Soft Tissue Regeneration Research Articles

Versatile click alginate hydrogels with protease-sensitive domains as cell responsive/instructive 3D microenvironments

Alginate (ALG) is a widely used biomaterial to create artificial extracellular matrices (ECM) for tissue engineering. Since it does not degrade in the human body, imparting proteolytic sensitivity to ALG hydrogels leverages their properties as ECM-mimics. Herein, we explored the strain-promoted azide-alkyne cycloaddition (SPAAC) as a biocompatible and bio-orthogonal click-chemistry to graft cyclooctyne-modified alginate (ALG-K) with bi-azide-functionalized PVGLIG peptides. These are sensitive to matrix metalloproteinase (MMP) and may act as crosslinkers. The ALG-K-PVGLIG conjugates (50, 125, and 250 μM PVGLIG) were characterized for peptide incorporation, crosslinking ability (double-end grafting), and enzymatic liability. For producing cell-permissive multifunctional 3D matrices for dermal fibroblast culture, oxidized ALG-K was grafted with PVGLIG and with RGD peptides for cell-adhesion. SPAAC reactions were performed immediately before cell-laden hydrogel formation by secondary ionic-crosslinking, considerably reducing the steps and time of preparation. Hydrogels with intermediate PVGLIG concentration (125 μM) presented slightly higher stiffness while promoting extensive cell spreading and higher degree of cell-cell interconnections, likely favored by cell-driven proteolytic remodeling of the network. The hydrogel-embedded cells were able to produce their own pericellular ECM, expressed MMP-2 and 14, and secreted PVGLIG-degrading enzymes. By recapitulating key ECM-like features, these hydrogels provide biologically relevant 3D matrices for soft tissue regeneration.

The Revolutionary Potential of i-PRF: A Breakthrough in Implant Dentistry

Implant dentistry has significantly advanced over the years, offering effective solutions for patients with missing teeth. However, optimizing implant success and promoting efficient osseointegration remains a continuous focus for dental professionals. Injectable Platelet-Rich Fibrin (i-PRF) has emerged as a valuable adjunctive therapy in implant dentistry, aiming to enhance the regenerative potential of tissues and improve clinical outcomes.I-PRF is an autologous blood concentrate derived from the patient's own blood, rich in platelets, leukocytes, growth factors, and fibrin matrix. This biological material offers numerous benefits in implant dentistry, including its ability to accelerate wound healing, enhance soft tissue regeneration, and stimulate bone formation. I-PRF is obtained through a simple and chairside centrifugation process, making it readily accessible and cost-effective.In conclusion, i-PRF represents a valuable adjunctive therapy in implant dentistry, providing clinicians with a natural and effective means to optimize implant success and promote tissue regeneration. As research continues to expand in this field, further investigations are needed to explore the full potential and standardize the protocols for i-PRF application, ensuring its widespread utilization and integration into routine implant procedures.

Histological and Clinical Evidence of Soft Tissue Regeneration from a Porcine Collagen Matrix - Case Report

Tooth loss results in loss of hard and soft tissue volume, making it difficult to achieve aesthetically pleasing results. In order to decrease the morbidity caused by an autologous graft in the alveolar seal, it can be replaced by a resorbable matrix of collagen. The present case report evaluated clinically and histologically a porcine collagen matrix, in soft tissue regeneration, during the installation of an implant immediately after dental extraction. After 6 months, clinically, a tissue with an optimal final aesthetic appearance was obtained and histologically, the formation of an epithelial and connective tissue compatible with that of a normal mucosa was evidenced.

The Influence of the Molecular Weight of Poly(Ethylene Oxide) on the Hydrolytic Degradation and Physical Properties of Polycaprolactone Binary Blends

The use of biodegradable polymers in tissue engineering has been widely researched due to their ability to degrade and release their components in a controlled manner, allowing for the potential regeneration of tissues. Melt blending is a common method for controlling the degradation rate of these polymers, which involves combining these materials in a molten state to create a homogenous mixture with tailored properties. In this study, polycaprolactone (PCL) was melt blended with hydrophilic poly (ethylene oxide) (PEO) of different molecular weights to assess its effect on PCL material performance. Hydrolytic degradation, thermal and viscoelastic properties, and surface hydrophilicity were performed to contrast the properties of the blends. DSC, DMA, and FTIR were performed on selected degraded PCL/PEO specimens following mass loss studies. The results showed that adding PEO to PCL reduced its melt viscosity-torque and melt temperature while increasing its hydrophilicity, optimizing PCL/PEO blend for soft tissue engineering applications and could contribute to the development of more effective and biocompatible materials for soft tissue regeneration.

Particles of Different Sizes Affect the Retention Pattern of the Fat Grafts in a Mouse Model.

Autologous fat grafting is an effective form of soft tissue regeneration. However, the optimal fat particle size and graft retention pattern need more research. The mouse inguinal fat pad was harvested and cut into fat particles of different diameters: ≥ 5 mm, 3-4 mm, 2-3 mm, 1-2 mm and 1 mm (micro-fat). A volume of0.2 ml fat was transplanted into another mouse dorsum. Volume and retention rate were measured at 1, 4, 8 and 12 weeks. Histology analysis was performed. Immunofluorescence staining was used to evaluate M1 and M2 macrophage infiltration and graft angiogenesis. Fat retention was highest in the "> 5 mm" group and lowest in the "micro-fat" group. Large vacuoles were more common in larger-diametered fat particles. There was less collagen accumulation in the well-vascularized connective tissue in the "1-2 mm" group. The infiltrated nucleated cells peak at week 4 in groups of fat particles under 3 mm and at week 8 in in groups with fat particles above 3 mm. The number of M1 macrophages peaked at week 1 and then declined in all groups except for the "5 mm" group. The number of M2 macrophages peaked at week 4 and gradually decreased through 12 weeks in the groups below 3 mm, but increased through 12 weeks in the groups above 3 mm. Vascular intensity was similar to M2 macrophage prevalence. Fat particles of different sizes may posses different retention patterns. Larger grafts have higher retention rate but worse quality. Meanwhile, smaller grafts have better quality with lower retention rate. This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Three-dimensional cultures of gingival fibroblasts on fibrin-based scaffolds for gingival augmentation: A proof-of-concept study

ObjectiveGingival tissue regeneration is associated with several challenges. Tissue engineering regenerates the different components of the tissues, providing three major elements: living cells, appropriate scaffolds, and tissue-inducing substances. This study aimed to regenerate the gingival connective tissue in vitro, using human gingival fibroblasts cultured in three-dimensional fibrin gel scaffolds. DesignHuman gingival fibroblasts were seeded in a novel three-dimensional fibrin gel scaffold and maintained in two media types: platelet lysate media (control) and collagen-stimulating media (test). Cellular viability and proliferation were assessed, and the production of collagen and other extracellular matrix components in these constructs was investigated and compared. ResultsHuman gingival fibroblasts cultured in three-dimensional cultures were metabolically active and proliferated in both media. Furthermore, histologic sections, scanning electron microscopy, and quantitative polymerase chain reaction confirmed the production of higher levels of collagen and other extracellular matrix fibers in three-dimensional constructs cultured in collagen-stimulating media. ConclusionsCulturing human gingival fibroblasts in a novel three-dimensional fibrin gel scaffold containing collagen-stimulating media resulted in a tissue-equivalent construct that mimics human gingival connective tissue. The impact of these results should be considered for further investigations, which may help to develop a compatible scaffold for gingival soft tissue regeneration and treatment of mucogingival deformities.

Biomimetic Liquid Crystal-Modified Mesoporous Silica−Based Composite Hydrogel for Soft Tissue Repair

The reconstruction of blood vessels plays a critical role in the tissue regeneration process. However, existing wound dressings in tissue engineering face challenges due to inadequate revascularization induction and a lack of vascular structure. In this study, we report the modification of mesoporous silica nanospheres (MSNs) with liquid crystal (LC) to enhance bioactivity and biocompatibility in vitro. This LC modification facilitated crucial cellular processes such as the proliferation, migration, spreading, and expression of angiogenesis−related genes and proteins in human umbilical vein endothelial cells (HUVECs). Furthermore, we incorporated LC−modified MSN within a hydrogel matrix to create a multifunctional dressing that combines the biological benefits of LC−MSN with the mechanical advantages of a hydrogel. Upon application to full−thickness wounds, these composite hydrogels exhibited accelerated healing, evidenced by enhanced granulation tissue formation, increased collagen deposition, and improved vascular development. Our findings suggest that the LC−MSN hydrogel formulation holds significant promise for the repair and regeneration of soft tissues.

Novel Bioactive Glass/Graphene Oxide-Coated Surgical Sutures for Soft Tissue Regeneration.

The combination of a commercially available PGLA (poly[glycolide-co-l-lactide]), 90:10% suture material with bioactive bioglass nanopowders (BGNs) and graphene oxide (GO)-doped BGNs offers new opportunities for the clinical application of biomaterials in soft tissue engineering. In the present experimental work, we demonstrate that GO-doped melt-derived BGNs were synthesized via the sol-gel process. After that, novel GO-doped and undoped BGNs were used to coat resorbable PGLA surgical sutures, thereby imparting bioactivity, biocompatibility, and accelerated wound healing properties to the sutures. Stable and homogeneous coatings on the surface of the sutures were achieved using an optimized vacuum sol deposition method. The phase composition, morphology, elemental characteristics, and chemical structure of uncoated and BGNs- and BGNs/GO-coated suture samples were characterized using Fourier transform infrared spectroscopy, field emission scanning electron microscopy, associated with elemental analysis, and knot performance test. In addition, in vitro bioactivity tests, biochemical tests, and in vivo tests were performed to examine the role of BGNs and GO on the biological and histopathological properties of the coated suture samples. The results indicated that the formation of BGNs and GO was enhanced significantly on the suture surface, which allowed for enhanced fibroblast attachment, migration, and proliferation and promoted the secretion of the angiogenic growth factor to speed up wound healing. These results confirmed the biocompatibility of BGNs- and BGNs/GO-coated suture samples and the positive effect of BGNs on the behavior of L929 fibroblast cells and also showed for the first time the possibility that cells can adhere and proliferate on the BGNs/GO-coated suture samples, especially in an in vivo environment. Resorbable surgical sutures with bioactive coatings, such as those prepared herein, can be an attractive biomaterial not only for hard tissue engineering but also for clinical applications in soft tissue engineering.

Highly resilient and fatigue-resistant poly(4-methyl-ε-caprolactone) porous scaffold fabricated via thiol-yne photo-crosslinking/salt-templating for soft tissue regeneration

Elastomeric scaffolds, individually customized to mimic the structural and mechanical properties of natural tissues have been used for tissue regeneration. In this regard, polyester elastic scaffolds with tunable mechanical properties and exceptional biological properties have been reported to provide mechanical support and structural integrity for tissue repair. Herein, poly(4-methyl-ε-caprolactone) (PMCL) was first double-terminated by alkynylation (PMCL-DY) as a liquid precursor at room temperature. Subsequently, three-dimensional porous scaffolds with custom shapes were fabricated from PMCL-DY via thiol-yne photocrosslinking using a practical salt template method. By manipulating the Mn of the precursor, the modulus of compression of the scaffold was easily adjusted. As evidenced by the complete recovery from 90% compression, the rapid recovery rate of >500 mm min−1, the extremely low energy loss coefficient of <0.1, and the superior fatigue resistance, the PMCL20-DY porous scaffold was confirmed to harbor excellent elastic properties. In addition, the high resilience of the scaffold was confirmed to endow it with a minimally invasive application potential. In vitro testing revealed that the 3D porous scaffold was biocompatible with rat bone marrow stromal cells (BMSCs), inducing BMSCs to differentiate into chondrogenic cells. In addition, the elastic porous scaffold demonstrated good regenerative efficiency in a 12-week rabbit cartilage defect model. Thus, the novel polyester scaffold with adaptable mechanical properties may have extensive applications in soft tissue regeneration.

A hyaluronic acid/silk fibroin/poly-dopamine-coated biomimetic hydrogel scaffold with incorporated neurotrophin-3 for spinal cord injury repair

Bio-factor stimulation is essential for axonal regeneration in the central nervous system. Thus, persistent and efficient factor delivery in the local microenvironment is an ideal strategy for spinal cord injury repair. We developed a biomimetic hydrogel scaffold to load biofactors in situ and release them in a controlled way as a promising therapeutic modality. Hyaluronic acid and silk fibroin were cross-linked as the basement of the scaffolds, and poly-dopamine coating was used to further increase the loading of factors and endow the hydrogel scaffolds with ideal physical and chemical properties and proper biocompatibility. Notably, neurotrophin-3 release from the hydrogel scaffolds was prolonged to 28 days. A spinal cord injury model was constructed for hydrogel scaffold transplantation. After eight weeks, significant NF200-positive nerve fibers were observed extending across the glial scar to the center of the injured area. Due to the release of neurotrophin-3, spinal cord regeneration was enhanced, and the cavity area of the injury graft site and inflammation associated with CD68 positive cells were reduced, which led to a significant improvement in hind limb motor function. The results show that the hyaluronic acid/silk fibroin/poly-dopamine-coated biomimetic hydrogel scaffold achieved locally slow release of neurotrophin-3, thus facilitating the regeneration of injured spinal cord. Statement of significanceHydrogels have received great attention in spinal cord regeneration. Current research has focused on more efficient and controlled release of bio-factors. Here, we adopted a mussel-inspired strategy to functionalize the hyaluronic acid/silk fibroin hydrogel scaffold to increase the load of neurotrophin-3 and extend the release time. The hydrogel scaffolds have ideal physiochemical properties, proper release rate, and biocompatibility. Owing to the continuous neurotrophin-3 release from implanted scaffolds, cavity formation is reduced, inflammation alleviated, and spinal cord regeneration enhanced, indicating great potential for bio-factor delivery in soft tissue regeneration applications.

Collagen-mesenchymal stem cell spheroids in suspension promote high adipogenic capacity

Human mesenchymal stem cells (hMSC) represent a unique and promising platform because of their ability to promote soft tissue regeneration, particularly their ability to differentiate into adipocytes, which are important for adipose tissue regeneration. In this context, type I collagen is the most abundant extracellular matrix component of adipose tissue and can act as a natural spheroid source to support the differentiation process of stem cells. However, spheroids based on collagen and hMSCs without numerous pro-adipogenic factors that can induce adipogenesis have not yet been investigated. In this study, we focused on developing collagen-hMSC spheroids capable of differentiating into adipocyte-like cells in a short time (eight culture days) without adipogenic factors, with potential applications in adipose tissue repair. The physical and chemical properties of the spheroids indicated successful cross-linking of collagen. Upon spheroid development, stability, cell viability, and metabolic activity of the constructs were maintained. During adipogenesis, cell morphology shows significant changes, in which cells change from a fibroblast-like shape to an adipocyte-like shape, and adipogenic gene expression after eight days of cell culture. These results support the utility of collagen-hMSC 3 mg ml−1 collagen concentration spheroids to differentiate into adipocyte-like cells in a short time without adverse effects on biocompatibility, metabolic activity, or cell morphology, suggesting that this construct may be used in soft tissue engineering.

A Critical Review on Classified Excipient Sodium-Alginate-Based Hydrogels: Modification, Characterization, and Application in Soft Tissue Engineering.

Alginates are polysaccharides that are produced naturally and can be isolated from brown sea algae and bacteria. Sodium alginate (SA) is utilized extensively in the field of biological soft tissue repair and regeneration owing to its low cost, high biological compatibility, and quick and moderate crosslinking. In addition to their high printability, SA hydrogels have found growing popularity in tissue engineering, particularly due to the advent of 3D bioprinting. There is a developing curiosity in tissue engineering with SA-based composite hydrogels and their potential for further improvement in terms of material modification, the molding process, and their application. This has resulted in numerous productive outcomes. The use of 3D scaffolds for growing cells and tissues in tissue engineering and 3D cell culture is an innovative technique for developing in vitro culture models that mimic the in vivo environment. Especially compared to in vivo models, in vitro models were more ethical and cost-effective, and they stimulate tissue growth. This article discusses the use of sodium alginate (SA) in tissue engineering, focusing on SA modification techniques and providing a comparative examination of the properties of several SA-based hydrogels. This review also covers hydrogel preparation techniques, and a catalogue of patents covering different hydrogel formulations is also discussed. Finally, SA-based hydrogel applications and future research areas concerning SA-based hydrogels in tissue engineering were examined.

Nanoscale borosilicate bioactive glass for regenerative therapy of full-thickness skin defects in rabbit animal model.

Bioactive glass (BG) occupies a significant position in the field of hard and soft tissue regeneration. Different processing techniques and formulas have been introduced to expand their regenerative, angiogenic, and antibacterial properties. In the present study, a new formula of bborosilicate bioactive glass nanofibers was prepared and tested for its wound-healing efficacy in a rabbit animal model. The glass formula ((1-2) mol% of B2O3 (68-69) mol% of SiO2, and (29-30) mol% of CaO) was prepared primarily by the sol-gel technique followed by the electrospinning technique. The material was characterized for its ultrastructure using scanning electron microscopy, chemical composition using FTIR, and its dynamic in vitro biodegradability using ICP-AES. Twelve rabbits were subjected to surgical induction of full-thickness skin defects using a 1cm2 custom-made stainlessteel skin punch. The bioactive glass nanofibers were used as a grafting material in 6 experimental rabbits, while the defects in the remaining rabbits were considered as the negative control samples. All defects were assessed clinically for the decrease in wound size and clinical signs of healing and histologically for angiogenesis, collagen density, inflammatory response, cell recruitment, epithelial lining, and appendages at 1,2 and 3weeks following the intervention. Structural analysis of the glass fibers confirmed their nano-size which ranged from 150 to 700nm. Moreover, the chemical analysis confirmed the presence of SiO2 and B2O3 groups within the structure of the nanofibers. Additionally, dynamic biodegradation analysis confirmed the rapid degradation of the material starting from the first 24h and rapid leaching of calcium, silicon, and boron ions confirming its bioactivity. The wound healing study of the nanofibrous scaffold confirmed its ability to accelerate wound healing and the closure rate in healthy rabbits. Histological analysis of the defects confirmed the angiogenic, regenerative and antibacterial ability of the material throughout the study period. The results unveil the powerful therapeutic properties of the formed nanofibers and open a new gate for more experimental and clinical applications.

Stem-cell based soft tissue substitutes: Engineering of crosslinked polylysine-hyaluronic acid microspheres ladened with gingival mesenchymal stem cells for collagen tissue regeneration and angiogenesis.

The aim of this study was to construct crosslinked polylysine-hyaluronic acid microspheres (pl-HAM) ladened with gingival mesenchymal stem cells (GMSCs) and explore its biologic behavior in soft tissue regeneration. The effects of the crosslinked pl-HAM on the biocompatibility and the recruitment of L-929 cells and GMSCs were detected in vitro. Moreover, the regeneration of subcutaneous collagen tissue, angiogenesis and the endogenous stem cells recruitment were investigated in vivo. We also detected the cell developing capability of pl-HAMs. The crosslinked pl-HAMs appeared to be completely spherical-shaped particles and had good biocompatibility. L-929 cells and GMSCs grew around the pl-HAMs and increased gradually. Cell migration experiments showed that pl-HAMs combined with GMSCs could promote the migration of vascular endothelial cells significantly. Meanwhile, the green fluorescent protein-GMSCs in the pl-HAM group still remain in the soft tissue regeneration area 2weeks after surgery. The results of in vivo studies showed that denser collagen deposition and more angiogenesis-related indicator CD31 expression in the pl-HAMs+ GMSCs + GeL group compared with the pl-HAMs + GeL group. Immunofluorescence showed that CD44, CD90, CD73 co-staining positive cells surrounded the microspheres in both pl-HAMs + GeL group and pl-HAM + GMSCs + GeL group. The crosslinked pl-HAM ladened with GMSCs system could provide a suitable microenvironment for collagen tissue regeneration, angiogenesis and endogenous stem cells recruitment, which may be an alternative to autogenous soft tissue grafts for minimally invasive treatments for periodontal soft tissue defects in the future.

Facile synthesis of electrospun antibacterial bioactive glass based micronanofibre (ABGmnf) for exalted wound healing: In vitro and in vivo studies

Recently, bioactive glass has shown an incredible potential to address the assortment of chronic wounds including diabetic and venous ulcers. In this regard, the textural properties of bioactive glass (BG)-based micronanofibre, which are analogous to the fibrin clot that aggregates platelets, provide advantages that support the coagulation cascade and subsequent soft tissue regeneration by providing mechanical support and a source of various therapeutic ions. In this correspondence, we synthesized a binary composition comprising (70-x) mol% SiO2, (30-y) mol% CaO, 1 < x < 5 mol% B2O3 and 0.001< y < 0.1mol% Ag2O composition (ABGmnf) via sol-gel method followed by fabrication of the electrospun fibres, and state-of-art characterizations, XRD, FTIR, and FESEM-EDXalong with biological studies including in-vitro cytocompatibility, 2D wound healing, antibacterial activities by determination of minimum inhibitory concentration (MIC). In addition, the concentration of proinflammatory cytokines (TNF-α and IL-6) and various hematological, biochemical, and histopathological parameters were used to establish the in vivo biocompatibility. The in vivo wound healing assay, which demonstrated rapid wound closure, was then examined. ABGmnf's excellent cyto- and biocompatibility could be demonstrated by the above findings alongwith the lack of host-material interaction, as well.

Toughening Double Network Hydrogels by Polyelectrolytes.

Hoffmeister effect of inorganic salts has been verified as a promising way to toughen hydrogels, however, the high concentration of inorganic salts may accompany by poor biocompatibility. In this work, for the first time, we find that polyelectrolytes can obviously elevate the mechanical performances of hydrogels through Hoffmeister effect. The introduction of anionic poly(sodium acrylate) (P(iAA)) into poly(vinyl alcohol) (PVA) hydrogel induces the aggregation and crystallization of PVA to boost the mechanical properties of the resulting double network hydrogel: elevation of 73, 64, 28, 135, and 19 times in the tensile strength, compressive strength, Young's modulus, toughness, and fracture energy compared with poly(acrylic acid) (PAA), respectively. It is noteworthy that the mechanical performances of the hydrogels can be flexibly tuned by the variation of polyelectrolyte concentration, ionization degree, relative hydrophobicity of the ionic component and polyelectrolyte type in a wide range. This strategy is verified to work for other Hoffmeister effect-sensitive polymers and polyelectrolytes. Also, the introduction of urea bonds into polyelectrolytes can further improve the mechanical properties and anti-swelling capability of hydrogels. As a biomedical patch, the advanced hydrogel can efficiently inhibit hernia formation and promote the regeneration of soft tissues in abdominal wall defect model. This article is protected by copyright. All rights reserved.

Construction of a Localized and Long-Acting CCN2 Delivery System on Percutaneous Ti Implant Surfaces for Enhanced Soft-Tissue Integration

Soft-tissue integration (STI) plays an essential role in the long-term success of percutaneous Ti implants since it acts as a biological barrier that protects the soft and hard tissue around implants. Surface modification of Ti implants with drug-release properties to achieve soft-tissue regeneration has been proven to be effective in STI. However, the short-acting effect caused by the uncontrolled drug release of the topical delivery system limits long-term STI enhancement. Herein, a long-acting protein delivery system for Ti implants that involved micro-arc oxidation of Ti surfaces (MAO-Ti) and localized immobilization of cellular communication network factor 2 (CCN2) bearing mesoporous silica nanoparticles (MSNs) on MAO-Ti was prepared, namely, CCN2@MSNs-Ti. The CCN2 release study of CCN2@MSNs-Ti demonstrated a sustained-release profile for 21 days, which was able to maintain long-term stable STI. In addition, in vitro cell behavior evaluation results indicated that CCN2@MSNs-Ti could promote the STI-related biological response of human dermal fibroblasts via the FAK-MAPK pathway. More importantly, the system could effectively enhance STI after 4 weeks and proinflammatory factors in the soft tissue decreased significantly in a rat model of implantation. These results denote that CCN2@MSNs-Ti showed an appealing application prospect for enhanced STI around transcutaneous Ti implants, which would ultimately result in an increased success rate of percutaneous Ti implants.

Introduction to ECM Advances in Chinese Dermatologic Surgery.

We are pleased to present the Dermatologic Surgery Special Issue, which is focused on the extracellular matrix (ECM) in skin regeneration and dermopathy treatment. Regenerative medicine based on ECM is one of the most promising tools for skin rejuvenation and soft tissue regeneration. In addition, the occurrence of dermopathy is highly related to the disturbance of the ECM. In this issue, we provide the most recent advances in determining the role of the ECM in research and clinical application. This issue presents several articles on the cutting edge of dermatologic surgery. Dermatofibrosarcoma protuberans (DFSP) was discovered to have fibroblastic activity, and a variety of neural features were discovered, which validated DFSP’s fibroblastic origin and tendency toward neural differentiation. The efficacy and safety of picosecond laser therapy (PLT) was proven in the treatment of melasma. In addition, the efficacy and safety assessment found that the ECM is a dressing that promotes wound healing after PLT, which can shorten the downtime by alleviating erythema and edema and proceeding with scab shedding related to PLT. The treatment of keloids, a disease caused by ECM disorder, is an urgent problem in clinical practice. In this special issue, different keloid treatments are presented, including punch excision combined with drug injection, autologous split-thickness skin graft and postoperative radiotherapy, surgical excision with electron beam radiotherapy, and reduced incision tension of keloid surgery by tightening the fascia layer. The illumination of these promising strategies will be conducive to the development of future targeted therapies. Finally, we are fortunate to have several peer-reviewed literatures on the applications of ECM in skin regeneration medicine. Pingping Lin et al elucidated the dynamic composition and potential roles of the extracellular matrix in normal skin, the wound healing process, and abnormal skin scarring. Yixin Wang et al provided an overview of the clinical research, limitations, and potential application of botulinum toxin type A in the prevention and treatment of traumatic or postoperative scars. Weiyuan Zhang et al investigated the mechanism of Mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) in reducing inflammation, promoting angiogenesis, promoting the proliferation and migration of epithelial cells and fibroblasts, and ECM remodeling during wound healing.

Prevention of Postoperative Bleeding in Anticoagulated Patients Undergoing Oral Surgery: Use of Platelet Rich Plasma

Introduction: Anticoagulant therapy is essential for patients with various medical conditions. The use of anticoagulant medications is associated with a prolonged bleeding time. Platelet-rich plasma (PRP) contains a high concentration of platelets. PRP has been used to improve bone and soft tissue regeneration and lessen postoperative complications. Study design: It is a randomized controlled study conducted at DOW International Dental College, Karachi for the duration of six months from August 2022 to January 2023. Material and Methods: The study was done on 40 patients who visited tertiary care unit for duration of six months. There were 6 patients that belonged to the age group 40-50 years. 19 and 15 patients were in the age group 55-60 years and 60-65 years respectively. There were 14 males and 26 females included in our study. There were 72 extractions performed on these patients. Results: It was found that there were 4 patients who reported about hemorrhagic complications. There were two women that had hemorrhage linked to poor placement of platelet gel. One patient reported about hemorrhage related to severe formation of coagulum. Mild bleeding was observed in 13 patients. Conclusion: In conclusion the results of our trial suggest that PRP is a successful anticoagulant therapy that can be used for preventing any post-operative hemorrhagic complication among patients going through dental surgery, as PRP is easy to use, it has low cost and a good placement into residual alveolar bone, therefore it has better outcomes among patients. Keywords: postoperative bleeding, anticoagulant therapy and Platelet-rich plasma.

Evaluation of the effect of 3D-bioprinted gingival fibroblast-encapsulated ADM scaffolds on keratinized gingival augmentation.

The keratinized gingiva plays an important role in maintaining healthy periodontal and peri-implant tissue. Acellular dermal matrix (ADM), as a substitute biomaterial, has a porous structure and good biocompatibility. 3D-bioprinting has the potential for tissue engineering because it enables precise loading of cells layer-by-layer. Herein, we bioprinted ADM scaffold encapsulating gingival fibroblasts (GFs) and evaluated its efficacy in keratinized gingiva augmentation in vivo to assess its potential for clinical periodontal tissue regeneration. GFs were extracted from the gingiva of beagles and transfected with a green fluorescent protein (GFP). The ADM scaffold (ADM cell-free group) was constructed using ADM, gelatin, and sodium alginate mixed at an appropriate ratio via 3D-bioprinting. The ADM cell scaffold (ADM cell group) was established by adding extra GFs in the same manner. Six beagles were divided into blank control, ADM cell-free, and ADM cell groups; and implant surgery was performed. The keratinized gingiva was clinically and histologically evaluated at baseline and after 2 months. GFs transfected with GFPs expressed green fluorescence and were present in new tissue in the ADM cell group and not observed in the ADM cell-free group. At 2 months after surgery, the keratinized gingival augmentation in the ADM cell group was significantly more than that in the ADM cell-free group. Attached gingival augmentation was also observed more in the ADM cell group than that in the ADM cell-free group. Histological staining showed that the tissue in the ADM cell group displayed a more integrated structure and higher expression of COL I, COL III, and VEGF-A than those in the ADM cell-free group. 3D-bioprinted GF-encapsulated ADM scaffolds increased the amount of keratinized gingiva in vivo, suggesting that 3D-bioprinting has great potential for oral soft tissue regeneration.