Acellular Dermal Matrix Scaffold Research Articles

Using a Xenogeneic Acellular Dermal Matrix Membrane to Enhance the Reparability of Bone Marrow Mesenchymal Stem Cells for Cartilage Injury.

Due to its avascular organization and low mitotic ability, articular cartilage possesses limited intrinsic regenerative capabilities. The aim of this study is to achieve one-step cartilage repair in situ via combining bone marrow stem cells (BMSCs) with a xenogeneic Acellular dermal matrix (ADM) membrane. The ADM membranes were harvested from Sprague-Dawley (SD) rats through standard decellularization procedures. The characterization of the scaffolds was measured, including the morphology and physical properties of the ADM membrane. The in vitro experiments included the cell distribution, chondrogenic matrix quantification, and viability evaluation of the scaffolds. Adult male New Zealand white rabbits were used for the in vivo evaluation. Isolated microfracture was performed in the control (MF group) in the left knee and the tested ADM group was included as an experimental group when an ADM scaffold was implanted through matching with the defect after microfracture in the right knee. At 6, 12, and 24 weeks post-surgery, the rabbits were sacrificed for further research. The ADM could adsorb water and had excellent porosity. The bone marrow stem cells (BMSCs) grew well when seeded on the ADM scaffold, demonstrating a characteristic spindle-shaped morphology. The ADM group exhibited an excellent proliferative capacity as well as the cartilaginous matrix and collagen production of the BMSCs. In the rabbit model, the ADM group showed earlier filling, more hyaline-like neo-tissue formation, and better interfacial integration between the defects and normal cartilage compared with the microfracture (MF) group at 6, 12, and 24 weeks post-surgery. In addition, neither intra-articular inflammation nor a rejection reaction was observed after the implantation of the ADM scaffold. This study provides a promising biomaterial-based strategy for cartilage repair and is worth further investigation in large animal models.

Converting Acellular Dermal Matrix into On-Demand Versatile Skin Scaffolds by a Balanceable Crosslinking Approach for Integrated Infected Wounds Therapy.

Ideal tissue-engineered skin scaffolds should possess integrated therapeutic effects and multifunctionality, such as broad-spectrum antibacterial properties, adjustable mechanical properties, and bionic structure. Acellular dermal matrix (ADM) has been broadly used in many surgical applications as an alternative treatment to the "gold standard" tissue transplantation. However, insufficient broad-spectrum antibacterial and mechanical properties for therapeutic efficacy limit the practical clinical applications of ADM. Herein, a balanceable crosslinking approach based on oxidized 2-hydroxypropyltrimethyl ammonium chloride chitosan (OHTCC) was developed for converting ADM into on-demand versatile skin scaffolds for integrated infected wounds therapy. Comprehensive experiments show that different oxidation degrees of OHTCC have significative influences on the specific origins of OHTCC-crosslinked ADM scaffolds (OHTCC-ADM). OHTCC with an oxidation degree of about 13% could prosperously balance the physiochemical properties, antibacterial functionality, and cytocompatibility of the OHTCC-ADM scaffolds. Owing to the natural features and comprehensive crosslinking effects, the proposed OHTCC-ADM scaffolds possessed the desirable multifunctional properties, including adjustable mechanical, degradable characteristics, and thermal stability. In vitro/in vivo biostudies indicated that OHTCC-ADM scaffolds own well-pleasing broad-spectrum antibacterial performances and play effectively therapeutic roles in treating infection, inhibiting inflammation, promoting angiogenesis, and promoting collagen deposition to enhance the infected wound healing. This study proposes a facile balanceable crosslinking approach for the design of ADM-based versatile skin scaffolds for integrated infected wounds therapy.

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.

Histologic characterization of orbicularis oris muscle with anew acellular dermal matrix grafts in a rabbit model.

Muscular dysplasia is the key factor in influencing surgical outcomes in patients with cleft lip/palate. In this research, we attempted to evaluate a new acellular dermal matrix (ADM) as a substitute for reconstruction of the orbicularis oris muscle with growth factors such as Insulin-Like Growth Factor I (IGF-I), vascular endothelial growth factor (VEGF) in a rabbit model. 30 male New Zealand Rabbits (2-3m, 1700-2000g) were divided into four groups as follows; a group in which the orbicularis oris muscle of the upper lip was implanted with ADM, a group in which the orbicularis oris muscle of the upper lip was implanted with ADM+IGF-I+VEGF, a group in which the upper lip was operated without implantation of an ADM scaffold, and a normal upper lip for comparison. Macroscopic observation, histological evaluation, and immunohistochemistry were employed to evaluate levels of the muscle regeneration, vascularization, and inflammation at 1, 2, 4, 6, and 12weeks after the operation. All wounds healed well without infection, immune rejection and so on. Histological evaluation showed that ADM was totally degraded and replaced by connective tissue. The area in which the ADM scaffold was coated with growth factors show a significant increase in the formation of new myofibers after injury, and the vascularization improved compared to the control group and the normal group. In regard to the degrees of inflammation, there were no notable differences among the groups. In conclusion, Our study indicated that ADM grafts combined with IGF-I and VEGF have potential advantages in alleviating muscular dysplasia in cleft lip treatment.

Oxidized cyclodextrin inclusion tea tree oil to prepare long‐lasting antibacterial collagen scaffold for enhanced wound healing

AbstractNot only are the physicochemical properties and biocompatibility of biomaterials important considerations, but also their antibacterial properties. Fetal cowhide acellular dermal matrix (FADM), as a collagen scaffold with good biocompatibility and bioactivity, is difficult to be used to promote wound healing due to lack of sufficient mechanical strength and resistance to degradation. In order to solve this defect and give it long‐lasting antibacterial properties, a novel chemically‐cross‐linked antibacterial fetal cowhide acellular dermal matrix scaffold (β‐CD/TTO‐FADM) was fabricated by simultaneous modification by oxidized cyclodextrin (OCD) and tea tree oil (TTO). The cross‐linking of OCD improved the physical and chemical properties of FADM. TTO endowed it wide‐spectrum antibacterial activity against Escherichia coli and Staphylococcus aureus. Apart from this, the drug‐carrying capacity of OCD could also control the release of the TTO, and made the antibacterial ability durable and temperature sensitive. In addition, cell experiments and animal experiments showed that β‐CD/TTO‐FADM had good biocompatibility and could accelerate the wound healing process. Overall, an improved wound dressing with antibacterial properties that can be used in clinics has been developed, and it has also provided ideas for the development and application of drug‐loaded crosslinking agents.

Biological evaluations of decellularized extracellular matrix collagen microparticles prepared based on plant enzymes and aqueous two-phase method.

For patients with extensive full-thickness burns who do not have sufficient autologous split-thickness skin for skin grafts, the application of biological skin substitutes may be considered. The aim of this study was to find an optimal new type method for the production of a biovital skin substitute based on acellular dermal matrix (ADM) and preclinical evaluations. In this work, 25 methods of ADM production were assessed. The proposed methods are based on the use of the following enzymes: papain, Carica papaya lipase (CPL), and purification using a polymer/salt aqueous two-phase system. The obtained ADM samples were characterized via scanning electron microscopy (SEM), porosity measurement and water vapor transmission test. Results showed that the collagen bundles of ADM microparticles were intact and orderly. Through differential scanning calorimetry (DSC), thermo gravimetric analysis (TGA) and biocompatibility tests, the results indicated that the proportion of papain and CPL was the same and 5 h processing time are the optimum conditions for ADM preparation and the material showed good biocompatibility. Our results suggested that the potential of developing this kind of decellularization process to manufacture ADM scaffolds for clinical application.

Biological Evaluation of Acellular Cartilaginous and Dermal Matrixes as Tissue Engineering Scaffolds for Cartilage Regeneration.

An acellular matrix (AM) as a kind of natural biomaterial is gaining increasing attention in tissue engineering applications. An acellular cartilaginous matrix (ACM) and acellular dermal matrix (ADM) are two kinds of the most widely used AMs in cartilage tissue engineering. However, there is still debate over which of these AMs achieves optimal cartilage regeneration, especially in immunocompetent large animals. In the current study, we fabricated porous ADM and ACM scaffolds by a freeze-drying method and confirmed that ADM had a larger pore size than ACM. By recolonization with goat auricular chondrocytes and in vitro culture, ADM scaffolds exhibited a higher cell adhesion rate, more homogeneous chondrocyte distribution, and neocartilage formation compared with ACM. Additionally, quantitative polymerase chain reaction (qPCR) indicated that expression of cartilage-related genes, including ACAN, COLIIA1, and SOX9, was significantly higher in the ADM group than the ACM group. Furthermore, after subcutaneous implantation in a goat, histological evaluation showed that ADM achieved more stable and matured cartilage compared with ACM, which was confirmed by quantitative data including the wet weight, volume, and contents of DNA, GAG, total collagen, and collagen II. Additionally, immunological assessment suggested that ADM evoked a low immune response compared with ACM as evidenced by qPCR and immunohistochemical analyses of CD3 and CD68, and TUNEL. Collectively, our results indicate that ADM is a more suitable AM for cartilage regeneration, which can be used for cartilage regeneration in immunocompetent large animals.

Influence of porcine urinary bladder matrix and porcine acellular dermal matrix on wound healing of full-thickness skin defect in diabetic mice

Influence of porcine urinary bladder matrix and porcine acellular dermal matrix on wound healing of full-thickness skin defect in diabetic mice

Optimal Bioprinting Parameters and Experimental Investigation of Acellular Dermal Matrix Scaffold

Acellular dermal matrix (ADM) as a biomaterial is currently believed to be promising tissue repair improvement. With the development of tissue engineering, ADM is increasingly used as biological scaffolds. We explored the feasibility and performance of ADM biological scaffolds that fabricated by 3D printing. This paper presented our study on the printability of 3D printed ADM scaffolds, with a focus on identifying the influence of printing parameters/conditions on printability. To characterize the printability, we examined the fiber morphology, pore size, strand diameter, and mechanical property of the printed scaffolds. Our results revealed that the printability could be affected by a number of factors and among them, the most considerable one was related to the nozzle diameter and the composition of ADM. We then evaluated the biocompatibility in terms of cytotoxicity, cell proliferation and vivisection. In vitro evaluation of the ADM scaffolds was carried out and the experimental results indicated that cells were viable and proliferative during the period of study. In vivo results also indicated that the defect area was well repaired without any noticeable infection, hematoma and other conditions. In conclusion, ADM could be reconstructed with 3D printing technology and ADM biological scaffold has potential applications for tissue engineering.

Application of Amniotic Stem Cells on an Acellular Dermal Matrix Scaffold in a Burned Patient: A Case Report

BackgroundAdvances in science have allowed newly created medicinal products based on gene therapy, somatic cell therapy, and tissue engineering to be used in the treatment of human diseases. December 2008 legislation aims to ensure they are both safe for patients and available throughout the European Union. Amniotic stem cells are designated by the European Medicines Agency Committee for Advanced Therapies as an advanced therapy medicinal product; therefore, production must be in accordance with Regulation (EC) No. 1394/2007 of the European Council of 13 November 2007 on advanced therapy medicinal products. ObjectivesThis article details preliminary results of innovative amniotic stem cell transplant (supported by an acellular dermal matrix [ADM] produced in-house with Suprathel wound and burn dressing) in a burn patient and compares them with results in a patient treated with allogeneic skin. Material and MethodsAmniotic stem cells were applied to a 40-year-old patient with IIb°/III° thermal burns of 36% of total body surface area and III°/IV° of 1%. Wound healing was assessed by histologic examination and the Bates-Jensen scale. Reduction in pain perception was verified by 10-point visual analog scale. Hospitalization time was compared to length of stay for patients treated with standard therapy. ResultsThe patient was discharged from hospital on the 12th day after surgery with complete wound healing (almost 2 times shorter than the control). ConclusionsThe use of amniotic stem cells and ADM may be the optimal method for burn treatment.

Exploration of Robotic Direct to Implant Breast Reconstruction.

Breast reconstruction has undergone significant innovation over the past 50 years. Both the development of nipple sparing mastectomy and the use of acellular dermal matrices have facilitated the concept of direct to implant (DTI) reconstruction. The next step in this evolution is further limiting the length of incisions as well as placing access in a more remote location. A robot-assisted surgical approach for DTI reconstruction (R-DTI) with an acellular dermal matrix scaffold is feasible and addresses limitations with open approaches and ergonomics. The authors performed a cadaveric exploration to demonstrate proof of concept and feasibility for an R-DTI following a robot-assisted nipple sparing mastectomy. Tremor stabilization, direct visualization, endo-wristed robotic instrumentation, and exposure were noted as key benefits over existing open DTI reconstruction techniques. Additionally, the ability to have a more remote access to entry at the perimeter of the breast eliminated incisional tension which can jeopardize reconstructive results. Further exploration and procedure refinements are warranted.

Characterization of different biodegradable scaffolds in tissue engineering.

The aim of the present study was to compare the characteristics of acellular dermal matrix (ADM), small intestinal submucosa (SIS) and Bio-Gide scaffolds with acellular vascular matrix (ACVM)-0.25% human-like collagen I (HLC-I) scaffold in tissue engineering blood vessels. The ACVM-0.25% HLC-I scaffold was prepared and compared with ADM, SIS and Bio-Gide scaffolds via hematoxylin and eosin (H&E) staining, Masson staining and scanning electron microscope (SEM) observations. Primary human gingival fibroblasts (HGFs) were cultured and identified. Then, the experiment was established via the seeding of HGFs on different scaffolds for 1, 4 and 7 days. The compatibility of four different scaffolds with HGFs was evaluated by H&E staining, SEM observation and Cell Counting Kit-8 assay. Then, a series of experiments were conducted to evaluate water absorption capacities, mechanical abilities, the ultra-microstructure and the cytotoxicity of the four scaffolds. The ACVM-0.25% HLC-I scaffold was revealed to exhibit the best cell proliferation and good cell architecture. ADM and Bio-Gide scaffolds exhibited good mechanical stability but cell proliferation was reduced when compared with the ACVM-0.25% HLC-I scaffold. In addition, SIS scaffolds exhibited the worst cell proliferation. The ACVM-0.25% HLC-I scaffold exhibited the best water absorption, followed by the SIS and Bio-Gide scaffolds, and then the ADM scaffold. In conclusion, the ACVM-0.25% HLC-I scaffold has good mechanical properties as a tissue engineering scaffold and the present results suggest that it has better biological characterization when compared with other scaffold types.

ADM Scaffolds Generate a Pro-regenerative Microenvironment During Full-Thickness Cutaneous Wound Healing Through M2 Macrophage Polarization via Lamtor1.

Adult mammalian skin has a defective regenerative capacity following full-thickness cutaneous injury; this defect overshadows the complete physiological functions of the skin. Immune-mediated skin reconstruction driven by biological scaffolds is a recently developed innovative repair strategy to support regenerative wound healing. However, to date, little is known about how biological scaffolds orchestrate the immune response to promote regeneration. Here, using acellular dermal matrix (ADM) scaffolds, we discovered that the default pro-inflammatory response was altered in response to a pro-regenerative response characterized by specific M2 polarization. M2 macrophages subsequently produced a series of wound healing factors, including matrix metalloproteinases (Mmps), and growth factors which promoted cell proliferation, stabilized angiogenesis, and remodeled the extracellular matrix. Our investigations further revealed that the M2 polarization of macrophages arose from an ADM scaffold-derived amino acid sufficiency signal by collagen degradation via macrophage phagocytosis, which activated the acid-sensing pathway (v-ATPase, Lamtor1, and mTORC1). Lamtor1, the acid-sensing pathway-associated lysosomal adaptor protein was critical for inducing M2 polarization, while with the presence of extracellular interleukin 4 (IL4). Our results suggest that ADM scaffolds generate a pro-regenerative microenvironment during full-thickness cutaneous wound healing through M2 macrophage polarization via Lamtor1.

Dynamic multiphoton imaging of acellular dermal matrix scaffolds seeded with mesenchymal stem cells in diabetic wound healing.

Significantly effective therapies need to be developed for chronic nonhealing diabetic wounds. In this work, the topical transplantation of mesenchymal stem cell (MSC) seeded on an acellular dermal matrix (ADM) scaffold is proposed as a novel therapeutic strategy for diabetic cutaneous wound healing. GFP-labeled MSCs were cocultured with an ADM scaffold that was decellularized from normal mouse skin. These cultures were subsequently transplanted as a whole into the full-thickness cutaneous wound site in streptozotocin-induced diabetic mice. Wounds treated with MSC-ADM demonstrated an increased percentage of wound closure. The treatment of MSC-ADM also greatly increased angiogenesis and rapidly completed the reepithelialization of newly formed skin on diabetic mice. More importantly, multiphoton microscopy was used for the intravital and dynamic monitoring of collagen type I (Col-I) fibers synthesis via second harmonic generation imaging. The synthesis of Col-I fibers during diabetic wound healing is of great significance for revealing wound repair mechanisms. In addition, the activity of GFP-labeled MSCs during wound healing was simultaneously traced via two-photon excitation fluorescence imaging. Our research offers a novel advanced nonlinear optical imaging method for monitoring the diabetic wound healing process while the ADM and MSCs interact in situ. Schematic of dynamic imaging of ADM scaffolds seeded with mesenchymal stem cells in diabetic wound healing using multiphoton microscopy. PMT, photo-multiplier tube.

Acellular dermal matrix scaffolds coated with connective tissue growth factor accelerate diabetic wound healing by increasing fibronectin through PKC signalling pathway.

The regional injection of connective tissue growth factor (CTGF) for diabetic wound healing requires multiple components and results in a substantial loss of its biological activity. Acellular dermal matrix (ADM) scaffolds are optimal candidates for delivering these factors to local ischaemic environments. In this study, we explored whether CTGF loaded on ADM scaffolds can enhance fibronectin (FN) expression to accelerate diabetic wound healing via the protein kinase C (PKC) signalling pathway. The performance of CTGF and CTGF+PKC inhibitor, which were loaded on ADM scaffolds to treat dorsal skin wounds in streptozotocin-induced diabetic mice, was evaluated with naked ADM as a control. Wound closure showed that ADM scaffolds loaded with CTGF induced greater diabetic wound healing in the early stage of the wound in diabetic mice. Moreover, ADM scaffolds loaded with CTGF obviously increased the expression of FN both at the mRNA and protein levels, whereas the expression of FN was significantly reduced in the inhibitor group. Furthermore, the ADM+CTGF group, which produce FN, obviously promoted alpha-smooth muscle actin and transforming growth factor-beta expression and enhanced neovasculature and collagen synthesis at the wound sites. ADM scaffolds loaded with CTGF+PKC inhibitor delayed diabetic wound healing, indicating that FN expression was mediated by the PKC signalling pathway. Our findings offer new perspectives for the treatment of diabetic wound healing and suggest a rationale for the clinical evaluation of CTGF use in diabetic wound healing.

CXCR4 antagonist delivery on decellularized skin scaffold facilitates impaired wound healing in diabetic mice by increasing expression of SDF-1 and enhancing migration of CXCR4-positive cells.

C-X-C chemokine receptor type 4 (CXCR4) is an alpha-chemokine receptor specific for stromal cell-derived factor 1 (SDF-1 also called CXCL12). The antagonist of CXCR4 can mobilize CD34+ cells and hematopoietic stem cells from bone marrow within several hours, and it has an efficacy on diabetes ulcer through acting on the SDF-1/CXCR4 axis. In this study, we investigated for the first time whether the antagonist of CXCR4 (Plerixafor/AMD3100) delivered on acellular dermal matrix (ADM) may accelerate diabetes-impaired wound healing. ADM scaffolds were fabricated from nondiabetic mouse skin through decellularization processing and incorporated with AMD3100 to construct ADM-AMD3100 scaffold. Full-thickness cutaneous wound in streptozotocin (STZ)-induced diabetic mice were treated with ADM, AMD3100, or ADM-AMD3100. 21 days after treatment, wound closure in ADM-AMD3100-treated mice was more complete than ADM group and AMD3100 group, and it was accompanied by thicker collagen formation. Correspondingly, diabetic mice treated with ADM-AMD3100 demonstrated prominent neovascularization (higher capillary density and vascular smooth muscle actin), which were accompanied by up-regulated mRNA levels of SDF-1 and enhanced migration of CXCR4 in the granulation tissue. Our results demonstrate that ADM scaffold provide perfect niche for loading AMD3100 and ADM-AMD3100 is a promising method for diabetic wound healing mainly by increasing expression of SDF-1 and enhancing migration of CXCR4-positive cells.

Activities of MSCs Derived from Transgenic Mice Seeded on ADM Scaffolds in Wound Healing and Assessment by Advanced Optical Techniques

Background/Aims: Bone marrow Mesenchymal stem cells (MSCs) are promising for promoting cutaneous wound healing through reinforcing cellular processes. We evaluated the effect of GFP-tagged MSCs transplantation on skin regeneration in excisional wounds in mice. Methods: MSCs from GFP-labeled transgenic mice were co-cultured with acellular dermal matrix (ADM) scaffolds, and MSC-ADM scaffolds were transplanted into surgical skin wounds of BALB/c mice. After implantation, the survival and behavior of MSCs were examined by second harmonic generation and two-photon excitation fluorescence imaging, western blotting and DNA amplification and sequencing. Results: GFP-tagged MSCs were retained inside the regenerating skin until day 14 post-transplantation. Alpha-smooth muscle actin (α-SMA) and vimentin (VIM) were detected at 3, 5, 7, and 14 days post-transplantation by immunofluorescence double labeling. Although the GFP⁺/α-SMA⁺- and GFP⁺/VIM⁺-cell numbers decreased gradually with healing time, α-SMA⁺- and VIM⁺-cell numbers significantly increased, most of them were endogenous functional cells which were related to angiogenesis and collagen fiber structural remodeling. Conclusion: Therefore, in the initial stage of wound healing, transplanted MSCs differentiated into functional cells and played paracrine roles to recruit more endogenous cells for tissue remodeling. With the disappearance of exogenous cells, endogenous cells were responsible for the latter stage of cutaneous wound healing.

Biopatterned CTLA4/Fc Matrices Facilitate Local Immunomodulation, Engraftment, and Glucose Homeostasis After Pancreatic Islet Transplantation.

Pancreatic islet transplantation (PIT) represents a potential therapy to circumvent the need for exogenous insulin in type 1 diabetes. However, PIT remains limited by lack of donor islets and the need for long-term multidrug immunosuppression to prevent alloimmune islet rejection. Our goal was to evaluate a local immunoregulatory strategy that sustains islet allograft survival and restores glucose homeostasis in the absence of systemic immunosuppression. Nanogram quantities of murine CTLA4/Fc fusion protein were controllably delivered within human acellular dermal matrix scaffolds using an inkjet-based biopatterning technology and cotransplanted with allogeneic islets under the renal capsule to create an immunoregulatory microenvironment around the islet allograft. We achieved long-term engraftment of small loads of allogeneic islet cells with 40% of MHC-mismatched mouse recipients maintaining sustained normoglycemia following pancreatic β-cell ablation by streptozotocin. Biopatterned CTLA4/Fc local therapy was associated with expansion of Foxp3+ regulatory T cells and shifts in cytokine production and gene expression from proinflammatory to regulatory profiles, thus substantially benefiting islet allografts survival and function. This study is a new paradigm for targeted therapies in PIT that demonstrates the favorable effects of immune alterations in the transplant milieu and suggests a unique strategy for minimizing systemic immunosuppression and promoting islet allograft survival.

Composite Skin Grafting with Human Acellular Dermal Matrix Scaffold for Treatment of Diabetic Foot Ulcers: A Randomized Controlled Trial

Composite split-thickness skin grafting (STSG) with acellular dermal matrix (ADM) has been used successfully in burn injuries and trauma, but its use in treating diabetic foot ulcers (DFUs) has not been reported to date. This study investigated the efficacy and safety of composite STSG with ADM in the treatment of DFUs. Fifty-two patients with DFUs were randomized into experimental and control groups. Patients in the experimental group received composite STSG over ADM; the control group received STSG alone. The primary end point was recurrence rate 12 months after grafting. Secondary end points were the healing quality of the grafted site according to Manchester Scar Scale and complete wound closure and complication rates. The number of patients that experienced recurrence was significantly less in the experimental group compared with the control group (4.3% vs 22.7%; p= 0.02). The autografted sites of the experimental group had better appearance and lower Manchester Scar Scale scores (median 9 [interquartile range 8 to 10.25] vs median 11 [interquartile range 10 to 12]; p=0.006). Rates of complete wound closure by weeks 2, 4, and 8 were similar, as were the rates of complications by post-grafting week 4 (38.5% vs 26.9%; p= 0.38). Composite STSG over an ADM scaffold provides an effective method to treat DFUs, withlower recurrence rates and better physical attributes compared with the traditional STSG method. Complete wound closure and complication rates were comparable between these methods.

A novel porcine acellular dermal matrix scaffold used in periodontal regeneration.

Regeneration of periodontal tissue is the most promising method for restoring periodontal structures. To find a suitable bioactive three-dimensional scaffold promoting cell proliferation and differentiation is critical in periodontal tissue engineering. The objective of this study was to evaluate the biocompatibility of a novel porcine acellular dermal matrix as periodontal tissue scaffolds both in vitro and in vivo. The scaffolds in this study were purified porcine acellular dermal matrix (PADM) and hydroxyapatite-treated PADM (HA-PADM). The biodegradation patterns of the scaffolds were evaluated in vitro. The biocompatibility of the scaffolds in vivo was assessed by implanting them into the sacrospinal muscle of 20 New Zealand white rabbits. The hPDL cells were cultured with PADM or HA-PADM scaffolds for 3, 7, 14, 21 and 28 days. Cell viability assay, scanning electron microscopy (SEM), hematoxylin and eosin (H&E) staining, immunohistochemistry and confocal microscopy were used to evaluate the biocompatibility of the scaffolds. In vitro, both PADM and HA-PADM scaffolds displayed appropriate biodegradation pattern, and also, demonstrated favorable tissue compatibility without tissue necrosis, fibrosis and other abnormal response. The absorbance readings of the WST-1 assay were increased with the time course, suggesting the cell proliferation in the scaffolds. The hPDL cells attaching, spreading and morphology on the surface of the scaffold were visualized by SEM, H&E staining, immnuohistochemistry and confocal microscopy, demonstrated that hPDL cells were able to grow into the HA-PADM scaffolds and the amount of cells were growing up in the course of time. This study proved that HA-PADM scaffold had good biocompatibility in animals in vivo and appropriate biodegrading characteristics in vitro. The hPDL cells were able to proliferate and migrate into the scaffold. These observations may suggest that HA-PADM scaffold is a potential cell carrier for periodontal tissue regeneration.