Mussel-inspired photothermal antibacterial multi-network hydrogel for cascade-enhanced infected wound healing.

ABSTRACTThe treatment of chronic wounds in the Aged is often difficult. Masquelet technique is used for the treatment of infected large segmental bone defects as it provides an adequate blood supply for bone and soft tissue reconstruction. In this study, a two‐stage wound management strategy was used, consisting of covering the initial wound with bone cement and skin grafting under induced membranes. From September 2020 to September 2022, 20 Aged patients with chronic refractory wounds of the lower extremities with exposed bone or tendons were recruited in the Department of Wound Repair Surgery of the Second Affiliated Hospital of Wenzhou Medical University. Each patient was reconstructed according to a two‐stage process. In the first stage, while treating the patient's underlying disease, several debridements were first performed on the wound; subsequently, the Masquelet technique was applied to seal the wound with antibiotic bone cement. Four to 6 weeks later, the second stage was initiated—after confirming the sufficient formation of wound induced membranes, the bone cement was removed, and free skin grafts were finally used to cover the chronic refractory wounds on the extremities. The area of the defects ranged from 4.5 × 3.0 cm to 15.0 × 6.0 cm, and all soft tissue defects were associated with tendon or bone exposure. After the surgery, patients attended regular outpatient visits and were followed up by telephone and video to observe the healing of the wounds and whether there were any complications in the donor site. The Lower Extremity Function Scale (LEFS) score was used to evaluate the functional recovery of the lower extremities. We found that all implants survived without necrosis or infection. All 20 cases were followed up regularly after surgery for 3 to 12 months, with a mean of 7.6 months. In the first stage, Induced Membranes induction was performed 1–4 times, with an average of (1.3 ± 0.7) times, and in the second stage, free skin grafting was performed on the induction membrane, and all 20 cases of skin grafting survived without necrosis or infection; the appearance and texture of the skin in the grafted area were satisfactory, and the postoperative LEFS score was (69.83 ± 10.82). Finally, our strategy for the management of chronic refractory wounds in the Aged can achieve satisfactory clinical results, reduce surgical risk, be simple and reliable, and be an effective addition to the repair modality.

In free flap reconstruction of the occipital region, the occipital artery can be a recipient vessel for vascular anastomosis, but few detailed reports or studies on its role as a recipient vessel are available. The authors report the case of a 74-year-old man in whom the occipital artery was used as the recipient vessel in occipital free tissue reconstruction. By using the occipital artery as the recipient vessel, tumor resection, latissimus dorsi myocutaneous flap harvesting, vascular anastomosis, and wound closure could all be completed with the patient in the prone position and without change of position. The authors consider the occipital artery to be a reliable recipient vessel that has a certain diameter and can secure a long vascular pedicle. Avoiding change of position with the brain exposed not only reduces the risk of infection but also shortens the overall surgical time.

Conductive hydrogels (CHs), which integrate the biomimetic properties of hydrogels with the functionality of conductive components, have demonstrated distinctive advantages in biomedical engineering. By modulating cell-cell interactions, CHs provide an optimal microenvironment to facilitate cellular growth, proliferation, and migration, emerging as a promising platform for tissue engineering and regenerative medicine applications. This review systematically examines the intricate relationships among the composition, structure, and fabrication strategies of CHs, while highlighting their recent advancements in biomedical applications, including skin tissue regeneration, spinal cord injury repair, muscular tissue reconstruction, cardiac tissue engineering, and biosensing technologies. The design and synthesis of diverse CHs are introduced first, followed by a comprehensive summary of the common preparation methods. Furthermore, the current limitations of CHs in practical applications are critically analyzed, alongside perspectives on future developmental directions. By elucidating the interplay between material properties and biological functionality, this review aims to inspire interest in CHs and offer valuable insights for their rational design and application in next-generation biomedical innovations.

Background:Cartilage regenerative medicine presents promising therapeutic options; however, mature cartilage tissue reconstruction remains challenging. Although techniques for expanding chondrocytes are clinically available, the production of mature articular and auricular cartilage tissues remains to be achieved. Similarly, although epidermal sheets from cell cultures have been clinically used for skin regeneration, dermal tissue reconstruction remains elusive. This study aimed to develop a rotational culture method to produce cartilage and dermal tissue without scaffold materials.Methods:The articular and auricular cartilage and dermis were isolated from patients with polydactyly or accessory auricles. The chondrocytes and fibroblasts were transferred to culture vessels and subjected to different rotational culture conditions: lateral rotational to rapidly form sheets for articular cartilage, box rotational to thicken tissue for auricular cartilage, and bottom rotational to form large tissue sheets for dermal fibroblast and articular cartilage. Sections and cultured cells were subjected to hematoxylin–eosin, Alcian blue, and type I collagen staining.Results:The lateral rotational method produced articular cartilage-like sheets, as confirmed by Alcian blue staining, which identifies mucopolysaccharides that make up the cartilage matrix. The box rotational method produced auricular-like cartilage tissue from auricular chondrocytes, whereas the bottom rotational method produced dermal-like sheets expressing type I collagen from human skin fibroblasts. All tissues were produced without using scaffold materials through repeated cell seeding and culture rotation.Conclusions:The tissues produced without scaffolds exhibited properties suitable for clinical applications, including elasticity, stretchability, and suturing capability, demonstrating a potentially promising breakthrough in cell manipulation technology for cartilage and dermis.

3D bioprinting provides a wide avenue for designing complex and customized constructs for regenerative medicine. Bioink formulations in 3D bioprinting usually lack micrometer-sized and interconnected pores for the supply of nutrients and oxygen and biological communications with host tissues, thus limiting cellular activities and therapeutic efficacy. Herein, we present microfibrous pore-forming bioinks for fabricating microporous hydrogels that encapsulate cells for muscle tissue reconstruction. Using phase separation technology, a liquid porogen is embedded into gelatin-based bioinks to form microfibrous structures. Printing bioinks with shear stress enabled the orientation of microfibrous pores along the printing direction, which facilitated the orientation of printed cells and enhanced myoblast differentiation. Moreover, the porous 3D scaffold exhibited promising results in terms of supplying nutrients and oxygen to improve cell survival. Printed tissue constructs are successfully transplanted into muscle tissue defects. This approach holds immense potential for creating anisotropically oriented 3D tissue constructs for applications in cell transplantation, drug screening, and disease modelling.

GelMA hydrogels guide lineage-specific self-assembly of endothelial and interstitial cells into valve-mimetic tissue architectures.

A heterogeneous hydrogel patch with mechanical activity and bioactivity for chronic diabetic wound healing.

Rethinking the value of dynamic and static feature planes in 4D reconstruction of deformable tissues.

Background/Objectives: Heel reconstruction is a complex procedure that requires soft tissue reconstruction resistant to weight, pressure, and shear stress. Various flap reconstruction methods have been reported; among them, free fasciocutaneous flaps have advantages in terms of function and aesthetics, but also have challenges due to the longer operation time required and the possibility of failure. The primary aim of this study was to examine the functional outcomes of heel reconstruction using free lateral arm fasciocutaneous flaps after wide excision of heel skin cancer. Methods: Between January 2014 and December 2020, eight patients underwent wide excision of skin cancer and reconstruction of the heel with a lateral arm free flap. Perioperative clinical data and postoperative outcomes, including flap survival, complications, Lower Extremity Functional Scale (LEFS) score, and American Orthopaedic Foot and Ankle Society scale (AOFAS) score, were analyzed from clinical records. Functional assessments were performed at a minimum of 12 months postoperatively (mean 18.3 months, range 12–24 months) by a single blinded examiner who was not involved in the surgical procedures. Both preoperative and postoperative LEFS and AOFAS scores were recorded for comparison. Results: The mean size of the skin and soft tissue defect was 32 cm2, the mean duration of surgery was 179 (range: 160–215) minutes, and the mean duration of hospital stay after surgery was 17 (range: 14–19) days, with a mean follow-up period of 48 (range: 33–59) months. Among the eight patients, two had diabetes mellitus (25%), one had peripheral neuropathy (12.5%), and none had clinically significant peripheral vasculopathy. All flaps survived, with one congestive episode. Satisfactory aesthetic and functional results were observed in all patients. The mean preoperative LEFS score was 28 (SD ± 6.1), which improved significantly to a postoperative mean of 57 (SD ± 8.3). Similarly, the mean preoperative AOFAS score was 45 (SD ± 5.8), improving to a postoperative mean of 61 (SD ± 6.2). Minor donor site complications included hypertrophic scarring in two patients (25%) and transient sensory changes in the lateral arm region in three patients (38%), all of which resolved with conservative management. Conclusions: This research suggests that the lateral arm free flap can be considered a reliable option in heel reconstruction, resulting in acceptable functional and aesthetic outcomes. It provides excellent durability, with solid bony union and good contour in small to moderate-sized heel defect cases.

We present six cases of post-traumatic osteoarthritis of proximal interphalangeal joint with swan neck deformity and ulnar deviation treated by surface replacement arthroplasty and soft tissue reconstruction using the radial slip of flexor digitorum superficialis tendon.

The acquired flatfoot, often called progressive collapsing foot deformity, frequently includes attenuation or failure of the spring ligament. Reconstruction of the spring ligament has been proposed in conjunction with other bone and soft tissue reconstruction techniques. In this study, we compared a tendon-graft reconstruction with suture tape augmentation in a cadaveric flatfoot model. Eight matched-pair fresh-frozen cadaver feet underwent flatfoot creation and reconstruction. The feet were cyclically loaded with 16,000 cycles from 200 N to 1.5× body weight at 1 Hz. Each foot was randomly assigned to undergo either suture tape or tendon graft reconstruction. Radiographic parameters and foot motion were measured at baseline, following creation of the collapsed arch deformity, and after repair. The cadaveric flatfoot model was successfully created, demonstrated by significant (P < .05) changes in Meary angle (mean change = +9.4 ± 6.4 degrees), talonavicular coverage angle (mean change = +15.6 ± 9.2 degrees), medial cuneiform height (mean change = -6.6 ± 4.1 mm), and calcaneal pitch (mean change = -2.6 ± 2.2 degrees). The tendon graft repair had significant improvements compared with flatfoot in the Meary angle (mean change = -6.4 ± 3.6 degrees), talonavicular coverage angle (mean change = -6.4 ± 5.2 degrees), calcaneal pitch (mean change = +1.9 ± 1.7 degrees), and medial cuneiform height (mean change = +3.7 ± 2.4 mm). The suture tape repair had significant improvements compared with flatfoot of talonavicular coverage angle (mean change = -8.1 ± 4.1) and calcaneal pitch (mean change = +2.9 ± 0.6). Inversion and eversion data showed hindfoot motion preserved from native to repair conditions. In load-to-failure testing, the tendon graft group had 1 failure at the interference screw and 1 midsubstance failure of the tendon graft. The suture tape group had 3 failures at the interference screws and 1 failure of the suture tape. Both techniques restored arch alignment from the flatfoot condition and preserved hindfoot motion in a cadaveric flatfoot model. Both techniques may provide a viable approach to restore alignment during flatfoot reconstruction. Both were mechanically stable under cyclic loading in this cadaver model; the tendon graft technique has a theoretical benefit of biological incorporation.

Random-pattern skin flaps are widely employed in tissue reconstruction, however, their survival is frequently hindered by ischemia, leading to necrosis. Metabolic alterations have been implicated in playing critical roles in angiogenesis during tissue repair. Using RNA sequencing analysis in a mouse model, we identified significant disruptions in glutamine metabolism, which substantially impaired angiogenesis within random-pattern skin flaps. Although local glutamine repletion failed to alleviate ischemia, administering α-ketoglutarate (α-KG) markedly promoted angiogenesis, as evidenced at both gene and protein levels. In human umbilical vein endothelial cells,α-KG enhanced the stability of hypoxia-inducible factor (HIF-1) alpha through activation of the phosphoinositide 3-kinase (PI3K)-Akt signaling pathway. Notably, α-KG treatment improved flap viability by augmenting blood perfusion, an effect correlated with upregulation of vascular endothelial growth factor expression. Together, these results reveal a novel mechanism by which α-KG enhances random-pattern skin flap viability via promoting angiogenesis through the PI3K/Akt/HIF-1α pathway, offering promising therapeutic insights for improving flap survival.Supplementary InformationThe online version contains supplementary material available at 10.1186/s13619-025-00264-8.

Background:The gracilis muscle flap is valuable as a reconstructive option because of its reliable anatomy and minimal donor-site morbidity. The aim of this systematic review was to evaluate acute perioperative complications and long-term outcomes of the gracilis muscle flap in distal lower limb reconstruction following trauma, infections, or oncological resections.Methods:This review was registered with PROSPERO (CRD42023486475) and adhered to PRISMA guidelines. All primary studies on gracilis flaps for lower leg soft tissue reconstruction were included, excluding those with flap recipient sites above the knee, isolated tendon repair, or nonprimary research articles. Searches were performed across Ovid MEDLINE, Ovid Embase, Cochrane CENTRAL, and PubMed.Results:Fifty-eight articles involving 1232 patients who underwent lower extremity reconstruction with a gracilis flap were included. Indications for surgery were trauma (n = 146), diabetes (n = 116), oncological (n = 31), infection (n = 27), other (n = 2), and heterogeneous (n = 910). A total of 397 (32.2%) complications were reported. In heterogeneous studies, pooled proportions were 0.22 for acute postoperative complications, 0.17 for recipient-site events, and 0.12 for donor-site morbidity, with oncological and infection cases showing the highest complication rates. The most common complications for each category were total flap loss (79, 6.4%), recipient infection (14, 1.1%), and donor-site scarring (14, 1.1%).Conclusions:The gracilis flap is a reliable option for reconstructing a wide array of soft tissue defects of the distal lower extremity, with modifications to increase its coverage area. The long-term functional and aesthetic outcomes after gracilis flap reconstruction are undescribed.

HIGHLIGHTS- T. grandis leaf methanolic extract contains 82 compounds, with 17 being predominant.- Epigallocatechin 3-O cinnamate, epigallocatechin 3-O-p-coumarate, and tectograndinol predicted as the potential bioactive compounds in wound healing- Molecular docking suggests inhibitory activities against NF-κB, MMP-2, and MMP-9, and stimulatory activity against EGFR-1 that comparable to commercial drugs. ABSTRACTWound-healing process involves a physiological cascade to restore skin integrity, which includes inflammatory response, cell proliferation, and tissue reconstruction. Prolonged inflammation in wound-healing process may lead to a chronic wound stage. Proper wound care is needed to prevent wound-caused mortality. Several studies showed the potential of T. grandis leaf in wound-healing process. However, the bioactive compounds and the molecular mechanism of T. grandis leaf remains unknown. This study aimed to identify bioactive compounds and biological activity contained in T. grandis leaf extract as well as analyze its molecular mechanism in wound-healing process by conducting in silico study using NF-κB, MMP-2, MMP-9, and EGFR-1. Bioactive compounds of T. grandis leaf extract were identified with LC-MS. Three potential compounds, epigallocatechin 3-O cinnamate, epigallocatechin 3-O-p-coumarate, and tectograndinol, were selected based on the Pa score screening with the PASS prediction. Drug-likeness and pharmacokinetics properties of the selected compounds were virtually identified by SwissADME and Protox. The interactions of T. grandis bioactive compounds toward NF-κB, MMP-2, MMP-9, and EGFR-1 were compared to those of curcumin, phenytoin, and nitrofurazone as control. Molecular docking to identify the protein-ligand interaction was performed by Autodock Vina integrated in PyRx v.0.8. Among 82 bioactive compounds detected in the LC-MS analysis, epigallocatechin 3-O-cinnamate, epigallocatechin 3-O-p coumarate, and tectograndinol exhibited anti-inflammatory, antioxidant, free radical scavenger, and MMP-9 inhibitor activities. According to Lipinski’s rule of five, bioactive compounds are possible to be administered as medication. Molecular docking showed that bioactive compounds potentially bound to the active sites of NF-κB, MMP-2, and MMP-9, resulting in proteins inhibition. This study suggested that the wound-healing mechanism of T. grandis bioactive compounds were driven by EGFR-1 stimulation indicated by the ability of bioactive compounds to interact with EGFR-1 in similar manner to those of nitrofurazone. We concluded that bioactive compounds of T. grandis leaf extract has significant potential to be used as traditional wound treatment and therapy. These compounds demonstrated wound-healing activity in silico by interacting with the key molecular targets, including NF-κB, MMP-2, MMP-9, and EGFR-1.

Unplanned returns to the emergency department (RTED) and hospital readmissions after surgery are notable burdens on the healthcare system and markers of potential gaps in patient care. The objective of this study was to identify the risk factors associated with RTED and unplanned readmissions after pediatric orthopaedic surgery. A retrospective cohort study was conducted between 2017 and 2023 and included patients younger than 18 who underwent orthopaedic surgery at a single, large academic institution. Patient data included current procedural terminology code, demographics, body mass index, insurance, language, and case complexity proxied by work relative value units. Procedural categories were defined by Accreditation Council for Graduate Medical Education case log guidelines for pediatric orthopaedics using current procedural terminology codes. The primary outcomes were RTED and hospital readmission within 7, 30, and 90 days of the index procedure. Univariable and multivariable logistic regression analyses were done to identify notable predictors for each outcome. In total, 3,044 pediatric patients were included. In multivariable analysis, patients with Medicaid insurance had a higher odd of RTED at 30 days (odds ratio [OR] 2.26, P = 0.007) and 90 days (OR 2.39, P < 0.001), and a higher odd of readmission at 90 days (OR 3.82, P = 0.002). Hispanic ethnicity was associated with 90-day RTED (OR 1.54, P = 0.023). Black or African American race was associated with 7-day (OR 9.24, P = 0.012) and 30-day (OR 4.00, P = 0.013) readmission. After controlling for demographic variables, operations for infection (OR 15.3, P = 0.002) and soft tissue reconstruction (OR 5.45, P = 0.046) were associated with 7-day RTED. Spine deformity surgery was associated with 30-day (OR 12.0, P = 0.006) and 90-day (OR 5.19, P = 0.031) readmission. Medicaid insurance status and the type of surgical procedure (infection, spine deformity, or soft tissue reconstruction) may represent high-risk populations for postoperative RTED and readmission. These findings underscore the need for enhanced postoperative patient support programs to mitigate adverse outcomes.

The surgical treatment of severe Dupuytren contracture release remains a challenge. Although contracture recurrence is common after Dupuytren contracture release, treatments that focus on removing all diseased skin and tissue result in less recurrence and more durable results. In this article, we propose an innovative soft tissue reconstruction technique using a thin, pliable arterialized-venous flap for severe Dupuytren contracture after dermatofasciectomy. This approach aims to enhance both aesthetic and functional outcomes by providing vascularized, durable wound coverage and minimizing the risk of contracture recurrence. We have performed four arterialized-venous flaps for severe Dupuytren contracture in patients who were previously faced with the only surgical option of digit amputations. All arterialized-venous flaps survived without partial or total necrosis, and all patients demonstrated improved flexion contracture with no evidence of recurrence (average follow-up of 145.25 weeks). For patients with severe recurrent Dupuytren contracture or those with Dupuytren diathesis, which is associated with a poor prognosis, arterialized-venous flaps following dermatofasciectomy offers an advanced treatment option. This approach not only facilitates complete excision of the diseased skin and soft tissues but also provides well-vascularized, durable wound coverage, significantly reducing the risk of recurrent contracture.

The reconstruction of complex soft tissues, such as urethral and nerve tissues, requires constructs that integrate vascularization, lumen integrity, and innervation with clinically relevant mechanical and biophysical properties. Current tissue-engineered tubular constructs often fail due to limited strength, instability under physiological conditions, and insufficient electroactivity. This study demonstrates the unique role of carbon nanofibers (CNFs) in improving the structural fidelity of alginate-gelatin hydrogels for additive manufacturing (3D extrusion printing) and clinical applicability. CNF incorporation improved gel strength, viscoelasticity, printability, and buildability while tailoring stretchability, compressibility, swelling, degradation, antimicrobial activity, vascularization, and inflammatory response in 3D-printed scaffolds. In the 3.5D printing approach, the rapid transformation of flat sheets of the CNF-reinforced hydrogel inks to customized tubular constructs with lumen patency was accomplished. At 0.75% CNF addition, hydrogel inks showed a 1.57- and 2.5-fold improvement in viscoelastic range with respect to shear stress and shear strain and a 1.2-fold increase in elastic recoverability, alongside a 3.6-fold enhancement in fracture stress and a 2-fold increase in elastic modulus under uniaxial tension, and the highest electrical conductivity of 0.5 S/m. Micro-CT confirmed interconnected porous structures with pore volume fraction and pore tortuosity of 0.74 and 1.09, respectively. At the same time, the as-printed tubular grafts (3.8 cm in length, 3 mm internal diameter) exhibited smooth luminal surfaces (∼44-100 nm roughness). NIH-3T3 fibroblasts maintained >80% viability, while antimicrobial analysis revealed strong activity against E. coli and S. aureus. In vivo study in Wistar rats revealed normal regulation of different immune cell markers such as CD8, CD68, TNF-α, COX-2, and IL-6, shifting from acute to chronic inflammation and an ehnacement in vascularization by 30 days as evident from H&E, MTS, and vWF straining. No systemic toxicity in the vital organs was recorded. Collectively, these findings highlight CNF-reinforced alginate-gelatin hydrogels can serve as electroconductive, mechanically robust, and biologically responsive scaffolds with a translational potential for complex soft tissue regeneration.

BackgroundInfertility is a serious health issue that has social and economic impacts on families. The construction of a bioengineered testis as an alternative solution can enhance infertility treatment processes. The principles of tissue engineering are derived from the natural reconstruction and repair of tissues, where scaffolds, alongside cells and signaling molecules, play a key role. Therefore, the aim of this study is to prepare a decellularized testicular scaffold from mouse tissue based on a supercritical carbon dioxide protocol and to investigate its histological properties, cell viability, and compatibility.MethodsThe whole rat testis tissue was decellularized using 1% SDS as pretreatment, Ethanol 70% as Co-solvent and Supercritical Carbon Dioxide. Optimal acellular removal was confirmed through DNA content analysis and staining with Hematoxylin–Eosin. The preservation of extracellular matrix structures was evaluated through glycosaminoglycans (GAGs) extraction and histological staining techniques, including periodic acid-Schiff, aldehyde fuchsin, Alcian blue, Masson’s trichrome, and Scanning electron microscopy (SEM). Additionally, the cytotoxicity of the scaffold was assessed using the MTT assay.ResultsThe optimal protocol for decellularization was determined to involve a combination of 1% SDS for 8 h and Supercritical Carbon Dioxide at parameters of 200 bar pressure, 45 °C, and a duration of 5 h. Evidence provided by quantitative and qualitative assessments of DNA, GAGs, SEM, and histochemical analyses confirmed effective cellular removal while adequately preserving the extracellular matrix of the rat testis post-decellularization. Additionally, the biocompatibility of the prepared scaffold was established through MTT assay, indicating favorable biological compatibility.ConclusionDespite the fact that the supercritical carbon dioxide protocol alone was unable to produce a decellularized scaffold with the desired standard characteristics, its combined use with 1% SDS not only reduced the decellularization time compared to other methods but also effectively preserved the extracellular matrix structures.

Shape memory hydrogels in tissue engineering: Recent advances and challenges.