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Recent cumulative findings signify the adaptive immunity of materials as a key agenda in tissue healing that can improve regenerative events and outcomes. Modulating immune responses, mainly the recruitment and functions of T and B cells and their further interplay with innate immune cells (e.g., dendritic cells, macrophages) can be orchestrated by materials. For instance, decellularized matrices have been shown to promote muscle healing by inducing T helper 2 (Th2) cell immunity, while synthetic biopolymers exhibit differential effects on B cell responses and fibrosis compared decellularized matrices. We discuss the recent findings on how implantable materials instruct the adaptive immune events and the subsequent tissue healing process. In particular, we dissect the materials’ physicochemical properties (shape, size, topology, degradation, rigidity, and matrix dynamic mechanics) to demonstrate the relations of these parameters with the adaptive immune responses in vitro and the underlying biological mechanisms. Furthermore, we present evidence of recent in vivo phenomena, including tissue healing, cancer progression, and fibrosis, wherein biomaterials potentially shape adaptive immune cell functions and in vivo outcomes. Our discussion will help understand the materials-regulated immunology events more deeply, and offer the design rationale of materials with tunable matrix properties for accelerated tissue repair and regeneration.

Purpose We aim to conduct a literature review on actions of platelet-rich fibrin (PRF), preclinical studies in PRF utility, and its potential uses in clinical settings. Methods We conducted a literature review based on primary studies conducted on PubMed and Europe PMC between 2012 and 2022. We included 42 articles in this review from the results of our search. Results Epithelial tissues act as a barrier from mechanical, chemical, and temperature damage. Naturally, hemostasis acts to reduce blood loss and creates initial fibrin matrices after traumatic events or injuries. PRF is a second-generation platelet concentrate, commonly made in the form of leukocyte and PRF due to leukocyte content. Fibrin matrices in PRF allow more sustained growth factors release when compared to PRP, the first-generation platelet concentrate. PRF comes from increased proliferation and differentiation mediated by reduced proliferation of inflammatory cells and sustained release of growth factors and cytokines. Conclusions PRF action comes from increased proliferation and differentiation from growth factors and cytokines. PRF may reduce inflammation and fibrosis to improve soft-tissue and bone healing and allow for better graft integration.

Purpose: The present study aimed to evaluate and compare the management of Jump space (JS) in immediate implants with and without Demineralised freeze-dried bone allograft (DFDBA) with flapless approach. Materials and Methods: The present study included 40 sites with immediate implant placement in the maxillary anterior region. Group 1 patients were treated without augmentation while Group 2 patients with DFDBA in the JS. Both the groups were further subdivided according to the horizontal dimensions as JS less (G1S1, G2S1) or more than 2mm (G1S2, G2S2). Plaque index (PI), Gingival Index (GI), Probing depth (PD), Testori esthetic score (TS), VAS score, Crestal Bone height (CBH), Ridge width (RW), Vertical distance (VD) and radiolucent area (RA) were evaluated radiographically with CBCT at baseline and 12 months' post therapy. Results: Significant differences were observed in CBH in the midfacial region in G1S1-G2S1 with the mean of 0.34±0.19mm and G1S2 --G2S2 with 0.75±0.26 mm at 12 months. Significant differences in TS were observed in G1S1 and G2S1 with mean value of 0.55±0.53 while G1S2 and G2S2 exhibited value of 1.33±0.82. Conclusion: DFDBA shows better CBH preservation in midfacial region, reduction in RA indicating greater resolution of JS thereby leading to better hard and soft tissue healing. [ABSTRACT FROM AUTHOR]

Introduction: Foraminal Enlargement (FE) is a cleaning performed in the apical-most region of the tooth, in order to optimize root disinfection. This systematic review evaluated the influence of FE during root canal treatment on bacterial reduction and repair of the periapical lesion. Materials and Methods: Searches in PubMed/MEDLINE, Scopus, Cochrane Library, Web of Science, Embase, Scielo, Lilacs and OpenGrey were performed until January-2024. Ex vivo and in vivo studies evaluating the effects of FE in the bacterial reduction and repair of the periapical lesion were included, respectively, followed by risk of bias assessment (modified version of Joanna Briggs Institute's for ex vivo studies and Corresponding author Gustavo Systematic Review Centre for Laboratory animal Experimentation's risk of bias tools for in vivo studies). The meta-analysis was not feasible and a qualitative summary for each outcome was provided. Results: Of 950 studies, 2 in vivo studies were eligible, using animal models with infected teeth. Of these two, periapical repair was evaluated with hematoxylin-eosin stain, and FE improved periapical healing. Regarding ex vivo studies, 3 were eligible, using extracted human teeth. The inoculations in ex vivo models were performed with Enterococcus (E.) faecalis, and FE reduced E. faecalis in the ex vivo models. Conclusions: Foraminal enlargement seems to increase bacterial reduction within the root canal, and provide major periapical tissue repair on the histological analysis in animal studies. However, caution is necessary when translating these results to the clinical environment. [ABSTRACT FROM AUTHOR]

This study aimed to investigate the anti‐inflammatory and wound healing effects of the polysaccharide extract from Opuntia ficus‐indica cladodes (TPL‐Ofi) using a rat cutaneous wound model. After anaesthesia, four 7‐mm‐diameter dorsal wounds per animal (n = 6/group for each experimental day of evaluation) were created in female Wistar rats using a surgical punch. The animals were treated topically twice daily with TPL‐Ofi (0.01–1%; treated group) or sterile saline (control group) for a period of 21 days. Ulcerated tissue was collected for analysis of histological parameters (inflammation score, number of polymorphonuclear, mononuclear, fibroblast/myofibroblasts and blood vessels), immunohistochemical (fibroblast growth factor 2 [FGF‐2]) and oxidative stress markers (myeloperoxidase [MPO] and glutathione [GSH]). After 21 days of treatment, body weight, net organ weight and plasma biochemical levels were measured. TPL‐Ofi, containing a total carbohydrate content of 65.5% and uronic acid at 2.8%, reduced oedema on the second day and increased the nociceptive threshold on the second and third days. TPL‐Ofi reduced mononuclear infiltrate on the second and MPO activity on the fifth day. TPL‐Ofi increased GSH levels on the second day, as well as fibroblast/myofibroblasts counts, neoangiogenesis and FGF‐2 levels on the fifth and seventh days. No changes were observed in body weight, net organ weight or toxicology assessment. Topical application of TPL‐Ofi exhibited anti‐inflammatory and antinociceptive effects, ultimately improving wound healing in cutaneous wounds. [ABSTRACT FROM AUTHOR]

To reduce and prevent postsurgical adhesions, a variety of scientific approaches have been suggested and applied. This includes the use of advanced therapies like tissue-engineered (TE) biomaterials and scaffolds. Currently, biocompatible antiadhesive constructs play a pivotal role in managing postoperative adhesions and several biopolymer-based products, namely hyaluronic acid (HA) and polyethylene glycol (PEG), are available on the market in different forms (e.g., sprays, hydrogels). TE polymeric constructs are usually associated with critical limitations like poor biocompatibility and mechanical properties. Hence, biocompatible nanocomposites have emerged as an advanced therapy for postoperative adhesion treatment, with hydrogels and electrospun nanofibers among the most utilized antiadhesive nanocomposites for in vitro and in vivo experiments. Recent studies have revealed that nanocomposites can be engineered to generate smart three-dimensional (3D) scaffolds that can respond to different stimuli, such as pH changes. Additionally, nanocomposites can act as multifunctional materials for the prevention of adhesions and bacterial infections, as well as tissue healing acceleration. Still, more research is needed to reveal the clinical potential of nanocomposite constructs and the possible success of nanocomposite-based products in the biomedical market. [ABSTRACT FROM AUTHOR]

Enteric fistula (EF), a serious complication after abdominal surgery, refers to unnatural communication between the gastrointestinal tract and the skin or other hollow organs. It is associated with infection, massive fluid/electrolyte loss, and malnutrition, resulting in an unhealed course. Despite advances in surgical techniques, wound care, infection control, and nutritional support, EF remains associated with considerable morbidity and mortality. Autologous platelet-rich plasma (PRP) containing elevated platelet concentrations has been proposed to promote healing in many tissues. However, the mechanism of action of PRP in EF treatment remains unclear owing to its complicated clinical manifestations. In this review, we summarized the clinical approaches, outlined the principal cytokines involved in the healing effects, and discussed the advantages of PRP for EF therapy. In addition, we defined the mechanism of autologous PRP in EF management, which is essential for further developing EF therapies.

The application of traditional materials to tissue healing in sports rehabilitation training has problems such as poor effect, high rejection reaction, and slow healing speed. It also brings many challenges to the development of sports rehabilitation training. This article aims to explore the impact of composite conjugated materials on tissue healing to promote rapid and efficient tissue healing and improve the effect of sports rehabilitation training. Through research and analysis, this article found that composite conjugated materials have unique biocompatibility and can promote cell growth and differentiation. In skin tissue healing, composite conjugated materials can control the release rate and duration of drugs to promote skin healing. During the fracture healing process, conjugated materials can provide growth factors and extracellular matrix components, stimulate bone cell proliferation and differentiation, and promote fracture healing. In terms of soft tissue injuries, composite conjugated materials serve as supporting structures or matrices, providing a favorable environment for the regeneration of damaged tissue. In the regulation of inflammatory responses, composite conjugated materials reduce inflammatory responses and accelerate the healing process by modulating immune responses. The results of this study show that 1 week after the experiment, the skin healing rates of the control group and the experimental group were 42.55% and 58.17% respectively; 5 weeks after the experiment, the skin healing rates of the control group and the experimental group were 51.28% and 73.24% respectively. After 1, 2, 3, 4, and 5 weeks of experiment, it was found that the average tissue repair rates of the control group were 44.03%, 54.18%, 58.40%, 67.08%, and 72.09% respectively, and the average tissue repair rates of the experimental group were 52.18%, 61.91%, 63.40%, 74.61%, and 85.05% respectively. This study highlights the huge potential of composite conjugated materials in promoting tissue healing and tissue repair, and is of great significance for promoting technological progress in the field of sports rehabilitation and improving rehabilitation effects.

Wound healing is a complex and meticulously orchestrated process involving multiple phases and cellular interactions. This narrative review explores the intricate mechanisms behind wound healing, emphasizing the significance of cellular processes and molecular factors. The phases of wound healing are discussed, focusing on the roles of immune cells, growth factors, and extracellular matrix components. Cellular shape alterations driven by cytoskeletal modulation and the influence of the 'Formin' protein family are highlighted for their impact on wound healing processes. This review delves into the use of absorbable meshes in wound repair, discussing their categories and applications in different surgical scenarios. Interleukins (IL-2 and IL-6), CD31, CD34, platelet rich plasma (PRP), and adipose tissue-derived mesenchymal stem cells (ADSCs) are discussed in their respective roles in wound healing. The interactions between these factors and their potential synergies with absorbable meshes are explored, shedding light on how these combinations might enhance the healing process. Recent advances and challenges in the field are also presented, including insights into mesh integration, biocompatibility, infection prevention, and postoperative complications. This review underscores the importance of patient-specific factors and surgical techniques in optimizing mesh placement and healing outcomes. As wound healing remains a dynamic field, this narrative review provides a comprehensive overview of the current understanding and potential avenues for future research and clinical applications. [ABSTRACT FROM AUTHOR]

The recent findings showed that the superficial fascia is a fibrous layer in the middle of hypodermis, richly innervated and vascularized, and more complex than so far demonstrated. This study showed the presence of mast cells in the superficial fascia of the human abdomen wall of three adult volunteer patients (mean age 42 ± 4 years; 2 females, 1 male), by Toluidine Blue and Safranin-O stains and Transmission Electron Microscopy. Mast cells are distributed among the collagen bundles and the elastic fibers, near the vessels and close to the nerves supplying the tissue, with an average density of 20.4 ± 9.4/mm2. The demonstration of the presence of mast cells in the human superficial fascia highlights the possible involvement of the tissue in the inflammatory process, and in tissue healing and regeneration processes. A clear knowledge of this anatomical structure of the hypodermis is fundamental for a good comprehension of some fascial dysfunctions and for a better-targeted clinical practice. [ABSTRACT FROM AUTHOR]

Easy recurrence and bacteria infected-wound healing after surgery excision pose severe challenges to clinical melanoma therapy. Herein, an injectable CuO2 nanodots-engineered thermosensitive chitosan hydrogel (CuO2–BSO@Gel) for enhanced melanoma chemo-sonodynamic therapy and improved infected wound healing was rationally constructed by facilely integrating the CuO2 nanodots and L-Buthionine-(S, R)-sulfoximine (BSO) with thermoresponsive hydrogel. Favored by the Fenton catalytic activity of Cu2+, the CuO2 nanodots can achieve enhanced chemodynamic therapy (CDT) by self-supplying H2O2 under acidic tumor microenvironment. Simultaneously, the CuO2 nanodots with a narrow bandgap (2.29 ​eV) were proven to be the efficient sonosensitizers, and the corresponding quantum yield of singlet oxygen (1O2) could be boosted by the O2 generation during Fenton-like reactions. Additionally, combining with the glutathione (GSH) depletion of loaded BSO, intracellular oxidative stress induced by SDT and CDT was further amplified, leading to the specific ferroptosis. Importantly, this multifunctional hydrogel significantly promoted the proliferation of normal skin cells and accelerated the bacteria-infected wound healing by the effective chemo-sonodynamic antibacterial activity and the enhanced angiogenesis. Thus, the engineered thermogel features the distinct chemo-sonodynamic performance, desirable biocompatibility and bioactivity, providing a competitive strategy for eradicating melanoma and infected wound healing.

To reduce and prevent postsurgical adhesions, a variety of scientific approaches have been suggested and applied. This includes the use of advanced therapies like tissue-engineered (TE) biomaterials and scaffolds. Currently, biocompatible antiadhesive constructs play a pivotal role in managing postoperative adhesions and several biopolymer-based products, namely hyaluronic acid (HA) and polyethylene glycol (PEG), are available on the market in different forms (e.g., sprays, hydrogels). TE polymeric constructs are usually associated with critical limitations like poor biocompatibility and mechanical properties. Hence, biocompatible nanocomposites have emerged as an advanced therapy for postoperative adhesion treatment, with hydrogels and electrospun nanofibers among the most utilized antiadhesive nanocomposites for in vitro and in vivo experiments. Recent studies have revealed that nanocomposites can be engineered to generate smart three-dimensional (3D) scaffolds that can respond to different stimuli, such as pH changes. Additionally, nanocomposites can act as multifunctional materials for the prevention of adhesions and bacterial infections, as well as tissue healing acceleration. Still, more research is needed to reveal the clinical potential of nanocomposite constructs and the possible success of nanocomposite-based products in the biomedical market.

Background: Ultraviolet (UV) irradiation can modulate host immune responses and this approach is a novel application for treating endodontic infections and inflammation in root canals. Methods: A dataset of UV-induced molecules was compiled from a literature search. A subset of this dataset was used to calculate expression log2 ratios of endodontic tissue molecules from HEPM cells and gingival fibroblasts after 255, 405, and 255/405 nm UV irradiation. Both datasets were analyzed using ingenuity pathway analysis (IPA, Qiagen, Germantown, MD, USA). Statistical significance was calculated using Fisher's exact test and z-scores were calculated for IPA comparison analysis. Results: The dataset of 32 UV-induced molecules contained 9 antimicrobial peptides, 10 cytokines, 6 growth factors, 3 enzymes, 2 transmembrane receptors, and 2 transcription regulators. These molecules were in the IPA canonical pathway annotations for the wound healing signaling pathway (9/32, p = 3.22 × 10−11) and communication between immune cells (6/32, p = 8.74 × 10−11). In the IPA disease and function annotations, the 32 molecules were associated with an antimicrobial response, cell-to-cell signaling and interaction, cellular movement, hematological system development and function, immune cell trafficking, and inflammatory response. In IPA comparison analysis of the 13 molecules, the predicted activation or inhibition of pathways depended upon the cell type exposed, the wavelength of the UV irradiation used, and the time after exposure. Conclusions: UV irradiation activates and inhibits cellular pathways and immune functions. These results suggested that UV irradiation can activate innate and adaptive immune responses, which may supplement endodontic procedures to reduce infection, inflammation, and pain and assist tissues to heal. [ABSTRACT FROM AUTHOR]

Keywords: vitamin C; ascorbic acid; healing; wound healing; tissue healing; supplementation EN vitamin C ascorbic acid healing wound healing tissue healing supplementation N.PAG N.PAG 12 08/29/22 20220801 NES 220801 1. Many of the studies did not measure baseline vitamin C levels and, therefore, it is unknown whether those patients with a baseline deficiency would benefit from supplementation when compared to patients with normal baseline vitamin C levels. It is important to note that serum vitamin C was not measured, and, therefore, that it is unknown whether those with a baseline vitamin C deficiency would benefit from supplementation following a fracture. After two weeks the vitamin C levels of all patients in the vitamin C group had significantly increased and were also greater than those in the placebo group [[13]]. [Extracted from the article]

Tendon injuries are a major part of musculoskeletal injuries in animals, particularly in horses. So far, no complete cure has been found for this disease, and most treatments focus on pain control. The advantages of using exosomes over cell-based therapies and the effects of mesenchymal stem cells (MSCs) on tissue repair suggest exosomes derived from MSCs as an appropriate treatment option in repairing tendon injuries. This paper aimed to review various protocols for exosome isolation and the role of MSCs- derived exosomes on tendon tissue repair of animals, especially in horses. In the treatment of tendon disorders, exosomes are more stable than cells, have a lower risk of immune rejection after allogeneic administration, and can be used as an appropriate alternative therapy. Exosomes derived from MSCs of different sources stimulate the proliferation and migration of tenocytes and fibroblasts, mod-ulate collagen fiber arrangement, macrophage functions, and inflammatory responses, inhibit adhesion, and generally repair damaged tendons. Exosomes are involved in cell-cell communication due to the exchange of pro-teins and genetic materials. The use of MSCs-derived exosomes is considered a treatment option due to easier maintenance and reduction of the risk of rejection by the immune system, reducing the possibility of aneuploidy compared to cell-based methods

Minimally invasive transcatheter interventional therapy utilizing cardiac occluders represents the primary approach for addressing congenital heart defects and left atrial appendage (LAA) thrombosis. However, incomplete endothelialization and delayed tissue healing after occluder implantation collectively compromise clinical efficacy. In this study, we have customized a recombinant humanized collagen type I (rhCol I) and developed an rhCol I-based extracellular matrix (ECM)-mimetic coating. The innovative coating integrates metal-phenolic networks with anticoagulation and anti-inflammatory functions as a weak cross-linker, combining them with specifically engineered rhCol I that exhibits high cell adhesion activity and elicits a low inflammatory response. The amalgamation, driven by multiple forces, effectively serves to functionalize implantable materials, thereby responding positively to the microenvironment following occluder implantation. Experimental findings substantiate the coating's ability to sustain a prolonged anticoagulant effect, enhance the functionality of endothelial cells and cardiomyocyte, and modulate inflammatory responses by polarizing inflammatory cells into an anti-inflammatory phenotype. Notably, occluder implantation in a canine model confirms that the coating expedites reendothelialization process and promotes tissue healing. Collectively, this tailored ECM-mimetic coating presents a promising surface modification strategy for improving the clinical efficacy of cardiac occluders. [Display omitted] [ABSTRACT FROM AUTHOR]

Background: Physiologic and psychologic stress slow healing from experimental wounds by impairing immune function.Objectives: We aimed to determine whether supplemental protein and multinutrient supplementation improved wound healing markers after acute stress induced by acute sleep restriction.Methods: In this single-blind, crossover study in generally healthy young adults (18 males/2 females; mean ± SD age: 19.7 ± 2.30 y), experimental wounds were created by removing the top layer of forearm blisters induced via suction after 48 h of 72-h sleep restriction (2-h nightly sleep), a protocol previously shown to delay wound healing. Skin barrier restoration (measured by transepidermal water loss) assessed wound healing ≤10 d postblistering, and local immune responses were evaluated by serial measurement of cytokine concentrations in fluid collected at wound sites for 48 h postblistering. Participants consumed controlled, isocaloric diets with either 0.900 g · kg-1 · d-1 protein plus placebo (PLA) or 1.50 g · kg-1 · d-1 protein plus multinutrient beverage [l-arginine: 20.0 g/d; l-glutamine: 30.0 g/d; omega-3 (n-3) fatty acids: 1.00 g/d; zinc sulfate: 24.0 mg/d; cholecalciferol: 800 IU/d; and vitamin C: 400 mg/d] (NUT) during sleep restriction and for 4 d afterwards.Results: Skin barrier restoration (primary outcome) was shorter for NUT (median: 3.98 d; IQR: 1.17 d) than for PLA (median: 5.25 d; IQR: 1.05 d) (P = 0.001). Cytokines from wound fluid (secondary outcome) increased over time (main effect of time P ≤ 0.001), except IL-13 (P = 0.07); however, no effects of treatment were observed.Conclusions: Supplemental nutrition may promote wound healing after sleep restriction in healthy adults including military personnel, the latter of which also have a high incidence of wounds and infection.This trial was registered at clinicaltrials.gov as NCT03525184. [ABSTRACT FROM AUTHOR]

Patients with head and neck cancer (HNC) and patients with primary Sjögren's syndrome (pSS) may exhibit similar symptoms of dry mouth and dry eyes, as a result of radiotherapy (RT) or a consequence of disease progression. To identify the proteins that may serve as promising disease biomarkers, we analysed saliva and tears from 29 radiated HNC patients and 21 healthy controls, and saliva from 14 pSS patients by mass spectrometry-based proteomics. The study revealed several upregulated, and in some instances overlapping, proteins in the two patient groups. Histone H1.4 and neutrophil collagenase were upregulated in whole saliva of both patient groups, while caspase-14, histone H4, and protein S100-A9 were upregulated in HNC saliva only. In HCN tear fluid, the most highly upregulated protein was mucin-like protein 1. These overexpressed proteins in saliva and tears play central roles in inflammation, host cell injury, activation of reactive oxygen species, and tissue repair. In conclusion, the similarities and differences in overexpressed proteins detected in saliva from HNC and pSS patients may contribute to the overall understanding of the different pathophysiological mechanisms inducing dry mouth. Thus, the recurring proteins identified could possibly serve as future promising biomarkers [ABSTRACT FROM AUTHOR]

Objective:Postoperative anastomotic leakage is still an issue in modern surgery. Re-hospitalization due to postoperative anastomosis leakage prolongs hospital stay and re-operations increase the cost. There is still no consent on how to dissect the intestines. The objective of the present study is to analyze the safety of colonic anastomoses after dissections using scalpel, scissors and cautery in rats.Method:There were 4 groups of 32 Wistar Hannover adult rodents. Each group consisted of 8 animals: group 1: sham, group 2: scalpel, group 3: scissors, group 4: cautery. Anastomosis was done over a single layer. Bursting pressure (BP) was measured at day 7. Tissue and blood samples were taken for the evaluation of biochemical and histopathological parameters.Results:Statistically significant disparity was seen among the sham, scalpel, scissors and cautery groups regarding the mean BP average, mean hydroxyproline levels and fibrosis distributions.Conclusion:Cautery is the best choice for hemostasis; however, when considering tissue healing, scalpel and the scissors were found to be safest alternatives.

Abstract Purpose Although platelet-rich plasma (PRP) therapy has become an increasingly popular treatment for sports-related injuries, the molecular mechanisms of PRP on tissue healing process remain poorly understood. The aim of the present study was to develop an experimental method quantifying the efficacy of PRP with murine patellar tendon injury model, leading to future elucidation of the mechanisms of PRP on healing processes. Methods Full-thickness defects were created in the central third of the murine patellar tendon. The prepared allogenic PRP gel was applied on the defect of the patellar tendon (PRP group), while the remaining mice served as the untreated control group. Mice were sacrificed at 2, 4, 6, 8, and 10 weeks after the operation, with histological sections obtained in each time point (n = 4 / time point / group). Semi-quantitative histological evaluation was performed in accordance with the Bonar score. The variables included in this scoring system were cell morphology, ground substance, collagen arrangement, and vascularity, with higher grades indicating worse tendon structures. In addition, the ratio of the collagen fibers to the entire tendon tissue (FT ratio) was measured using KS400 software as a quantitative histological evaluation. Results The total Bonar score in the PRP group was significantly lower than in control group. With regard to the variables in the Bonar score, the vascularity score was significantly higher in the PRP group at 2 and 4 weeks, while the collagen arrangement score was significantly lower in the PRP group at 8 weeks. Based on a quantitative evaluation, the recovery speed of the patellar tendon determined by FT ratio was significantly faster in the PRP group than in the control group at 6 and 8 weeks. Conclusions We have developed an experimental method for histological and quantitative evaluation of the effects of PRP on tissue healing using murine patellar tendon injury model. The results of this study suggest that the local application of PRP could enhance the tissue-healing process both directly through action on localized cells and indirectly through the recruitment of reparative cells through the blood flow. Further investigations will be needed to confirm the mechanisms of PRP in tissue-healing processes with the development of this experimental model.

Recent cumulative findings signify the adaptive immunity of materials as a key agenda in tissue healing that can improve regenerative events and outcomes. Modulating immune responses, mainly the recruitment and functions of T and B cells and their further interplay with innate immune cells (e.g., dendritic cells, macrophages) can be orchestrated by materials. For instance, decellularized matrices have been shown to promote muscle healing by inducing T helper 2 (Th2) cell immunity, while synthetic biopolymers exhibit differential effects on B cell responses and fibrosis compared decellularized matrices. We discuss the recent findings on how implantable materials instruct the adaptive immune events and the subsequent tissue healing process. In particular, we dissect the materials' physicochemical properties (shape, size, topology, degradation, rigidity, and matrix dynamic mechanics) to demonstrate the relations of these parameters with the adaptive immune responses in vitro and the underlying biological mechanisms. Furthermore, we present evidence of recent in vivo phenomena, including tissue healing, cancer progression, and fibrosis, wherein biomaterials potentially shape adaptive immune cell functions and in vivo outcomes. Our discussion will help understand the materials-regulated immunology events more deeply, and offer the design rationale of materials with tunable matrix properties for accelerated tissue repair and regeneration., Competing Interests: Kim HW is an editorial board member for Bioactive Materials and was not involved in the editorial review or the decision to publish this article. All authors declare that there are no competing interests., (© 2024 The Authors.)

Tissue healing and regeneration is a complex, choreographed, spatiotemporal process involving a plethora of cell types, the activity of which is stringently regulated in order for effective tissue repair to ensue post injury. A number of globally prevalent conditions such as heart disease, organ failure, and severe musculoskeletal disorders require new therapeutic strategies to repair damaged or diseased tissue, particularly given an ageing population in which obesity, diabetes, and consequent tissue defects have reached epidemic proportions. This is further compounded by the lack of intrinsic healing and poor regenerative capacity of certain adult tissues. While vast progress has been made in the last decade regarding tissue regenerative strategies to direct self-healing, for example, through implantation of tissue engineered scaffolds, several challenges have hampered the clinical application of these technologies. Control of the immune response is growing as an attractive approach in regenerative medicine and it is becoming increasingly apparent that an in depth understanding of the interplay between cells of the immune system and tissue specific progenitor cells is of paramount importance. Furthermore, the integration of immunology and bioengineering promises to elevate the efficacy of biomaterial-based tissue repair and regeneration. In this review, we highlight the role played by individual immune cell subsets in tissue repair processes and describe new approaches that are being taken to direct appropriate healing outcomes via biomaterial mediated targeting of immune cell activity. It is becoming increasingly apparent that controlling the immune response is as an attractive approach in regenerative medicine. Here, we propose that an in-depth understanding of immune system and tissue specific progenitor cell interactions may reveal mechanisms by which tissue healing and regeneration takes place, in addition to identifying novel therapeutic targets that could be used to enhance the tissue repair process. To date, most reviews have focused solely on macrophage subsets. This manuscript details the role of other innate and adaptive immune cells such as innate lymphoid cells (ILCs), natural killer (NK) cells and γδT cells (in addition to macrophages) in tissue healing. We also describe new approaches that are being taken to direct appropriate healing outcomes via biomaterial mediated cytokine and drug delivery. [Display omitted] [ABSTRACT FROM AUTHOR]

Tendon injuries are a major part of musculoskeletal injuries in animals, particularly in horses. So far, no complete cure has been found for this disease, and most treatments focus on pain control. The advantages of using exosomes over cell-based therapies and the effects of mesenchymal stem cells (MSCs) on tissue repair suggest exosomes derived from MSCs as an appropriate treatment option in repairing tendon injuries. This paper aimed to review various protocols for exosome isolation and the role of MSCs-derived exosomes on tendon tissue repair of animals, especially in horses. In the treatment of tendon disorders, exosomes are more stable than cells, have a lower risk of immune rejection after allogeneic administration, and can be used as an appropriate alternative therapy. Exosomes derived from MSCs of different sources stimulate the proliferation and migration of tenocytes and fibroblasts, modulate collagen fiber arrangement, macrophage functions, and inflammatory responses, inhibit adhesion, and generally repair damaged tendons. Exosomes are involved in cell-cell communication due to the exchange of proteins and genetic materials. The use of MSCs-derived exosomes is considered a treatment option due to easier maintenance and reduction of the risk of rejection by the immune system, reducing the possibility of aneuploidy compared to cell-based methods. [ABSTRACT FROM AUTHOR]

Aim: The therapeutic potential of adipose-derived stem cell conditioned medium (ASC-CM) was studied in the rabbit model of critical limb ischemia (CLI). Methods: Rabbits received treatment with ASC-CM or placebo. Gastrocnemius muscle tissue was collected 35 days after ischemia induction. Ischemic changes were evaluated in hematoxylin-eosin stained tissues for early (necrotic lesions/granulation tissue) and late (fibrous scars) phases of tissue repair. The expression of proangiogenic miR-126 was also evaluated using in situ hybridization. The levels of cytokines, insulin, and C-peptide were measured in blood. Results: Early repair phases were observed more often in placebo-treated samples (45.5%) than in ASC-CM-treated ones (22.2%). However, the difference was not statistically significant. We demonstrated a statistically significant positive correlation between the early healing phases in tissue samples and C-peptide levels in peripheral blood. The expression of proangiogenic miR-126 was also shown in a number of structures in all phases of ischemic tissue healing. Conclusion: Based on our results, we believe that treatment with ASC-CM has the potential to accelerate the healing process in ischemic tissues in the rabbit model of CLI. The whole healing process was accompanied by miR-126 tissue expression. C-peptide could be used to monitor the course of the tissue healing process.

Vitamin C is an essential nutrient for humans and animals which are unable to synthesise it themselves. Vitamin C is important for tissue regeneration due to the role it plays in collagen formation, and its antioxidant properties. We reviewed the literature to evaluate potential associations between vitamin C supplementation and healing of an acute or chronic condition. Embase, Medline, PubMed, and the Cochrane Library were searched for studies published prior to April 2022. Studies were eligible if they reported at least one association between vitamin C supplementation and healing outcomes. Eighteen studies met the inclusion criteria and were included in this review. Overall, vitamin C supplementation improved healing outcomes in certain pathologies, predominantly pressure ulcers. However, many of the studies had small sample sizes, combined nutritional treatments, and did not test baseline vitamin C. Future studies should be of larger scale, exclusively using vitamin C to determine its role in tissue healing in other wounds. We recommend consideration of vitamin C supplementation for people with pressure ulcers.

Platelet rich plasma (PRP) has trophic functions due to a high concentration of growth factors and cytokines. These properties may be of therapeutic interest in the management of burn injuries. In preparation for a clinical study at the Lyon Burn Centre on PRP as an inducer of healing in burns, we carried out a review of the literature looking at the results of the use of this therapy. A review of the literature on the use of PRP for the treatment of burn injuries was performed by querying the PUBMED database using the keywords [platelet rich plasma] AND [burns]. Controlled clinical or pre-clinical studies in English or French were included. Eleven articles were identified, consisting of eight preclinical animal model studies and three clinical studies. These looked at the effects of PRP on the healing of burned areas whether they were grafted or not, on the improvement of neuropathic pain, and on distant skin trophicity. The results of recent preclinical studies show shorter epithelialization times thanks to PRP. In humans, a significant study (201 patients) validates its use in combination with thin skin grafts, and another shows benefits on distant cutaneous trophicity. In conclusion, the use of PRP topically or by injection under the skin has a potential benefit in the management of acute burns. A large-scale series validates its use in clinical practice. [ABSTRACT FROM AUTHOR]

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Signaling lipid mediators released from 5 lipoxygenase (5LO) pathways influence both bone and muscle cells, interfering in their proliferation and differentiation capacities. A major limitation to studying inflammatory signaling pathways in bone and muscle healing is the inadequacy of available animal models. We developed a surgical injury model in the vastus lateralis (VL) muscle and femur in 129/SvEv littermates mice to study simultaneous musculoskeletal (MSK) healing in male and female, young (3 months) and aged (18 months) WT mice compared to mice lacking 5LO (5LOKO). MSK defects were surgically created using a 1-mm punch device in the VA muscle followed by a 0.5-mm round defect in the femur. After days 7 and 14 post-surgery, the specimens were removed for microtomography (microCT), histopathology, and immunohistochemistry analyses. In addition, non-injured control skeletal muscles along with femur and L5 vertebrae were analyzed. Bones were microCT phenotyped, revealing that aged female WT mice presented reduced BV/TV and trabecular parameters compared to aged males and aged female 5LOKO mice. Skeletal muscles underwent a customized targeted lipidomics investigation for profiling and quantification of lipid signaling mediators (LMs), evidencing age, and gender related-differences in aged female 5LOKO mice compared to matched WT. Histological analysis revealed a suitable bone-healing process with osteoid deposition at day 7 post-surgery, followed by woven bone at day 14 post-surgery, observed in all young mice. Aged WT females displayed increased inflammatory response at day 7 post-surgery, delayed bone matrix maturation, and increased TRAP immunolabeling at day 14 post-surgery compared to 5LOKO females. Skeletal muscles of aged animals showed higher levels of inflammation in comparison to young controls at day 14 post-surgery; however, inflammatory process was attenuated in aged 5LOKO mice compared to aged WT. In conclusion, this new model shows that MSK healing is influenced by age, gender, and the 5LO pathway, which might serve as a potential target to investigate therapeutic interventions and age-related MSK diseases. Our new model is suitable for bone–muscle crosstalk studies.

Signaling lipid mediators released from 5 lipoxygenase (5LO) pathways influence both bone and muscle cells, interfering in their proliferation and differentiation capacities. A major limitation to studying inflammatory signaling pathways in bone and muscle healing is the inadequacy of available animal models. We developed a surgical injury model in the vastus lateralis (VL) muscle and femur in 129/SvEv littermates mice to study simultaneous musculoskeletal (MSK) healing in male and female, young (3 months) and aged (18 months) WT mice compared to mice lacking 5LO (5LOKO). MSK defects were surgically created using a 1-mm punch device in the VA muscle followed by a 0.5-mm round defect in the femur. After days 7 and 14 post-surgery, the specimens were removed for microtomography (microCT), histopathology, and immunohistochemistry analyses. In addition, non-injured control skeletal muscles along with femur and L5 vertebrae were analyzed. Bones were microCT phenotyped, revealing that aged female WT mice presented reduced BV/TV and trabecular parameters compared to aged males and aged female 5LOKO mice. Skeletal muscles underwent a customized targeted lipidomics investigation for profiling and quantification of lipid signaling mediators (LMs), evidencing age, and gender related-differences in aged female 5LOKO mice compared to matched WT. Histological analysis revealed a suitable bone-healing process with osteoid deposition at day 7 post-surgery, followed by woven bone at day 14 post-surgery, observed in all young mice. Aged WT females displayed increased inflammatory response at day 7 post-surgery, delayed bone matrix maturation, and increased TRAP immunolabeling at day 14 post-surgery compared to 5LOKO females. Skeletal muscles of aged animals showed higher levels of inflammation in comparison to young controls at day 14 post-surgery; however, inflammatory process was attenuated in aged 5LOKO mice compared to aged WT. In conclusion, this new model shows that MSK healing is influenced by age, gender, and the 5LO pathway, which might serve as a potential target to investigate therapeutic interventions and age-related MSK diseases. Our new model is suitable for bone–muscle crosstalk studies. [ABSTRACT FROM AUTHOR]

Purpose: Although platelet-rich plasma (PRP) therapy has become an increasingly popular treatment for sports-related injuries, the molecular mechanisms of PRP on tissue healing process remain poorly understood. The aim of the present study was to develop an experimental method quantifying the efficacy of PRP with murine patellar tendon injury model, leading to future elucidation of the mechanisms of PRP on healing processes. Methods: Full-thickness defects were created in the central third of the murine patellar tendon. The prepared allogenic PRP gel was applied on the defect of the patellar tendon (PRP group), while the remaining mice served as the untreated control group. Mice were sacrificed at 2, 4, 6, 8, and 10 weeks after the operation, with histological sections obtained in each time point (n = 4 / time point / group). Semi-quantitative histological evaluation was performed in accordance with the Bonar score. The variables included in this scoring system were cell morphology, ground substance, collagen arrangement, and vascularity, with higher grades indicating worse tendon structures. In addition, the ratio of the collagen fibers to the entire tendon tissue (FT ratio) was measured using KS400 software as a quantitative histological evaluation. Results: The total Bonar score in the PRP group was significantly lower than in control group. With regard to the variables in the Bonar score, the vascularity score was significantly higher in the PRP group at 2 and 4 weeks, while the collagen arrangement score was significantly lower in the PRP group at 8 weeks. Based on a quantitative evaluation, the recovery speed of the patellar tendon determined by FT ratio was significantly faster in the PRP group than in the control group at 6 and 8 weeks. Conclusions: We have developed an experimental method for histological and quantitative evaluation of the effects of PRP on tissue healing using murine patellar tendon injury model. The results of this study suggest that the local application of PRP could enhance the tissue-healing process both directly through action on localized cells and indirectly through the recruitment of reparative cells through the blood flow. Further investigations will be needed to confirm the mechanisms of PRP in tissue-healing processes with the development of this experimental model. [ABSTRACT FROM AUTHOR]

Tailoring the surface of biomaterial scaffolds has been a key strategy to modulate the cellular interactions that are helpful for tissue healing process. In particular, nanotopological surfaces have been demonstrated to regulate diverse behaviors of stem cells, such as initial adhesion, spreading and lineage specification. Here, we tailor the surface of biopolymer nanofibers with carbon nanotubes (CNTs) to create a unique bi-modal nanoscale topography (500 nm nanofiber with 25 nm nanotubes) and report the performance in modulating diverse in vivo responses including inflammation, angiogenesis, and bone regeneration. When administered to a rat subcutaneous site, the CNT-coated nanofiber exhibited significantly reduced inflammatory signs (down-regulated pro-inflammatory cytokines and macrophages gathering). Moreover, the CNT-coated nanofibers showed substantially promoted angiogenic responses, with enhanced neoblood vessel formation and angiogenic marker expression. Such stimulated tissue healing events by the CNT interfacing were evidenced in a calvarium bone defect model. The in vivo bone regeneration of the CNT- coated nanofibers was significantly accelerated, with higher bone mineral density and up-regulated osteogenic signs (OPN, OCN, BMP2) of in vivo bone forming cells. The in vitro studies using MSCs could demonstrate accelerated adhesion and osteogenic differentiation and mineralization, supporting the osteo-promoting mechanism behind the in vivo bone forming event. These findings highlight that the CNTs interfacing of biopolymer nanofibers is highly effective in reducing inflammation, promoting angiogenesis, and driving adhesion and osteogenesis of MSCs, which eventually orchestrate to accelerate tissue healing and bone regeneration process. Here we demonstrate that the interfacing of biopolymer nanofibers with carbon nanotubes (CNTs) could modulate multiple interactions of cells and tissues that are ultimately helpful for the tissue healing and bone regeneration process. The CNT-coated scaffolds significantly reduced the pro-inflammatory signals while stimulating the angiogenic marker expressions. Furthermore, the CNT-coated scaffolds increased the bone matrix production of bone forming cells in vivo as well as accelerated the adhesion and osteogenic differentiation of MSCs in vitro. These collective findings highlight that the CNTs coated on the biopolymer nanofibers allow the creation of a promising platform for nanoscale engineering of biomaterial surface that can favor tissue healing and bone regeneration process, through a series of orchestrated events in anti-inflammation, pro-angiogenesis, and stem cell stimulation. Image, graphical abstract [ABSTRACT FROM AUTHOR]

The aim of this work is to describe the change of physical properties of the callus material with the use of the proposed mathematical model for callus remodeling. Callus tissue can be considered as a biomaterial where it's properties change over time due to the stimulated healing process. The proposed model is based on the mechanical stimulus theory. It is used to estimate the stress-stimulated change in the callus, Young's modulus, and the density in the case of a mandible fracture. Three healing loading programs are discussed and compared: optimal, intermittent, and intermittent with residual load. Here, the optimal loading program is understood as the in-time change of stimulating loads, which results in the shortest necessary healing time and, simultaneously, in the most uniform distribution of material density in the analyzed domain. The necessary healing time is a period after which the callus density (and hence the Young's modulus) reaches the desired value. The results of the study suggest a significant difference in the value of the callus maximal density between all three analyzed loading programs for a given healing time interval. The highest values of the density are obtained using the optimal loading program, however, all three programs provide satisfactory density distributions. The analytical results are compared with the callus density estimation based on the computer tomography (CT) medical data. [ABSTRACT FROM AUTHOR]

Background. Concentrated bone marrow-derived mesenchymal stem cells (concentrated bMSCs) are used to improve in-vivo healing, yet in-vivo studies do not describe the cellular components that constitute the concentrated bMSCs. If different concentrating systems create concentrated bMSCs with different cellular components this could affect in-vivo study results. This study sought to compare the cellular components of concentrated bMSCs from two different separating systems. Methods. Matched bone marrow (BM) and whole blood were commercially obtained. BM was divided, processed then the concentrated bMSCs were plated and analyzed for cellular concentrates, morphology, triplex, and proliferation assays. The two separation systems used were Angel (system 1) produced from Arthrex, Inc, Naples FL and Smart- Prep (system 2) produced from Harvest Technologies, Lakewood, CO. Time points used were 1, 4, 24, 48, 72 and 96 hours. Blinded observers were used to assess morphology of cells at the 24 hour time point. Results. System 1 had significantly more CFUs (p=.0035) and more nucleated cells (p=.0056). Proliferation was significantly increased for system 1 at time points 1, 24, 48, 72, and 96 hours (p<.001). Cellular viability was significantly increased for system 1 at time points 1, 24 and 48 hours (p<.05). Apoptosis was significantly increased for system 1 at time points 1, 4, 24, 48, 72, 96 hours (p<.05). Cytotoxicity was significantly increased for system 1 at time points 1, 4, 24, 48, 72, 96 hours (p<.001). Morphology of System 1's cells were more consistent of mesenchymal stem cells (MSCs) (Kappa=0.44). Conclusion. Systems that are used to create concentrated bMSCs create populations of concentrated bMSCs with different cellular properties. Future in-vivo studies involving this cell population should describe the cellular properties of the concentrated bMSCs. [ABSTRACT FROM AUTHOR]

Aim. The therapeutic potential of adipose-derived stem cell conditioned medium (ASC-CM) was studied in the rabbit model of critical limb ischemia (CLI). Methods. Rabbits received treatment with ASC-CM or placebo. Gastrocnemius muscle tissue was collected 35 days after ischemia induction. Ischemic changes were evaluated in hematoxylin-eosin stained tissues for early (necrotic lesions/granulation tissue) and late (fibrous scars) phases of tissue repair. The expression of proangiogenic miR-126 was also evaluated using in situ hybridization. The levels of cytokines, insulin, and C-peptide were measured in blood. Results. Early repair phases were observed more often in placebo-treated samples (45.5%) than in ASC-CM-treated ones (22.2%). However, the difference was not statistically significant. We demonstrated a statistically significant positive correlation between the early healing phases in tissue samples and C-peptide levels in peripheral blood. The expression of proangiogenic miR-126 was also shown in a number of structures in all phases of ischemic tissue healing. Conclusion. Based on our results, we believe that treatment with ASC-CM has the potential to accelerate the healing process in ischemic tissues in the rabbit model of CLI. The whole healing process was accompanied by miR-126 tissue expression. C-peptide could be used to monitor the course of the tissue healing process. [ABSTRACT FROM AUTHOR]

Coagulation, inflammation, and hyperplasia frequently restrict the effectiveness of cardiovascular stents. It is critical to modify stent surfaces to allow for in situ tissue healing. Interrelated coagulation and inflammation can impede endothelialization and are critical to the long-term performance of cardiovascular implants. This study proposes a relatively bio-inert "Anti-fouling plus" coating that is effective in anti-coagulation and anti-inflammation at the early stage of implantation and provides mild inflammatory responses during tissue remodeling process. The phosphorylcholine (PC)-based polymer PM(PCLA) is reacted onto a polydopamine-treated polylactic acid (PLA) surface. PC-based polymers that mimic cell membranes present remarkable antiinflammation and anticoagulation properties. The composite of epigallocatechin gallate (EGCG) and tempol is loaded on the PM(PCLA) coating to achieve "anti-fouling plus" which can mediate inflammatory responses by scavenging reactive oxygen species. In vitro hemocompatibility and cell tests demonstrate the effectiveness of coatings in inhibiting thrombus and inflammation. Interestingly, this study originally reveals a novel strategy that the anti-fouling plus coating can direct vascular tissue healing on stent via promoted endothelialization and mediated contractile smooth muscle cell phenotype by switching inflammatory cells to a pro-repair phenotype during tissue healing process, even if the coating is relatively bio-inert. An "Anti-fouling plus" coating combined with improved blood compatibility and enhanced inflammation-regulation ability can create a gentle microenvironment for neointima repair on the blood-contacting device surface, allowing for effective promotion of endothelialization as well as regulation of smooth muscle cell phenotypic transformation, and inflammatory cell transformation to a pro-repair type. [Display omitted] [ABSTRACT FROM AUTHOR]

Control over the implant surface functions is highly desirable to enhance tissue healing outcomes but has remained unexplored to adapt to the different service stages. In the present study, we develop a smart titanium surface by orchestrating thermoresponsive polymer and antimicrobial peptide to enable dynamic adaptation to the implantation stage, normal physiological stage and bacterial infection stage. The optimized surface inhibited bacterial adhesion and biofilm formation during surgical implantation, while promoted osteogenesis in the physiological stage. The further temperature increase driven by bacterial infection induced polymer chain collapse to expose antimicrobial peptides by rupturing bacterial membranes, as well as protect the adhered cells from the hostile environment of infection and abnormal temperature. The engineered surface could inhibit infection and promote tissue healing in rabbit subcutaneous and bone defect infection models. This strategy enables the possibility to create a versatile surface platform to balance bacteria/cell-biomaterial interactions at different service stages of implants that has not been achieved before. [Display omitted] [ABSTRACT FROM AUTHOR]

Background: Many factors contribute to uneventful and healthy postoperative healing. Hence, closure of periodontal flap postsurgery for the attainment of primary union between flap margins is of utmost importance. Isoamyl 2-cyanoacrylate is a tissue adhesive, which can be used for the closure of elevated flaps to overcome the problems associated with conventional suture material like silk. Aim: This study aims to compare healing after periodontal flap surgery using isoamyl 2-cyanoacrylate (bioadhesive material) and silk sutures. Materials and Methods: The study was carried out on twenty patients who needed flap surgical procedure for pocket therapy. Statistical Analysis Used: Results were subjected to statistical analysis. Paired t-test was used for intragroup postprocedure improvement in each parameter, and independent sample t-test was used for intergroup comparison. Results: Early healing was seen with isoamyl 2-cyanoacrylate during the 1st week when compared with silk. However, no significant difference was seen in the 2nd week when both the materials were compared. Conclusions: It can be concluded that cyanoacrylate aids in early initial healing.

To reduce and prevent postsurgical adhesions, a variety of scientific approaches have been suggested and applied. This includes the use of advanced therapies like tissue-engineered (TE) biomaterials and scaffolds. Currently, biocompatible antiadhesive constructs play a pivotal role in managing postoperative adhesions and several biopolymer-based products, namely hyaluronic acid (HA) and polyethylene glycol (PEG), are available on the market in different forms (e.g., sprays, hydrogels). TE polymeric constructs are usually associated with critical limitations like poor biocompatibility and mechanical properties. Hence, biocompatible nanocomposites have emerged as an advanced therapy for postoperative adhesion treatment, with hydrogels and electrospun nanofibers among the most utilized antiadhesive nanocomposites for in vitro and in vivo experiments. Recent studies have revealed that nanocomposites can be engineered to generate smart three-dimensional (3D) scaffolds that can respond to different stimuli, such as pH changes. Additionally, nanocomposites can act as multifunctional materials for the prevention of adhesions and bacterial infections, as well as tissue healing acceleration. Still, more research is needed to reveal the clinical potential of nanocomposite constructs and the possible success of nanocomposite-based products in the biomedical market.

Enteric fistula (EF), a serious complication after abdominal surgery, refers to unnatural communication between the gastrointestinal tract and the skin or other hollow organs. It is associated with infection, massive fluid/electrolyte loss, and malnutrition, resulting in an unhealed course. Despite advances in surgical techniques, wound care, infection control, and nutritional support, EF remains associated with considerable morbidity and mortality. Autologous platelet-rich plasma (PRP) containing elevated platelet concentrations has been proposed to promote healing in many tissues. However, the mechanism of action of PRP in EF treatment remains unclear owing to its complicated clinical manifestations. In this review, we summarized the clinical approaches, outlined the principal cytokines involved in the healing effects, and discussed the advantages of PRP for EF therapy. In addition, we defined the mechanism of autologous PRP in EF management, which is essential for further developing EF therapies., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Liang, Zheng, Li, Yang, Qin, Zhao, Wang and Wang.)

The application of traditional materials to tissue healing in sports rehabilitation training has problems such as poor effect, high rejection reaction, and slow healing speed. It also brings many challenges to the development of sports rehabilitation training. This article aims to explore the impact of composite conjugated materials on tissue healing to promote rapid and efficient tissue healing and improve the effect of sports rehabilitation training. Through research and analysis, this article found that composite conjugated materials have unique biocompatibility and can promote cell growth and differentiation. In skin tissue healing, composite conjugated materials can control the release rate and duration of drugs to promote skin healing. During the fracture healing process, conjugated materials can provide growth factors and extracellular matrix components, stimulate bone cell proliferation and differentiation, and promote fracture healing. In terms of soft tissue injuries, composite conjugated materials serve as supporting structures or matrices, providing a favorable environment for the regeneration of damaged tissue. In the regulation of inflammatory responses, composite conjugated materials reduce inflammatory responses and accelerate the healing process by modulating immune responses. The results of this study show that 1 week after the experiment, the skin healing rates of the control group and the experimental group were 42.55% and 58.17% respectively; 5 weeks after the experiment, the skin healing rates of the control group and the experimental group were 51.28% and 73.24% respectively. After 1, 2, 3, 4, and 5 weeks of experiment, it was found that the average tissue repair rates of the control group were 44.03%, 54.18%, 58.40%, 67.08%, and 72.09% respectively, and the average tissue repair rates of the experimental group were 52.18%, 61.91%, 63.40%, 74.61%, and 85.05% respectively. This study highlights the huge potential of composite conjugated materials in promoting tissue healing and tissue repair, and is of great significance for promoting technological progress in the field of sports rehabilitation and improving rehabilitation effects., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Li and Zhang.)