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Complete wound healing without scar formation has attracted increasing attention, prompting the development of various strategies to address this challenge. In clinical settings, there is a growing preference for emerging biomedical technologies that effectively manage fibrosis following skin injury, as they provide high efficacy, cost-effectiveness, and minimal side effects compared to invasive and costly surgical techniques. This review gives an overview of the latest developments in advanced biomedical technologies for scarless wound management. We first introduce the wound healing process and key mechanisms involved in scar formation. Subsequently, we explore common strategies for wound treatment, including their fabrication methods, superior performance and the latest research developments in this field. We then shift our focus to emerging biomedical technologies for scarless wound healing, detailing the mechanism of action, unique properties, and advanced practical applications of various biomedical technology-based therapies, such as cell therapy, drug therapy, biomaterial therapy, and synergistic therapy. Finally, we critically assess the shortcomings and potential applications of these biomedical technologies and therapeutic methods in the realm of scar treatment.

In the study, we have shown the efficacy of an indigenously developed redox balancing chitosan gel with impregnated citrate capped Mn3O4 nanoparticles (nanogel). Application of the nanogel on a wound of preclinical mice model shows role of various signaling molecules and growth factors, and involvement of reactive oxygen species (ROS) at every stage, namely hemostasis, inflammation, and proliferation leading to complete maturation for the scarless wound healing. While in vitro characterization of nanogel using SEM, EDAX, and optical spectroscopy reveals pH regulated redox buffering capacity, in vivo preclinical studies on Swiss albino involving IL‐12, IFN‐γ, and α‐SMA signaling molecules and detailed histopathological investigation and angiogenesis on every stage elucidate role of redox buffering for the complete wound healing process. [ABSTRACT FROM AUTHOR]

Hypoxia, excessive reactive oxygen species (ROS), and impaired angiogenesis are prominent obstacles to wound healing following trauma and surgical procedures, often leading to the development of keloids and hypertrophic scars. To address these challenges, a novel approach has been proposed, involving the development of a cascade enzymatic reaction-based nanocarriers-laden wound dressing. This advanced technology incorporates superoxide dismutase modified oxygen nanobubbles and catalase modified oxygen nanobubbles within an alginate hydrogel matrix. The oxygen nano chamber functions through a cascade reaction between superoxide dismutase and catalase, wherein excessive superoxide in the wound environment is enzymatically decomposed into hydrogen peroxide, and this hydrogen peroxide is subsequently converted into oxygen by catalase. This enzymatic cascade effectively controls wound inflammation and hypoxia, mitigating the risk of keloid formation. Concurrently, the oxygen nanobubbles release oxygen continuously, thus providing a sustained supply of oxygen to the wound site. The oxygen release from this dynamic system stimulates fibroblast proliferation, fosters the formation of new blood vessels, and contributes to the overall wound healing process. In the rat full-thickness wound model, the cascade reaction-based nano oxygen chamber displayed a notable capacity to expedite wound healing without scarring. Furthermore, in the pilot study of porcine full-thickness wound healing, a notable acceleration of tissue repair was observed in the conceived cascade reaction-based gel treated group within the 3 days post-surgery, which represents the proliferation stage of healing process. These achievements hold significant importance in ensuring the complete functional recovery of tissues, thereby highlighting its potential as a promising approach for enhancing wound healing outcomes.

The drug‐resistant bacterial‐infected skin wound is still a severe healthcare problem. Uncontrolled bacterial infection, abundant reactive oxygen species (ROS) content, and prolonged inflammatory response are detrimental to wound healing. Moreover, excessive vessel growth can result in unsatisfactory scar formation. Herein, a three‐step regenerative strategy based on a bilayered gelatin/acryloyl β‐cyclodextrin (BGACD) hydrogel containing physical host–guest complexations and chemical crosslinks is proposed. The hydrogel is loaded with humic acids (HAs) and astragaloside IV (AS) in the lower layer and verteporfin (Vt) in the upper layer. Different gelatin/acryloyl β‐cyclodextrin ratios endow the lower and upper layers of the hydrogel with different degradation rates. Under light irradiation, the combination of HAs‐induced photothermal therapy (PTT) and verteporfin‐induced photodynamic therapy effectively inhibits MRSA growth. The HAs and astragaloside IV are released from the lower layer to scavenge ROS and promote M2 macrophage polarization and angiogenesis during the inflammation and early proliferation phases, while verteporfin releases from the upper layer suppress excessive vessel growth during the late proliferation and remodeling phases. The HAs‐AS@Vt@BGACD hydrogel successfully achieves rapid and scarless wound healing in an MRSA‐infected wound model in rats. Therefore, the HAs‐AS@Vt@BGACD hydrogel shows promising potential for the treatment of drug‐resistant bacteria‐infected skin wound healing. [ABSTRACT FROM AUTHOR]

Abstract Wound healing is a common occurrence. However, delayed healing and aberrant scarring result in pathological wound healing. Accordingly, a scarless wound healing remains a significant clinical challenge. In this study, we constructed hyaluronic acid (HA)-modified and verteporfin (VP)-loaded polylactic acid (PLA) nanogels (HA/VP-PLA) to promote scarless wound healing by accelerating wound re-epithelialization and controlling scar formation. Owing to the unique structure of HA incorporating and coating in VP-loaded PLA nanoparticles, HA/VP-PLA could be topically applied on wound to achieve targeted delivery to fibroblasts. Then, HA/VP-PLA released HA and lactic acid (LA) to stimulate the proliferation and migration of fibroblasts, as well as VP to inhibit Yes-associated protein (YAP) expression and nuclear localization to suppress fibrosis. In vitro (skin fibroblasts) and in vivo (rat and rabbit models) experiments strongly suggested that HA/VP-PLA promoted scarless wound healing by accelerating wound re-epithelialization and controlling scar formation. Therefore, our work provides a feasible strategy for scarless wound healing, and the sophisticated HA/VP-PLA exhibit a great potential for clinical applications.

The revolutionary role of tissue adhesives in wound closure, tissue sealing, and bleeding control necessitates the development of multifunctional materials capable of effective and scarless healing. In contrast to the use of traditionally utilized toxic oxidative crosslinking initiators (exemplified by sodium periodate and silver nitrate), herein, the natural polyphenolic compound tannic acid (TA) was used to achieve near instantaneous (90% bacterial death upon near-infrared (NIR) irradiation). In vivo evaluation in both an infected full-thickness skin wound model and a rat skin incision model demonstrated that 3A-TCMBAs + NIR treatment could promote wound closure and collagen deposition and improve the collagen I/III ratio on wound sites while simultaneously inhibiting the expression of pro-inflammatory cytokines. Further, phased angiogenesis was observed via promotion in the early wound closure phases followed by inhibition and triggering of degradation & remodeling of the extracellular matrix (ECM) in the late stage (supported by phased CD31 (platelet endothelial cell adhesion molecule-1) PDGF (platelet-derived growth factor) and VEGF (vascular endothelial growth factor) expression as well as elevated matrix metalloprotein-9 (MMP-9) expression on day 21), resulting in scarless wound healing. The significant convergence of material and bioactive properties elucidated above warrant further exploration of 3A-TCMBAs as a significant, new class of bioadhesive.

Moderately regulating vascularization and immune microenvironment of wound site is necessary to achieve scarless wound healing of the skin. Herein, we have prepared an angiogenesis-promoting and scar-preventing band-aid with a core-shell structure, that consists of MXene-loaded nanofibers (MNFs) as the core and dopamine-hyaluronic acid hydrogel (H) as the shell (MNFs@V–H@DA) to encapsulate a growth factor (vascular endothelial growth factor, VEGF, abbreviated as V) and H2S donor (diallyl trisulfide, DATS, abbreviated as DA). The continuous release of DA from this system produced H2S, which would successfully induce macrophages to polarize into M2-lile phenotype, regulating the immune microenvironment and inhibiting an excessive inflammatory response at the wound sites. It is conducive to the proliferation of skin cells, facilitating the wound healing. In addition, an appropriate amount of VEGF can be released from the MXene nanofibrous skeleton by adjusting the time of near-infrared (NIR) light exposure, preventing excessive neovascularization and extracellular matrix deposition at the wound sites. Collectively, this NIR photothermal-responsive band-aid achieved scarless wound healing through gradient-controlled vascularization and a related immune sequential reaction of damaged skin tissue.

The quest for scarless wound healing is imperative in healthcare, aiming to diminish the challenges of conventional wound treatment. Hyaluronic acid (HA), a key component of the skin's extracellular matrix, plays a pivotal role in wound healing and skin rejuvenation. Leveraging the advantages of HA hydrogels, this research focuses first on tuning the physicochemical and mechanical properties of photo-crosslinkable methacrylated HA (MAHA) by varying the methacrylation degree, polymer concentration, photo-crosslinker concentration, and UV exposure time. The optimized hydrogel, featuring suitable porosity, swelling ratio, degradability, and mechanical properties, was then used for the combined delivery of tannic acid (TA), known for its hemostatic, antibacterial, and antioxidant properties, and Wharton's jelly-derived mesenchymal stem cells (WJ-MSCs) cultured on the MAHA-TA hydrogel to enhance skin regeneration. The composite MAHA-TA-MSC hydrogel demonstrated favorable pores and biocompatibility, evidenced by cell viability, and promoted cell proliferation. When applied to dorsal wounds in rats, this composite hydrogel accelerated wound healing and reduced scarring. Additionally, molecular and histopathological analyses revealed increased expression of IL-10, the TGF-β3/TGF-β1 ratio, and the Collagen III/Collagen I ratio. These findings suggest that the MAHA-TA-MSC hydrogel is a promising candidate for scarless acute wound healing. [Display omitted] [ABSTRACT FROM AUTHOR]

Increased inflammatory responses and oxidative stress at the wound site following skin trauma impair healing. Furthermore, skin scarring places fibroblasts under severe mechanical stress and aggravates pathological fibrosis. A novel liposomal composite hydrogel is engineered for wound microenvironment remodeling, incorporating dual-loaded liposomes into gelatin methacrylate to create a nanocomposite hydrogel. Notably, tetrahydrocurcumin (THC) and hepatocyte growth factor (HGF) are encapsulated in the hydrophobic and hydrophilic layers of liposomes, respectively. The composite hydrogel maintains porous nanoarchitecture, demonstrating sustainable THC and HGF release and enhanced mechanical properties and biocompatibility. This system effectively promotes cell proliferation and angiogenesis and attenuates apoptosis. It decreases the expression of the inflammatory factors by inhibiting the high-mobility group box /receptor for advanced glycation end product/NF-κB (HMGB1/RAGE/NF-κB)pathway and increases macrophage polarization from M1 to M2 in vitro, effectively controlling inflammatory responses. It exhibits remarkable antioxidant properties by scavenging excess reactive oxygen species and free radicals. Most importantly, it effectively prevents scar formation by restraining the transforming growth factor beta (TGF-β)/Smads pathway that downregulates associated fibrotic factors. It demonstrates strong therapeutic effects against inflammation and fibrosis in a rat skin wound model with biosafety, advancing the development of innovative hydrogel-based therapeutic delivery strategies for clinical scarless wound therapy., (© 2024 Wiley‐VCH GmbH.)

Corneal defects can lead to stromal scarring and vision loss, which is currently only treatable with a cadaveric corneal transplant. Although in situ -forming hydrogels have been shown to foster regeneration of the cornea in the setting of stromal defects, the cross-linking, biomechanical, and compositional parameters that optimize healing have not yet been established. This, Corneal defects are also almost universally inflamed, and their rapid closure without fibrosis are critical to preserving vision. Here, an in situ forming, bioorthogonally cross-linked, nanocluster (NC)-reinforced collagen and hyaluronic acid hydrogel (NCColHA hydrogel) with enhanced structural integrity and both pro-regenerative and anti-inflammatory effects was developed and tested within a corneal defect model in vivo . The NCs serve as bioorthogonal nanocross-linkers, providing higher cross-linking density than polymer-based alternatives. The NCs also serve as delivery vehicles for prednisolone (PRD) and the hepatocyte growth factor (HGF). NCColHA hydrogels rapidly gel within a few minutes upon administration and exhibit robust rheological properties, excellent transparency, and negligible swelling/deswelling behavior. The hydrogel's biocompatibility and capacity to support cell growth were assessed using primary human corneal epithelial cells. Re-epithelialization on the NCColHA hydrogel was clearly observed in rabbit eyes, both ex vivo and in vivo , with expression of normal epithelial biomarkers, including CD44, CK12, CK14, α-SMA, Tuj-1, and ZO-1, and stratified, multilayered morphology. The applied hydrogel maintained its structural integrity for at least 14 days and remodeled into a transparent stroma by 56 days.

The developments of nanoparticle-based treatments that benefit from novel discoveries have an essential place in the regeneration of acute and chronic wounds. Furthermore, research about the treatment methods which attempt to swiftly and scarless wound recovery has increased over time. In recent years, it has been shown that metallic-based nanoparticles, especially silver and gold derived, have an accelerating effect on chronic and contaminated wound healing. The crucial factors of inducing and completion of regeneration of wound are enhanced epithelialization rate and neovascularization in the tissue. In our study, the main purpose is the investigation of the boosting effects of erbium borate nanoparticles on the wound healing process, especially scarless ones. Newly syntesized erbium borate nanoparticles (ErB-Nps) were characterized by their concentration and particle size using nanoparticle tracking analysis (NTA). In order to examine the effect of ErB-Np on wound closure, scratch assay for dermal epithelial cells and tube formation assay for endothelial cells were performed. In addition, in order to examine the effect of the ErB-Np at a molecular level, the levels of genes related to both wound healing, inflammation, and scarless wound closure were determined with the RT-PCR experiment. Consequently, it has been shown that erbium borate nanoparticles have increased the melioration speed of scar tissue and have given clues about scarless healing potential. The investigation of the regeneration potential of erbium borate nanoparticles was done via MTS assay, quantitative PCR analysis, reactive oxygen species assay, and scratch assay. Our results show that ErB-Np is a proper agent that can be used for scarless wound healing. [ABSTRACT FROM AUTHOR]

[Display omitted] • Electrical and immune stimulation-based hydrogels sHA/G-GM synergistically realize scarless wound healing. • sHA/G-GM modulate fibroblast activation via amplifying the endogenous electrophysiology. • sHA/G-GM modulate immune microenvironment via promoting macrophage phenotype-switching. Scars are a consequence of the wound healing process, and scarless wound healing remains a substantial clinical challenge. In this study, conductive hydrogels (named sHA/G-GM) were developed to synergistically realize scarless wound healing through electrical and immune stimulation. sHA/G-GM was prepared as high-sulfated hyaluronan (sHA) modified graphene (sHA/G) homodispersing in gelatin methacrylate, and sHA/G was released and absorbed by cytomembranes. In vitro (human scar fibroblasts and mouse primary macrophages) and in vivo (rat wound models and rabbit ear wound models) studies were conducted and demonstrated that sHA/G-GM not only improves conductivity to fibroblast activity regulation but also combines with interleukin-4 to promote macrophage phenotype switching. These results strongly suggest that sHA/G-GM synergistically amplifies endogenous electrophysiological functions and modulates the immune microenvironment to realize scarless wound healing. Therefore, the electrical and immune stimulation-based sHA/G-GM provide an effective approach to synergistically realize scarless wound healing in the future. [ABSTRACT FROM AUTHOR]

In recent years, research on wound healing has become increasingly in-depth, but therapeutic effects are still not satisfactory. Occasionally, pathological tissue repair occurs. Influencing factors have been proposed, but finding the turning point between normal and pathological tissue repair is difficult. Therefore, we focused our attention on the most basic level of tissue repair: fibroblasts. Fibroblasts were once considered terminally differentiated cells that represent a single cell type, and their heterogeneity was not studied until recently. We believe that subpopulations of fibroblasts play different roles in tissue repair, resulting in different repair results, such as the formation of normal scars in physiological tissue repair and fibrosis or ulcers in pathological tissue repair. It is also proposed that scarless healing can be achieved by regulating fibroblast subpopulations.

The purpose of the study was to determine the structural dynamics of healing and skin regeneration characteristics after thermal burns in laboratory rodents in an artificial local regeneration environment - the burn surface is protected by the dome of the device filled with regularly replaced sterile isotonic saline solution. The article presents characteristics of the inflammatory response reaction to steam burns and subsequent skin regeneration in the following comparative aspect: during natural healing under the eschar and in case of constant contact of the burn surface with solutions. Scientific novelty consists in the study of changes in the inflammatory and regenerative response depending on the state of state of aggregation of matter interacting with a wound. It was concluded that secondary skin alteration and fibrous changes in water environment are much lower with considerably higher degree of regeneration. These data can serve as the basis for new regenerative technologies in combustiology. [ABSTRACT FROM AUTHOR]

Adipose‐derived stem cells (ASCs) possess strong regenerative potencies and have been used to improve wound healing in animal models and clinical studies. However, the use of ASCs on scarless wound healing is not satisfactory. Matrix metalloproteinase 3 (MMP‐3) is involved in extracellular matrix (ECM) remolding and scar formation. We aimed to investigate the effect of ASCs stable expressing MMP‐3 (ASCs‐MMP‐3) on wound healing and scarring. A cutaneous wound healing animal model was used to assess the effect of ASCs and ASCs‐MMP‐3 on wound healing and scar formation. The target protein levels in the wound tissues were determined by western blot assay. Our results demonstrated that ASCs alone promoted wound healing but had a negligible effect on reducing scarring. ASCs‐MMP‐3 not only possessed the ability of ASCs to speed up wound healing, but also incorporated the capability of MMP‐3 to reduce scaring. Overexpressing of MMP‐3 decreased the collagen I, transforming growth factor (TGF)‐β1, and α‐smooth muscle actin (α‐SMA) levels and enhanced collagen III and TGF‐β3 levels which contributed to reducing scar formation. Our studies suggested that ASCs‐MMP‐3 is a potential candidate for developing effective therapeutic strategies for scarless wound healing. [ABSTRACT FROM AUTHOR]

Full-thickness skin defect has always been a major challenge in clinics due to fibrous hyperplasia in the repair process. Hydrogel composite dressings loaded with anti-fibrotic drugs have been considered as a promising strategy for scarless skin regeneration. In this work, a hydrogel composite (VP-CMCS-OSA) of carboxymethyl chitosan (CMCS) and oxidized sodium alginate (OSA), with loading anti-fibrotic drug verteporfin (VP), is developed based on two-step chemical reactions. Verteporfin is bonded with carboxymethyl chitosan through EDC/NHS treatment to form VP-CMCS, and then VP-CMCS is crosslinked with oxidized sodium alginate by Schiff base reaction to form VP-CMCS-OSA hydrogel. The characterization by SEM, FTIR, and UV-Vis shows the microstructure and chemical bonding of VP-CMCS-OSA. VP-CMCS-OSA hydrogel demonstrates the properties of high tissue adhesion, strong self-healing, and tensile ability. In the full-thickness skin defect model, the VP-CMCS-OSA composite hydrogels hasten wound healing due to the synergistic effects of hydrogels and verteporfin administration. The histological examination reveals the regular collagen arrangement and more skin appendages after VP-CMCS-OSA composite hydrogel treatment, indicating the full-thickness skin regeneration without potential scar formation. The outcomes suggest that the verteporfin-loaded composite hydrogel could be a potential method for scarless skin regeneration., (© 2023 Wiley-VCH GmbH.)

Although there are numerous medical applications to recover damaged skin tissue, scarless wound healing is being extensively investigated to provide a better therapeutic outcome. The exogenous delivery of therapeutic growth factors (GFs) is one of the engineering strategies for skin regeneration. This study presents an exogenous GF delivery platform developed using coacervates (Coa), a tertiary complex of poly(ethylene argininyl aspartate diglyceride) (PEAD) polycation, heparin, and cargo GFs (i.e. , transforming growth factor beta 3 (TGF-β3) and interleukin 10 (IL-10)). Coa encompasses the advantage of high biocompatibility, facile preparation, protection of cargo GFs, and sustained GF release. We therefore speculated that coacervate-mediated dual delivery of TGF-β3/IL-10 would exhibit synergistic effects for the reduction of scar formation during physiological wound healing. Our results indicate that the exogenous administration of dual GF via Coa enhances the proliferation and migration of skin-related cells. Gene expression profiles using RT-PCR revealed up-regulation of ECM formation at early stage of wound healing and down-regulation of scar-related genes at later stages. Furthermore, direct injection of the dual GF Coa into the edges of damaged skin in a rat skin wound defect model demonstrated accelerated wound closure and skin regeneration after 3 weeks. Histological evaluation and immunohistochemical staining also revealed enhanced formation of the epidermal layer along with facilitated angiogenesis following dual GF Coa delivery. Based on these results, we conclude that polycation-mediated Coa fabrication and exogenous dual GF delivery via the Coa platform effectively augments both the quantity and quality of regenerated skin tissues without scar formation. This study was conducted to develop a simple administration platform for scarless skin regeneration using polycation-based coacervates with dual GFs. Both in vitro and in vivo studies were performed to confirm the therapeutic efficacy of this platform toward scarless wound healing. Our results demonstrate that the platform developed by us enhances the proliferation and migration of skin-related cells. Sequential modulation in various gene expression profiles suggests a balanced collagen-remodeling process by dual GFs. Furthermore, in vivo histological evaluation demonstrates that our technique enhances clear epidermis formation with less scab and thicker woven structure of collagen bundle, similar to that of a normal tissue. We propose that simple administration of dual GFs with Coa has the potential to be applied as a clinical approach for fundamental scarless skin regeneration. [ABSTRACT FROM AUTHOR]

Scar formation during wound repair can be devastating for affected individuals. Our group previously documented the therapeutic potential of novel progenitor cell populations from the non-scarring buccal mucosa. These Oral Mucosa Lamina Propria-Progenitor Cells (OMLP-PCs) are multipotent, immunosuppressive, and antibacterial. Small extracellular vesicles (sEVs) may play important roles in stem cell-mediated repair in varied settings; hence, we investigated sEVs from this source for wound repair. We created an hTERT immortalized OMLP-PC line (OMLP-PCL) and confirmed retention of morphology, lineage plasticity, surface markers, and functional properties. sEVs isolated from OMLP-PCL were analyzed by nanoparticle tracking analysis, Cryo-EM and flow cytometry. Compared to bone marrow-derived mesenchymal stromal cells (BM-MSC) sEVs, OMLP-PCL sEVs were more potent at driving wound healing functions, including cell proliferation and wound repopulation and downregulated myofibroblast formation. A reduced scarring potential was further demonstrated in a preclinical in vivo model. Manipulation of OMLP-PCL sEVs may provide novel options for non-scarring wound healing in clinical settings., (© The Author(s) 2022. Published by Oxford University Press.)

Abstract: Purpose: During early gestation, fetal wounds heal with paucity of inflammation and absent scar formation. P-selectin is an adhesion molecule that is important for leukocyte recruitment to injury sites. We used a murine fetal wound healing model to study the specific contribution of P-selectin to scarless wound repair. Methods: Linear excisional wounds were created on the dorsa of E15.5 and E17.5 gestation fetuses in wild-type and P-selectin (-/-) mice (term = 19 days). Wounds were harvested at various time-points after wounding and analyzed using histology and immunohistochemistry. Results: The E15.5 wounds in both wild-type and P-selectin (-/-) fetuses healed scarlessly and with minimal inflammation, whereas E17.5 wounds healed with fibrosis and inflammation. However, the scars of the P-selectin (-/-) wounds appeared slightly different than wild-type. There were significantly more inflammatory cells in E17.5 wild-type wounds 6 hours after injury (P < .001), but the difference was no longer significant by 24 hours. Finally, reepithelialization was slower in the E15.5 knockout wounds compared to their wild-type counterparts. Conclusions: Absence of P-selectin delays inflammatory cell recruitment and reepithelialization of fetal wounds; however, scar formation still occurs in late gestation wounds. The contribution of specific molecules to fetal wound healing can be elucidated using murine knockout or transgenic models. [Copyright &y& Elsevier]

Objectives: Modulating cytokine signaling in vocal fold fibroblasts after injury may influence extracellular matrix (ECM) production and eventual fibrotic outcome. To evaluate previously established in vivo cytokine and ECM gene expression hypotheses, we examined in vitro vocal fold fibroblast responses to exogenous inflammatory factor stimulation. Methods: Rat vocal fold fibroblast lines derived from explants were separately treated with interleukin- 1β (IL-1β), interferon gamma (IFN-γ), tumor necrosis factor a (TNF-α), transforming growth factor β subtype 1 (TGF-β1), or prostaglandin E2 (PGE2). We examined the in vitro messenger RNA expression profiles of IL-1β, IFN-γ, TNF-α, TGF-β1, and cyclooxygenase 2 (COX-2), as well as those of hyaluronic acid synthase (HAS) 1, HAS-2, procollagen subtype 1, and procollagen subtype 3, at 1,4, 8, 16, 24, and 72 hours after treatment, and compared them to those of untreated fibroblasts and in vivo data, using real-time reverse transcription-polymerase chain reaction. Results: IL-1β and TNF-α induced each other and synergistically increased HAS-i and HAS-2 expression. PGE2 also up-regulated HAS-1 and HAS-2 expression. IFN-γ, IL-1β, TNF-α, and TGF-β1 up-regulated HAS expression alongside either transient up-regulation of, or no change in, procollagen 1 and 3 expression. Most treatments appeared to suppress procollagen expression, possibly through HAS up-regulation. All inflammatory factors attenuated TGF-β1 expression. Conclusions: These results confirm several in vivo trends, identify potential cytokine pathways and therapeutic candidates, and suggest the utility of this in vitro setup for future studies. [ABSTRACT FROM AUTHOR]

The ‘simple’ problem of fibrosis has a diverse public health impact ranging from disfiguring scarring, fibrosis of organs, visceral adhesions, mobility restriction and blindness. Both lay people and clinicians clearly recognize the phenotypic variation of cutaneous surgical outcomes ranging from keloids, hypertrophic scars, ‘normal’ scar formation and ‘scarless’ wound healing. By comparing the three major wound healing processes of inflammation, angiogenesis and fibrosis in the fetal and postnatal periods, clear differences are apparent in all three of these wound healing processes. The purpose of this review is to examine the current understanding of scarless wound healing and then to provide a perspective on the potential future application of these concepts to improve glaucoma filtration surgery outcomes. [ABSTRACT FROM AUTHOR]

[Display omitted] • Cationic silicone derivative QS14 was successfully synthesized and characterized. • The bilayered electrospun nanofibrous wound dressing PQCQS consisting of the outer layer PQS and the inner layer PCQC was prepared by electrospinning. • PQCQS exhibited the excellent physicochemical properties and good biocompatibility. • PQCQS could play a significant role of wound healing in the full-thickness skin defect rabbit ear model. The design of novel wound dressings with favorable mechanical properties, hemostasis, inherent antibacterial function, and biocompatibility to facilitate skin wound healing and inhibit scar formation has practical significance in clinical applications. Herein, a bilayered nanofibrous membrane (PQCQS) was fabricated by electrospinning poly(ε-caprolactone) (PCL)/quaternized silicone (PQS, outer layer) and polyvinyl alcohol/collagen/quaternized chitosan (PCQC, inner layer) as wound dressings for damaged skin. The PQS nanofiber was utilized as the outer layer of the wound dressing because it combined the good mechanical property of PCL and antibacterial performance of quaternized silicone to suppress scar formation and provide a stable microenvironment for the wound healing process. The inner membrane (PCQC) exhibited hydrophilicity, biocompatibility, and hemostasis, thus facilitating wound healing. The PQCQS membranes exhibited excellent hydrophilicity, outstanding thermal stability, comparable mechanical properties with human skin, efficient hemostatic performance, and cytocompatibility. Moreover, the PQCQS membranes demonstrated a good balance between antibacterial activity and cell proliferation. Moreover, the PQCQS membranes significantly expedited the wound healing process and inhibited scar hyperplasia better than commercial ointment (MSSG and KELO-COTE) in a rabbit ear full-thickness wounds defect model. That is, the bilayered nanofibrous membranes, with excellent antibacterial activity, hydrophilicity, hemostatic performance, scar inhibition, and wound healing properties, are appropriate candidates for wound dressings. [ABSTRACT FROM AUTHOR]

An efficient and available material for promoting skin regeneration is of great importance for public health, but it remains an elusive goal. Inspired by fetal scarless wound healing, we develop a wearable biomimetic film (WBMF) composed of hyaluronan (HA), vitamin E (VE), dopamine (DA), and β -cyclodextrin ( β -CD) that mimics the fetal context (FC) and fetal extracellular matrix (ECM) around the wound bed for dermal regeneration. First, the WBMF creates the FC of sterility, hypoxia, persistent moisture, and no secondary insults for wounds as the result of its seamless adhesion to the skin, optimum stress-stretch and high-cycle fatigue resistance matching the anisotropic tension of the skin, and water-triggered self-healing behavior. Thus, the WBMF modulates the early wound situation to minimize inflammatory response. In the meantime, the WBMF mimics the critical biological function of fetal ECM, inducing fibroblast migration, suppressing the overexpression of transforming growth factor β 1, and mediating collagen synthesis, distribution, and reestablishment. As a result, the WBMF accelerates wound healing and gains a normal dermal collagen architecture, thereby restoring scarless appearance. Overall, the WBMF provides a new paradigm for promoting skin wound healing and may find broad utility for the field of regenerative medicine.

The article offers information on a study on Blocking a1-integrin reverts the adhesive phenotype of adult fibroblasts towards a foetal-like migratory phenotype. Topics discussed include Primary foetal fibroblasts have a migratory phenotype with low gene expression of pro-adhesive molecules, reduced adhesion and improved migration; and migratory foetal phenotype changes in coatings or substrate stiffness.

Skin and skin appendages protect the body from harmful environment and prevent internal organs from dehydration. Superficial epidermal wounds usually heal without scarring, however, deep dermal wound healing commonly ends up with nonfunctioning scar formation with substantial loss of skin appendage. Wound healing is one of the most complex dynamic biological processes, during which a cascade of biomolecules combine with stem cell influx and matrix synthesis and synergistically contribute to wound healing at all levels. Although many approaches have been investigated to restore complete skin, the clinically effective therapy is still unavailable and the regeneration of perfect skin still remains a significant challenge. The complete mechanism behind scarless skin regeneration still requires further investigation. Fortunately, recent advancement in regenerative medicine empowers us more than ever to restore tissue in a regenerative manner. Many studies have elucidated and reviewed the contribution of stem cells and growth factors to scarless wound healing. This article focuses on recent advances in scarless wound healing, especially strategies to engineer pro-regenerative scaffolds to restore damaged skin in a regenerative manner., (© 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

The endometrium undergoes continuous repair and regeneration without scarring throughout the reproductive life of women. However, the mechanisms responsible for this complete restoration remain mostly unexplored. We hypothesized that the ischemic state and local hypoxia present after parturition may create a special microenvironment for endometrial healing, and that this ischemia might be caused by reduction in organ volume via postpartum uterine contraction. Here, we developed a mouse model using a combination of cesarean section and the administration of a beta 2 adrenergic receptor agonist (ritodrine hydrochloride) in postpartum mice that had been ovariectomized to exclude the effect of ovarian hormones. Our results revealed that transient hypoxia indeed occurred in postpartum uteri. Furthermore, we found that the number of M2 macrophages, which play a central role in wound healing, peaked on Postpartum Day 3 and gradually decreased thereafter in hypoxic injury sites. Almost concurrently, significant upregulation of vascular endothelial growth factor and transforming growth factor beta (TGFbeta) was observed. In particular, the antifibrotic factor TGFbeta3 was released during the endometrial healing process. These changes were significantly suppressed by inhibition of uterine contraction. Taken together, these results suggest that uterine contraction is essential, not only for hemostasis, but also for endometrial regeneration, leading to a process that involves the activation of macrophages, increased endometrial cell proliferation, and upregulation of nonfibrotic growth factors. This study paves the way to a novel approach for investigating the process of scarless wound healing., (© 2014 by the Society for the Study of Reproduction, Inc.)