Publications

Chronic wounds affect millions worldwide and lead to pain, infection, and impaired quality of life. Current wound sealing technologies for chronic wound care remain largely palliative, with poor adhesion, weak mechanical properties, and limited ability to deliver therapeutics. Emerging technologies, including autologous blood products, growth factor-enhanced scaffolds, and artificial skin, although clinically successful, are limited from widespread adoption by the high cost of production and challenging clinical workflow. Here, we present a tough adhesive-elastomer wound care technology that is mechanically robust to approximate wound edges, can adhere strongly to wet and dynamic wound surfaces, is capable of delivering antimicrobials, and supports cell migration and proliferation. This technology has the potential to address an unmet clinical need in wound healing.

The prevalence of musculoskeletal diseases such as osteoarthritis, osteoporosis, sarcopenia, and rheumatoid arthritis is rising sharply with global ageing, increasing disability rates among older adults (aged ≥60 years), diminishing quality of life, and burdening health-care systems. Current musculoskeletal care for older adults faces multiple limitations, including comorbidities, frailty, and fragmented care. High osteoarthritis prevalence in individuals older than 55 years, the mounting economic burden of osteoporotic fractures, the growing concern of muscle mass decline, and insufficient guideline implementation collectively underscore these challenges. In the USA, musculoskeletal diseases affect over 121 million people and account for the highest rate of disability among all disease groups, underscoring the need for targeted strategies. Although promising solutions encompassing advanced pharmacological therapies, regenerative medicine, and digital health technologies (including artificial intelligence) are available, they remain underutilised in existing care models. This Personal View discusses the need for personalised, multidisciplinary approaches to address these issues, advocating for collaboration among the orthopaedic, geriatric, and health-care sectors in the USA. We propose that prevention of musculoskeletal diseases is key to its effective management in ageing populations, alongside a holistic, scalable approach that integrates diagnostics, therapy, and telemedicine. Early intervention, interdisciplinary collaboration, and personalised care are essential to improving patient outcomes and addressing the growing musculoskeletal disease burden in the USA.

Background: Autogenous bone grafts are the gold standard for reconstructing critical-sized bone defects in oral and maxillofacial surgery (OMS) but have limitations such as donor site morbidity. Bone tissue engineering (BTE) offers a promising alternative, with 3D-printing enabling precise scaffold design. The influence of scaffold architecture on osteogenesis, however, requires further exploration.

Aim: This study evaluates the impact of two 3D-printed β-tricalcium phosphate (β-TCP) scaffold architectures, with 500 µm and 1000 µm macropores, on cell proliferation, osteogenic differentiation, and ex vivo bone formation in a dynamic culture.

Both rigid plastics and soft hydrogels find ample applications in engineering and medicine but bear their own disadvantages that limit their broader applications. Bonding these mechanically dissimilar materials may resolve these limitations, preserve their advantages, and offer new opportunities as biointerfaces. Here, a robust adhesion strategy is proposed to integrate highly entangled tough hydrogels and diverse plastics with high interfacial adhesion energy and strength. Systemic investigations on the effects of hydrogel monomer content and crosslink fraction revealed the significant contributions of both polymer physical entanglements and interfacial covalent bonding. This hybrid engineering strategy also enables the plastic-hydrogel composite to attenuate foreign body response caused by pristine rigid plastics in vivo in mice. This versatile materials engineering approach may be broadly applicable to other polymer-based devices commonly used in regenerative medicine and surgical robotics.

Honey has been used as an empirical wound care agent for thousands of years and continues to be investigated and used in chronic wound care. In the past few years, several commercially available medical grade honey-based products have been approved for chronic wound therapy. Clinical trials showed that the therapeutic benefit of honey depends on wound type and honey composition. Recent insights into the pharmacology of honey in wound therapy over the past two decades have led to increased interest in this natural remedy and highlighted various antimicrobial and immunomodulatory properties that contribute to its pharmacologic action. However, the interaction between honey and the wound microenvironment on wound healing remains unclear. In this perspective, the current clinical evidence supporting the use of honey in wound care is presented and highlights its molecular mechanisms of action to eventually critically discuss the opportunities and challenges of using honey in wound care.

Surgical sutures are gold-standard wound closure devices. However, they are unable to form a tight seal with surrounding tissues, raising the risks of body fluid leakage and surgical site infection. Additionally, the use of sutures can result in cracking at suture roots, damage and micro-trauma to soft tissues due to the slicing and compression of suture fibers after their placement. Bioadhesives capable of mimicking natural biological interfaces are appealing alternatives, but they cannot achieve the same level of strength as conventional surgical sutures. Here, a tough adhesive puncture sealing (TAPS) suture, featuring swelling-triggered bioadhesion to mend the gap between the suture and the surrounding tissues with a soft yet tough adhesive interface is reported. This unique design principle of TAPS sutures is applicable to diverse soft tissues of various defect sizes and can be controlled by modulating the hydrogel swelling kinetics. The advantages of the TAPS sutures for meniscal tear repair and intestine tissue sealing ex vivo, corroborates their favorable applications in managing mechanically active musculoskeletal and gastrointestinal tissues are demonstrated. The design and performance of the TAPS sutures offer extensive possibilities for redesigning surgical tools and developing next-generation medical devices for wound management and tissue repair.

Micro-CT imaging of the hybrid hydrogel actuator (HHA) prototype showcasing its robust, flexible adhesion to tissue during dynamic actuation. This device enables tunable, mechanoresponsive drug delivery directly to the target site, presenting a transformative approach that integrates precisely controlled drug delivery with mechanical stimulation for enhanced localized therapeutic interventions. More details can be found in article number 2303301 by Ellen T. Roche and colleagues.

A tendon’s ordered extracellular matrix (ECM) is essential for transmitting force but is also highly prone to injury. How tendon cells embedded within and surrounding this dense ECM orchestrate healing is not well understood. Here, we identify a specialized quiescent Scx⁺/Axin2⁺ population in mouse and human tendons that initiates healing and is a major functional contributor to repair. Axin2⁺ cells express stem cell markers, expand in vitro, and have multilineage differentiation potential. Following tendon injury, Axin2⁺-descendants infiltrate the injury site, proliferate, and differentiate into tenocytes. Transplantation assays of Axin2-labeled cells into injured tendons reveal their dual capacity to significantly proliferate and differentiate yet retain their Axin2⁺ identity. Specific loss of Wnt secretion in Axin2⁺ or Scx⁺ cells disrupts their ability to respond to injury, severely compromising healing. Our work highlights an unusual paradigm, wherein specialized Axin2⁺/Scx⁺ cells rely on self-regulation to maintain their identity as key organizers of tissue healing.

Complete sequestration of central nervous system tissue and cerebrospinal fluid by the dural membrane is fundamental to maintaining homeostasis and proper organ function, making reconstruction of this layer an essential step during neurosurgery. Primary closure of the dura by suture repair is the current standard, despite facing technical, microenvironmental, and anatomic challenges. Here, we apply a mechanically tough hydrogel paired with a bioadhesive for intraoperative sealing of the dural membrane in rodent, porcine, and human central nervous system tissue. Tensile testing demonstrated that this dural tough adhesive (DTA) exhibited greater toughness with higher maximum stress and stretch compared with commercial sealants in aqueous environments. To evaluate the performance of DTA in the range of intracranial pressure typical of healthy and disease states, ex vivo burst pressure testing was conducted until failure after DTA or commercial sealant application on ex vivo porcine dura with a punch biopsy injury. In contrast to commercial sealants, DTA remained adhered to the porcine dura through increasing pressure up to 300 millimeters of mercury and achieved a greater maximum burst pressure. Feasibility of DTA to repair cerebrospinal fluid leak in a simulated surgical context was evaluated in postmortem human dural tissue. DTA supported effective sutureless repair of the porcine thecal sac in vivo. Biocompatibility and adhesion of DTA was maintained for up to 4 weeks in rodents after implantation. The findings suggest the potential of DTA to augment or perhaps even supplant suture repair and warrant further exploration.

Medical adhesives are emerging as an important clinical tool as adjuvants for sutures and staples in wound closure and healing and in the achievement of hemostasis. However, clinical adhesives combining cytocompatibility, as well as strong and stable adhesion in physiological conditions, are still in demand. Herein, a mussel-inspired strategy is explored to produce adhesive coacervates using tannic acid (TA) and methacrylate pullulan (PUL-MA). TA|PUL-MA coacervates mainly comprise van der Waals forces and hydrophobic interactions. The methacrylic groups in the PUL backbone increase the number of interactions in the adhesives matrix, resulting in enhanced cohesion and adhesion strength (72.7 Jm⁻²), compared to the non-methacrylated coacervate. The adhesive properties are kept in physiologic-mimetic solutions (72.8 Jm⁻²) for 72 h. The photopolymerization of TA|PUL-MA enables the on-demand detachment of the adhesive. The poor cytocompatibility associated with the use of phenolic groups is here circumvented by mixing reactive oxygen species-degrading enzyme in the adhesive coacervate. This addition does not hamper the adhesive character of the materials, nor their anti-microbial or hemostatic properties. This affordable and straightforward methodology, together with the tailorable adhesivity even in wet environments, high cytocompatibility, and anti-bacterial activity, enables foresee TA|PUL-MA as a promising ready-to-use bioadhesive for biomedical applications.