) and significantly increased bone regeneration in bone defects in aged mice. However, direct transfection of Usp26 in vivo is inefficient. Therefore, improving the efficient expression of USP26 in target cells is the key to promoting bone tissue repair. Herein, 3D printing combined with microfluidic technology is applied to construct a functional microunit (protein fate regulating functional microunit, denoted as PFFM), which includes GelMA microspheres loaded with BMSCs overexpressing Usp26 and seeded into PCL 3D printing scaffolds. The PFFM provides a microenvironment for BMSCs, significantly promotes adhesion, and ensures cell activity and Usp26 supplementation that stabilizes β-catenin protein significantly facilitates BMSCs to express osteogenic phenotypes. In vivo experiments have shown that PFFM effectively accelerates intervertebral bone fusion. Therefore, PFFM can provide new ideas and alternatives for using USP26 for intervertebral fusion and other hard-to-repair bone defect diseases and is expected to provide clinical translational potential in future treatments.

Drug-loaded porous membranes have been deemed to be effective physicochemical barriers to separate postoperative adhesion-prone tissues in tendon healing. However, cell viability and subsequent tissue regeneration might be severely interfered with the unrestricted release and the locally excessive concentration of anti-inflammatory drugs. Herein, we report a double-layered membrane with sustained and uni-directional drug delivery features to prevent peritendinous adhesion without hampering the healing outcome. A vortex-assisted electrospinning system in combination with ibuprofen (IBU)-in-water emulsion was utilized to fabricate IBU-loaded poly-ʟ-lactic-acid (PLLA) fiber bundle membrane (PFB-IBU) as the anti-adhesion layer. The resultant highly porous structure, oleophilic and hydrophobic nature of PLLA fibers enabled in situ loading of IBU with a concentration gradient across the membrane thickness. Aligned collagen nanofibers were further deposited at the low IBU concentration side of the membrane for regulating cell growth and achieving uni-directional release of IBU. Drug release kinetics showed that the release amount of IBU from the high concentration side reached 79.32% at 14 d, while it was only 0.35% at the collagen side. Therefore, fibroblast proliferation at the high concentration side was successfully inhibited without affecting the oriented growth of tendon-derived stem cells at the other side. In vivo evaluation of the rat Achilles adhesion model confirmed the successful peritendinous anti-adhesion of our double-layered membrane, in that the macrophage recruitment, the inflammatory factor secretion and the deposition of pathological adhesion markers such as α-SMA and COL-III were all inhibited, which greatly improved the peritendinous fibrosis and restored the motor function of tendon.