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BACKGROUND:Vascularization is essential for wound healing and functional recovery during soft tissue repair.Adipose tissue is believed to be the body's largest source of stem cells,and a number of different fat complexes have been developed for research and treatment.Its ability to promote angiogenesis and soft tissue repair has been extensively studied. OBJECTIVE:To review the progress of vascularization in soft tissue repair,and to summarize the preparation methods of adipose tissue and its derivative and their applications in vascularization and soft tissue repair.It is proven that adipose tissue and its derivative have excellent research value and clinical application prospects in vascular and soft tissue engineering. METHODS:PubMed,Web of Science and CNKI databases were used to search the related articles published from January 2010 to February 2023.The search terms were"soft tissue repair,wound healing,vascularization,angiogenesis,adipose tissue,stromal vascular fraction,adipose tissue-derived microvascular fragment,nanofat,adipose extracellular matrix/stromal vascular fraction gel"in Chinese and English.A small number of old classic literature was also included.An initial screening was performed by reading the titles and abstracts to exclude literature that was not relevant to the topic of the article,and 69 papers were finally included for the analysis of the result. RESULTS AND CONCLUSION:(1)Wound healing is an important physiological process,which mainly occurs when tissue is damaged,such as injury,surgery,burn,tumor,infection and vascular disease caused by tissue damage and defects.(2)Adequate vascularization of the wound site is essential for tissue repair,reconstruction of local homeostasis and functional recovery.(3)Adipose tissue is believed to be the body's largest pool of stem cells and a number of different fat components have been used for research and treatment.(4)Due to its inherent composition and preparation advantages,adipose tissue will continue to play an important role in tissue engineering research and therapy.
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BACKGROUND:Due to the mechanical properties,unstable drug release,single function and other problems of pure hydrogel materials,in recent years,researchers have prepared a variety of metal organic frameworks-based hydrogel materials by introducing metal organic frameworks into hydrogel,and showed great potential in the field of soft and hard tissue regeneration. OBJECTIVE:To classify the metal organic frameworks-based hydrogel materials based on how metal organic frameworks enhance the properties of hydrogel and further summarize its recent research in the field of soft and hard tissue regeneration,in order to provide ideas and theoretical supports for the subsequent in-depth research on synthesis mechanism and clinical application of the composite material. METHODS:Using"metal organic frameworks,hydrogels,tissue engineering,tissue,bone regeneration,bone,wound"as English and Chinese search terms,we searched Web of Science,PubMed,CNKI,and Wanfang databases.The search period ranged from January 2000 to August 2023.By reading the titles and abstracts,the repetitive studies and unrelated literature of Chinese and English literature were excluded.After the literature quality evaluation,73 articles were included for review. RESULTS AND CONCLUSION:(1)Metal organic frameworks-based hydrogel materials effectively solve the problems of poor mechanical properties,unstable drug release and single function of pure hydrogel.(2)Metal organic frameworks enhance the capacity of repair and regeneration by strengthening the cross-linking of hydrogel,the drug delivery capacity of hydrogel and the multifunction of hydrogel.(3)In terms of hard tissue repair,it has shown good repair effects in animal models of diseases such as bone defects,osteoarthritis,and cartilage defects,suggesting potential application prospects in clinical repair.(4)In terms of soft tissue regeneration,it has the capacities of hemostasis,antibacterial,inflammatory state regulation,oxidative stress state regulation,promoting angiogenesis and other functions,effectively improving the microenvironment of various complex wounds and promoting soft tissue regeneration.(5)Although metal organic frameworks-based hydrogels have many excellent properties,they are still in the initial stage and there are some urgent problems to be solved in the process of clinical transformation,such as the cytotoxicity of metal organic frameworks and large-scale synthesis of metal organic frameworks.(6)With further research,metal organic frameworks-based hydrogels have broad application prospects in the field of soft and hard tissue repair.
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Objective·To construct a self-healing injectable hyaluronic acid(HA)-based hydrogel(HAPD-Cu)and investigate the effects of different copper ions on the properties of the hydrogel and its vasogenic effiicacy to evaluate its feasibility for clinical wound healing.Methods·Bisphosphonated hyaluronic acid(HAPD)was prepared via a blue-light mediated thiol-ene click reaction between thiolated hyaluronic acid(HASH)and acrylated bisphosphonate(Ac-PD)in the presence of photoinitiator 2959.Then,HAPD was further interacted with Cu2+through metal coordination to prepare HAPD-Cu hydrogels with different Cu2+concentrations,i.e.HAPD-Cu1,HAPD-Cu2,HAPD-Cu3 and HAPD-Cu4.The molecular structures of HASH,Ac-PD,HAPD and HAPD-Cu were verified with 1HNMR and FTIR.Microscopic morphology of HAPD-Cu was observed under SEM.The shear-thinning and self-healing properties of HAPD-Cu were verified by rheometer.The Cu2+release from HAPD-Cu was determined with ICP.Live-dead staining and CCK-8 assay were applied to evaluate the biocompatibility of HAPD-Cu.The in vitro vasculogenic activity of HAPD-Cu was determined by a tubule-forming assay with human umbilical vein vascular endothelial cells and the in vivo vasculogenic activity of HAPD-Cu was assessed by CD31 tissue staining.A rat wound defect model was established in vitro to evaluate its actual repair effect.Results·The preparation of the materials was demonstrated through chemical qualitative and quantitative analytical means.In vitro studies showed that all HAPD-Cu with a loose porous internal structure exhibited outstanding self-healing,injectability and degradability,with a one-week degradation cycle and abrupt release behavior,which can meet the needs of wound healing cycle.All HAPD-Cu showed good biocompatibility except HAPD-Cu4,due to its high Cu2+concentrations.Moreover,its angiogenic effect in vitro or in vivo was enhanced with increasing Cu2+concentrations within the permissible Cu2+concentration range.In vitro wound model experiments also showed that the HAPD-Cu hydrogel significantly promoted wound healing compared with the control group.Conclusion·HAPD-Cu hydrogel constructed via the metal coordination shows excellent shape plasticity,allowing the filling of defective sites in a minimally invasive form,and the release of Cu2+greatly facilitates the establishment of early vascular networks,with giant potential for use in the repair of clinically irregular wounds.
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Objective: To explore the possibility of constructing tissue engineered adipose by adipose tissue derived extracellular vesicles (hAT-EV) combined with decellularized adipose tissue (DAT) scaffolds, and to provide a new therapy for soft tissue defects. Methods: The adipose tissue voluntarily donated by the liposuction patient was divided into two parts, one of them was decellularized and observed by HE and Masson staining and scanning electron microscope (SEM). Immunohistochemical staining and Western blot detection for collagen type Ⅰ and Ⅳ and laminin were also employed. Another one was incubated with exosome-removed complete medium for 48 hours, then centrifuged to collect the medium and to obtain hAT-EV via ultracentrifugation. The morphology of hAT-EV was observed by transmission electron microscopy; the nanoparticle tracking analyzer (NanoSight) was used to analyze the size distribution; Western blot was used to analyse membrane surface protein of hAT-EV. Adipose derived stem cells (ADSCs) were co-cultured with PKH26 fluorescently labeled hAT-EV, confocal fluorescence microscopy was used to observe the uptake of hAT-EV by ADSCs. Oil red O staining was used to evaluate adipogenic differentiation after hAT-EV and ADSCs co-cultured for 15 days. The DAT was scissored and then injected into the bilateral backs of 8 C57 mice (6-week-old). In experimental group, 0.2 mL hAT-EV was injected weekly, and 0.2 mL PBS was injected weekly in control group. After 12 weeks, the mice were sacrificed, and the new fat organisms on both sides were weighed. The amount of new fat was evaluated by HE and peri-lipoprotein immunofluorescence staining to evaluate the ability of hAT-EV to induce adipogenesis in vivo. Results: After acellularization of adipose tissue, HE and Masson staining showed that DAT was mainly composed of loosely arranged collagen with no nucleus; SEM showed that no cells and cell fragments were found in DAT, and thick fibrous collagen bundles could be seen; immunohistochemical staining and Western blot detection showed that collagen type Ⅰ and Ⅳ and laminin were retained in DAT. It was found that hAT-EV exhibited a spherical shape of double-layer envelope, with high expressions of CD63, apoptosis-inducible factor 6 interacting protein antibody, tumor susceptibility gene 101, and the particle size of 97.9% hAT-EV ranged from 32.67 nmto 220.20 nm with a peak at 91.28 nm. Confocal fluorescence microscopy and oil red O staining showed that hAT-EV was absorbed by ADSCs and induced adipogenic differentiation. In vivo experiments showed that the wet weight of fat new organisms in the experimental group was significantly higher than that in the control group ( t=2.278, P=0.048). HE staining showed that the structure of lipid droplets in the experimental group was more than that in the control group, and the collagen content in the control group was higher than that in the experimental group. The proportion of new fat in the experimental group was significantly higher than that in the control group ( t=4.648, P=0.017). Conclusion: DAT carrying hAT-EV can be used as a new method to induce adipose tissue regeneration and has a potential application prospect in the repair of soft tissue defects.
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BACKGROUND: Construction of seedless tissue-engineered adipose tissue from acellular adipose tissue is a hot research topic in soft tissue filling. OBJECTIVE: To investigate the effects of preparation methods of acellular adipose tissue on the induction of adipose regeneration after transplantation in recent years, and to look forward to its clinical application prospects. METHODS: A computer-based online search of PubMed and Elsevier databases was performed to retrieve papers regarding acellular adipose tissue preparation and transplantation published between January 1971 and December 2018 with the search terms “adipose tissue engineering; adipose tissue extracellular matrix; soft tissue repair; angiogenesis; adipogenic induction”. The retrieved papers were summarized from the perspectives of improvement in preparation methods of acellular adipose tissue, cross-linking cytokines and biomaterials. RESULTS AND CONCLUSION: Retrieved studies have shown that extracellular matrix of adipose tissue can act as an ideal scaffold material for soft tissue filling. Subcutaneous implantation of extracellular matrix of adipose tissue can recruit host stem cells and induce their proliferation and adipogenesis. However, existing acellular schemes can lead to the loss of extracellular matrix proteins and structures. This greatly affects the fat regeneration ability of acellular adipose tissue implanted in vivo. However, supercritical carbon dioxide deoiling, mechanical pretreatment, cross-linking cytokines or biomaterials can reduce the loss of extracellular matrix proteins and supplement the proteins that promote tissue regeneration during the preparation of acellular adipose tissue. This can ultimately enhance the angiogenesis and adipogenesis of acellular adipose tissue after transplantation. Acellular adipose tissue has strong application prospects in adipose tissue engineering because of its natural adipogenic induction ability. If the loss of extracellular matrix protein can be overcome during preparation of acellular adipose tissue or under the premise of safety and controllability, acellular adipose tissue is expected to become a suitable soft tissue filler that allows allogeneic injection and in situ adipogenesis.
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Objective@#To explore the clinical application effects of autologous platelet-rich plasma gel in the repair of various chronic wounds.@*Methods@#From January 2015 to January 2018, 76 patients with chronic wounds were admitted to our unit, with 39 men and 37 women, aged 28 to 75 (52±6) years. Before the operation, areas of wounds ranged from 2.0 cm×0.5 cm to 17.0 cm×5.0 cm, depths of wounds ranged from 1 to 6 cm, areas of wounds substrate ranged from 3 cm×3 cm to 17 cm×8 cm, and volumes of deep cavities ranged from 7 to 55 mL. All patients received operation 2 to 7 days after admission. Autologous platelet of 220-250 mL was collected from each patient by single extraction to make platelet-rich plasma of 10-50 mL. The cavity was filled completely by injection of platelet-rich plasma gel for 1-3 times. Wounds were sutured directly or covered by local flaps or other materials according to the conditions of wounds, and the unclosed wounds in primary stage were treated by continuous vacuum sealing drainage (VSD). Ultrasound, CT, or magnetic resonance imaging was performed to detect the healing of cavity after the operation. The healing of wound and repair of cavity after the operation and during follow-up were observed.@*Results@#Wounds in 39 patients were closed directly after primary operation. Among them, wounds of 36 patients were healed completely, and wounds of the other 3 patients were healed completely after second debridement and topical filling of platelet-rich plasma gel. The cavities in 35 patients were filled with granulation tissue after treatment of platelet-rich plasma gel for 1-3 times combined with VSD, and the wounds were healed after skin grafting or flap transplantation. The treatment of wounds discontinued in the other 2 patients after treatment of platelet-rich plasma gel for once. Postoperative follow-up was lost in 7 patients. During follow-up of 2 and/or 4 months after the primary operation, wounds were healed well with no recurrence, and cavities were filled with fibrous tissue.@*Conclusions@#Autologous platelet-rich plasma gel has advantages in treating chronic wounds, including a large amount by single extraction, flexible use mode, ability to fully fill the complex cavity, high surgical safety, and mild secondary injury. It′s a new choice for repair of chronic wounds in clinic.