Search Results (18)

Background: Cigarette burns represent a well-established forensic indicator of inflicted injury, frequently encountered in cases of domestic violence. Clinical significance: Their morphological consistency and anatomical distribution offer valuable elements for differentiating between intentional and accidental trauma. Case Presentation: In this study, we report the case of a 40-year-old woman who presented with multiple cutaneous lesions attributed to repeated assaults by her intimate partner. The forensic medical examination revealed five discrete scars characterized by sharply demarcated borders, circular to oval shapes, and dimensions ranging from 0.7 to 1.5 cm. These lesions were anatomically located in regions not typically accessible for self-infliction. To reinforce the diagnostic interpretation and assess reproducibility, a controlled experimental protocol was conducted using porcine skin matrices. Cigarette burns were recreated under variable conditions of contact pressure and exposure duration. The lesions produced on the biological substrate exhibited morphological features consistent with those observed in the patient, suggesting compatibility with cigarette-induced thermal injury. Conclusions: These findings provide circumstantial support for the forensic interpretation but must be considered within the limitations of the experimental model. This integrated approach underscores the relevance of combining clinical forensic documentation with experimental validation to support medico-legal conclusions in cases of suspected interpersonal violence. Full article

Background and Objectives: Corneal opacity is the fifth global cause of blindness and moderate-to-severe visual impairment due to scar tissue formation. The purpose of this study is to provide an integrated overview of the current state of corneal engineering strategies focused on the comparison with healthy corneas. It aims to identify engineering strategies that would result in functional corneas, providing real alternatives to donor corneal transplants. Materials and Methods: systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and according to the protocol with the ID: CRD420250654641 at the PROSPERO database. The focus question, prompted by considering the shortage of human corneal grafts, was: what is the performance of bioengineered corneal grafts in experimental animal models when compared with healthy eyes in the restoration of corneal anatomy and function? Results: Incorporating human corneal epithelial cells w/ or w/o human corneal stromal stem cells into a gelatin methacrylate and polyethylene glycol diacrylate matrix emerges as the leading option for epithelial layer regeneration. Human and bovine decellularized corneas, porcine corneal ECM in Gelatin methacrylate, dual layered collagen vitrigel and tissue-engineered human anterior hemi-corneas have shown promise for simultaneous regeneration of the corneal stromal and epithelial layers. Corneal stromal tissue regeneration could be positively impacted by transplantation with grafts derived from aligned self-lifting analogous tissue equivalents and collagen-based hydrogels. Finally, scaffolds of silk fibroin and human purified type I collagen represent promising approaches for corneal endothelial regeneration, though their effectiveness is contingent upon integration with endothelial cells. Conclusions: Collectively, these findings contribute to the growing body of evidence supporting the potential of tissue-engineered corneal substitutes as viable therapeutic options for corneal blindness and vision impairment. Assessing the optical and functional properties of the regenerated cornea should be a cornerstone in all studies aiming to evaluate their clinical effectiveness. Full article

Ischemic heart disease remains the leading cause of cardiovascular mortality worldwide. In myocardial infarction (MI), extracellular vesicles (EVs)—particularly small EVs (sEVs)—transport therapeutic cargo such as miR-21-5p, which suppresses apoptosis, and other proteins, lipids, and RNAs that can modulate cell death, inflammation, angiogenesis, and remodeling. This review synthesizes recent mechanistic and preclinical evidence on native and engineered EVs for post-MI repair, mapping therapeutic entry points across the MI timeline (acute injury, inflammation, and healing) and comparing EV sources (stem-cell and non-stem-cell), administration routes, and dosing strategies. We highlight engineering approaches—including surface ligands for cardiac homing, rational cargo loading to enhance potency, and biomaterial depots to prolong myocardial residence—that aim to improve tropism, durability, and efficacy. Manufacturing and analytical considerations are discussed in the context of contemporary guidance, with emphasis on identity, purity, and potency assays, as well as safety, immunogenicity, and pharmacology relevant to cardiac populations. Across small- and large-animal models, EV-based interventions have been associated with reduced infarct/scar burden, enhanced vascularization, and improved ventricular function, with representative preclinical studies reporting approximately 25–45% relative reductions in infarct size in rodent and porcine MI models, despite substantial heterogeneity in EV sources, formulations, and outcome reporting that limits cross-study comparability. We conclude that achieving clinical translation will require standardized cardiac-targeting strategies, validated good manufacturing practice (GMP)-compatible manufacturing platforms, and harmonized potency assays, alongside rigorous, head-to-head preclinical designs, to advance EV-based cardiorepair toward clinical testing. Full article

Uncontrolled fibrosis via excess deposition of extracellular matrix (ECM) is a hallmark of hypertrophic scars and keloids. A decellularized ECM biomaterial from porcine small intestinal submucosa (SIS; Biodesign or BioD, Cook Biotech, Inc.) is widely used in clinical applications for tissue repair. The objective of the current study was to test the effects of BioD scaffolds, as compared with collagen constructs, on normal human skin (nFB) and keloid fibroblasts (kFBs). Immortalized human dermal fibroblasts (hFBs) and human keloid fibroblasts (hKFs) were utilized for all experiments. Cells were cultured either on BioD membranes or on collagen gel (used as a control). To investigate pro-fibrotic signaling pathways, real-time quantitative PCR (qPCR), ELISA, and gene knockdown studies were conducted on cultured cells. ECM gene expression array revealed that BioD significantly attenuated (p < 0.05) the expression of thrombospondin-1 and fibronectin-1, two drivers of fibrosis in nFB as well as kFB. BioD-repressed thrombospondin-1 and fibronectin-1 gene expression manifested as significant downregulation (n = 5–6; p < 0.05) of both proteins in nFB and kFB. The levels of latent transforming-growth factor (LAP-TGFβ-1) were markedly reduced (n = 5; p < 0.05) in both nFB and kFB cultured on BioD, but not the other constructs. Knockdown of FN1 using siRNA significantly attenuated (n = 5, p < 0.05) pro-fibrotic responses, including expression of Col1A1 and the levels of LAP-TGFβ-1 in nFB, suggesting that downregulation of FN1 by BioD is one of the primary underlying mechanisms of attenuated pro-fibrotic responses in keloid fibroblasts. This study reports that a decellularized ECM scaffold may significantly attenuate pro-fibrotic responses in both normal and keloid fibroblasts via TSP1 and FN1-dependent mechanisms. Full article

Despite significant advancements, prosthetic hernia repair continues to face unacceptably high complication rates. These likely stem from poor biological responses, such as stiff scar tissue leading to mesh shrinkage. To overcome these issues, the Stenting and Shielding (S&S) Hernia System, a newly designed 3D dynamic device, has been developed for dissection-free laparoscopic placement to permanently obliterate hernia defects. Unlike conventional meshes, this device induces a regenerative biological response, promoting viable tissue growth rather than fibrotic plaque formation. In a porcine experimental model, the S&S device demonstrated the development of a great amount of muscle fibers, alongside nervous and vascular structures, within well-perfused connective tissue. Histological analysis of biopsy specimens excised from the experimental animals revealed progressive muscle fiber maturation from early myocyte development in the short term to fully developed muscle bundles in the long term. The enhanced biological response observed with the S&S device suggests a promising shift in hernia repair, potentially reversing the degenerative processes of hernia formation and promoting tissue regeneration. The S&S Hernia System described here can be classified not merely as a conventional hernia implant, but as part of a new category of hernia devices: the dynamic regenerative scaffold. Full article

Peripheral nerve injuries (PNIs) are a significant clinical challenge, often resulting in persistent sensory and motor deficits despite surgical repair. Autologous nerve grafts remain the gold standard for repair; however, outcomes are frequently suboptimal due to donor site morbidity and inconsistent functional recovery. A major obstacle in nerve regeneration is the formation of postoperative adhesions and fibrosis, which impede healing and necessitate revision surgeries. Nerve protectors from biological, synthetic, and hybrid materials offer a promising tissue engineering strategy to enhance nerve regeneration. These protectors are applied as a protective barrier when a nerve is severed without the gap, allowing for direct repair. They provide mechanical support and reduce scarring. Biocompatible biological wraps, including vascularized fat flaps, vein wraps, collagen-based materials, human amniotic membrane (hAM), porcine small intestinal submucosa (PSIS), and chitosan, modulate immune responses and promote vascularization. Synthetic alternatives, like polycaprolactone (PCL), provide mechanical stability with controlled degradation. Hybrid wraps, such as PCL-amnion, combine the benefits of both. Despite optimistic results, the heterogeneity of study methodologies hinders direct comparisons and standardization. This review highlights the latest developments in nerve wraps, their clinical applications, limitations, and future potential, guiding clinicians in selecting the most appropriate materials for peripheral nerve repair. Full article

Backgrounds: Burn injuries present significant medical challenges due to their complexity in healing and potential for severe scarring. This study evaluates the efficacy of Manuka honey in accelerating burn wound healing compared to conventional antibiotic ointments. Methods: Using a porcine model resembling human skin, nine Landrace breed female pigs with standardized deep dermal burns were treated with either Manuka honey in alginate or a combination of antibiotic ointments. Wound healing was assessed through macroscopic evaluation, a histopathological analysis, and immunohistochemical staining over a 60-day period. Results: Our findings indicate that the Manuka honey treatment was associated with significantly increased collagen density in the treated wounds compared to the control group (p < 0.05). The immunohistochemical analysis revealed lower macrophage activity (Iba1 staining) and a reduction in Ki67 expression on days 10 and 17 in the Manuka honey group, suggesting a more rapid transition toward tissue remodeling. The quantitative analysis showed a trend toward delayed epithelialization and increased inflammation in the control group, while wounds treated with Manuka honey exhibited faster reepithelialization and improved epidermal regeneration. However, additional studies are required to further assess collagen fiber organization and overall dermal architecture. Conclusions: These findings support the potential of Manuka honey as a beneficial treatment for burn wound healing, with evidence of enhanced reepithelialization and collagen deposition. Further research, including clinical trials, is necessary to fully elucidate its role in clinical practice and optimize treatment protocols. Full article

Organoid technology, as an innovative approach in biomedicine, exhibits promising prospects in disease modeling, pharmaceutical screening, regenerative medicine, and oncology research. However, the use of tumor-derived Matrigel as the primary method for culturing organoids has significantly impeded the clinical translation of organoid technology due to concerns about potential risks, batch-to-batch instability, and high costs. To address these challenges, this study innovatively introduced a photo-crosslinkable hydrogel made from a porcine small intestinal submucosa decellularized matrix (SIS), fish collagen (FC), and methacrylate gelatin (GelMA). The cost-effective hydrogel demonstrated excellent biocompatibility, tunable mechanical properties, rapid gelation properties, and low immunogenicity. Importantly, the proliferation and differentiation capacities of small intestinal organoids cultured in hydrogel were comparable to those in Matrigel, with no significant disparity observed. Furthermore, after one week of transplantation in nude mice, the hydrogel–organoid complex exhibited sustained structural and functional stability while preserving the differentiation characteristics of small intestinal organoids. Our study also demonstrated the effective potential of FC/SIS/GelMA hydrogel in accelerating the repair process of small intestinal defects, reducing the area of scar formation, and promoting the regeneration of both intestinal villi and smooth muscle tissue. In summary, this study presents a novel protocol for culturing small intestinal organoids, offering potential implications for future clinical applications and serving as an experimental foundation for the development of tissue-engineered intestines based on small intestinal organoids. Full article

The aim of our study is to investigate the feasibility and outcomes of using a femtosecond laser (FSL) platform (Ziemer LDV Z8) for deep anterior lamellar keratoplasty (DALK), enabling the creation of mushroom-shaped graft–host junctions, lamellar cuts, and intrastromal tunnels, to facilitate the big bubble, in one step. We included wet lab experiments on nine porcine eyes to assess the laser accuracy and cuts depth using an anterior segment (AS) OCT. This was followed by an interventional prospective case series on 10 eyes with variant corneal pathologies. The Z8 system, with in-built intraoperative optical coherence tomography (iOCT), guided corneal scans and directed the cuts. ASOCT showed visible mushroom configurations, lamellar cuts, and tunnels. Deviations from the target were 1.6%, 2.6%, and 3.5%. Anterior lamellar removal was easy in all clinical cases, including corneal scarring. The intrastromal tunnel was found at the preset location and the mushroom configuration was acquired. A big bubble was achieved in all cases. Type 1, 2, and 3 bubbles were formed in eight, one, and one case, respectively. We describe a new approach to DALK in which the in-built iOCT-guided FSL enables safe, precise, controlled, and reproducible desired cuts in one step. The preliminary clinical outcomes were favorable. Full article

In this study, an ultrasound-assisted digestion method of a formic acid-decellularized extracellular matrix (dECM) of porcine skin was developed and optimized to form UdECM hydrogels for diabetic wound healing. Results demonstrated that ultrasonication improved the extraction rate of collagen from dECM samples, preserved the collagen content of dECM, reduced residual cells, and extracted greater DNA contents. Scanning electron microscope (SEM) analyses were performed, which demonstrated the optimal porosity on the surface and density of the cross-section in the hydrogel structure, which could control the release of growth factors embedded in UdECM hydrogels at desirable rates to boost wound healing. A wound-healing study was conducted with six different composite hydrogels, both empty materials and materials enriched with rat platelet-rich plasma (R-PRP), sacchachitin nanofibers (SCNFs), and TEMPO-oxidized sacchachitin in diabetic rats. The assessment based on scars stained with hematoxylin and eosin (H&E), Masson’s trichrome (MT), and a cluster of differentiation 31 (CD31) staining showed that the UdECM/SC/R-PRP treatment group had the most significant efficacy of promoting healing and even recovery of diabetic wounds to normal tissues. UdECM/R-PRP and UdECM/SCNFs demonstrated better healing rates than UdECM hydrogel scaffolds, which had only recovered 50% resemblance to normal skin. Treatment with both UdECM/TEMPO 050 and UdECM/TEMPO 050/R-PRP hydrogel scaffolds was ranked last, with even poorer efficacy than UdECM hydrogels. In summary, formulated UdECM and SCNF hydrogels loaded with PRP showed synergistic effects of accelerating wound healing and ultimately stimulating the wound to recover as functional tissues. This newly UdECM/SCNF composite hydrogel has promising potential for healing and regenerating diabetic wounds. Full article

Biomaterials may enhance neural repair after spinal cord injury (SCI) and testing their functionality in large animals is essential to achieve successful clinical translation. This work developed a porcine contusion/compression SCI model to investigate the consequences of myelotomy and implantation of fibrin gel containing biofunctionalized carbon microfibers (MFs). Fourteen pigs were distributed in SCI, SCI/myelotomy, and SCI/myelotomy/implant groups. An automated device was used for SCI. A dorsal myelotomy was performed on the lesion site at 1 day post-injury for removing cloths and devitalized tissue. Bundles of MFs coated with a conducting polymer and cell adhesion molecules were embedded in fibrin gel and used to bridge the spinal cord cavity. Reproducible lesions of about 1 cm in length were obtained. Myelotomy and lesion debridement caused no further neural damage compared to SCI alone but had little positive effect on neural regrowth. The MFs/fibrin gel implant facilitated axonal sprouting, elongation, and alignment within the lesion. However, the implant also increased lesion volume and was ineffective in preventing fibrosis, thus precluding functional neural regeneration. Our results indicate that myelotomy and lesion debridement can be advantageously used for implanting MF-based scaffolds. However, the implants need refinement and pharmaceuticals will be necessary to limit scarring. Full article

As much as half or more of deep partial-thickness burn wounds develop hypertrophic scarring and contracture. Once formed, treatments are only minimally effective. Pirfenidone (Pf), indicated for treatment of idiopathic pulmonary fibrosis, is an anti-inflammatory and anti-fibrotic small molecule that potentially can be repurposed as a preventative against scarring in burn wounds. We present a drug-in-matrix patch with a soft skin adhesive (SSA) wound-contacting layer for multi-day drug delivery of Pf into burn wounds at the point of injury. Our patch construction consists of an SSA adhesive layer (Liveo™ MG7-9850, Dupont, Wilmington, DE, USA) for wound fixation, an acrylic co-polymer drug matrix (DURO-TAK 87-2852, Henkel, Düsseldorf, Germany) as the drug (Pf) reservoir, and an outermost protective polyurethane backing. By employing a drug-in-matrix patch design, Pf can be loaded as high as 2 mg/cm². Compared to the acrylic co-polymer adhesive patch preparations and commercial films, adding an SSA layer markedly reduces skin stripping observed under scanning electron microscopy (SEM). Moreover, the addition of varying SSA thicknesses did not interfere with the in vitro release kinetics or drug permeation in ex vivo porcine skin. The Pf patch can be easily applied onto and removed from deep partial-thickness burn wounds on Duroc pigs. Continuous multi-day dosing of Pf by the patches (>200 μg/cm²/day) reduced proinflammatory biomarkers in porcine burn wounds. Pf patches produced by the manual laboratory-scale process showed excellent stability, maintaining intact physical patch properties and in vitro biological activity for up to one year under long-term (25 °C at 60% RH) and 6 months under accelerated (40 °C at 75% RH) test conditions. To manufacture our wound safe-and-extended-release patch, we present scale-up processes using a machine-driven automated roll-to-roll pilot scale coater. Full article

Myocardial Infarction (MI) occurs due to a blockage in the coronary artery resulting in ischemia and necrosis of cardiomyocytes in the left ventricular heart muscle. The dying cardiac tissue is replaced with fibrous scar tissue, causing a decrease in myocardial contractility and thus affecting the functional capacity of the myocardium. Treatments, such as stent placements, cardiac bypasses, or transplants are beneficial but with many limitations, and may decrease the overall life expectancy due to related complications. In recent years, with the advent of human induced pluripotent stem cells (hiPSCs), newer avenues using cell-based approaches for the treatment of MI have emerged as a potential for cardiac regeneration. While hiPSCs and their derived differentiated cells are promising candidates, their translatability for clinical applications has been hindered due to poor preclinical reproducibility. Various preclinical animal models for MI, ranging from mice to non-human primates, have been adopted in cardiovascular research to mimic MI in humans. Therefore, a comprehensive literature review was essential to elucidate the factors affecting the reproducibility and translatability of large animal models. In this review article, we have discussed different animal models available for studying stem-cell transplantation in cardiovascular applications, mainly focusing on the highly translatable porcine MI model. Full article

Hypertrophic scars continue to be a major burden, especially after burns. Persistent inflammation during wound healing appears to be the precipitating aspect in pathologic scarring. The lack of a standardized model hinders research from fully elucidating pathophysiology and therapy, as most therapeutic approaches have sparse evidence. The goal of this project was to investigate the mechanisms of scar formation after prolonged wound inflammation and to introduce a method for generating standardized hypertrophic scars by inducing prolonged inflammation. Four wound types were created in Duroc pigs: full-thickness wounds, burn wounds, and both of them with induced hyperinflammation by resiquimod. Clinical assessment (Vancouver Scar Scale), tissue oxygenation by hyperspectral imaging, histologic assessment, and gene expression analysis were performed at various time points during the following five months. Native burn wounds as well as resiquimod-induced full-thickness and burn wounds resulted in more hypertrophic scars than full-thickness wounds. The scar scale showed significantly higher scores in burn- and resiquimod-induced wounds compared with full-thickness wounds as of day 77. These three wound types also showed relative hypoxia compared with uninduced full-thickness wounds in hyperspectral imaging and increased expression of HIF1a levels. The highest number of inflammatory cells was detected in resiquimod-induced full-thickness wounds with histologic features of hypertrophic scars in burn and resiquimod-induced wounds. Gene expression analysis revealed increased inflammation with only moderately altered fibrosis markers. We successfully created hypertrophic scars in the Duroc pig by using different wound etiologies. Inflammation caused by burns or resiquimod induction led to scars similar to human hypertrophic scars. This model may allow for the further investigation of the exact mechanisms of pathological scars, the role of hypoxia and inflammation, and the testing of therapeutic approaches. Full article

Researchers have shown that adult zebrafish have the potential to regenerate 20% of the ventricular muscle within two months of apex resection, and neonatal mice have the capacity to regenerate their heart after apex resection up until day 7 after birth. The goal of this study was to determine if large mammals (porcine heart model) have the capability to fully regenerate a resected portion of the left ventricular apex during the neonatal stage, and if so, how long the regenerative potential persists. A total of 36 piglets were divided into the following groups: 0-day control and surgical groups and seven-day control and surgical groups. For the apex removal groups, each piglet was subjected to a partial wall thickness resection (~30% of the ventricular wall thickness). Heart muscle function was assessed via transthoracic echocardiograms; the seven-day surgery group experienced a decrease in ejection fraction and fractional shortening. Upon gross necropsy, for piglets euthanized four weeks post-surgery, all 0-day-old hearts showed no signs of scarring or any indication of the induced injury. Histological analysis confirmed that piglets in the 0-day surgery group exhibited various degrees of regeneration, with half of the piglets showing full regeneration and the other half showing partial regeneration. However, each piglet in the seven-day surgery group demonstrated epicardial fibrosis along with moderate to severe dissecting interstitial fibrosis, which was accompanied by an abundant collagenous extracellular matrix as the result of a scar formation in the resection site. Histology of one 0-day apex resection piglet (briefly lain on and accidentally killed by the mother sow three days post-surgery) revealed dense, proliferative mesenchymal cells bordering the fibrin and hemorrhage zone and differentiating toward immature cardiomyocytes. We further examined the heart explants at 5-days post-surgery (5D PO) and 1-week post-surgery (1W PO) to assess the repair progression. For the 0-day surgery piglets euthanized at 5D PO and 1W PO, half had abundant proliferating mesenchymal cells, suggesting active regeneration, while the other half showed increased extracellular collagen. The seven-day surgery piglets euthanized at 5D PO, and 1W PO showed evidence of greatly increased extracellular collagen, while some piglets had proliferating mesenchymal cells, suggesting a regenerative effort is ongoing while scar formation seems to predominate. In short, our qualitative findings suggest that the piglets lose the full myocardial regenerative potential by 7 days after birth, but greatly preserve the regenerative potential within 1 day post-partum. Full article