Search Results (515)

Background/Objectives: Mesenchymal stem cells (MSCs), due to their regenerative and multipotent properties, have emerged as promising therapeutic agents in tissue repair and regeneration. These biological characteristics might contribute to optimized anastomotic healing and to a reduction in postoperative complications following digestive surgery. The present study aimed to evaluate whether intraperitoneal or perianastomotic administration of MSCs provides superior healing outcomes in colonic anastomoses in Wistar rats. Methods: MSCs were isolated from inguinal adipose tissue harvested from 2 Wistar rats. Thirty male Wistar rats were allocated to 3 groups: (i) the control group, with regular anastomosis, (ii) peri-anastomotic injection of MSCs, and (iii) intraperitoneal injection of MSCs. The animals were sacrificed on postoperative day 14. The evaluated outcomes included clinical evolution, adhesion index, histological characteristics, and tissue hydroxyproline content. Results: The incidence of anastomotic leakage and the mortality rate were 0%. Therefore, the present study primarily demonstrates changes in surrogate markers of healing, including inflammatory response, collagen deposition, adhesion formation, and hydroxyproline content. The adhesion index was similar in the groups receiving MSC administration (p = 0.05); however, intraperitoneal administration demonstrated superior outcomes when compared to standard anastomosis in reducing adhesion formation (p = 0.002). Histopathological analysis showed a decreased inflammatory process and an increased collagen deposition at the anastomotic site following MSC administration (p < 0.05). Moreover, tissue hydroxyproline levels were significantly increased after both perianastomotic (0.831 ± 0.02, p < 0.05) and intraperitoneal (0.54 ± 0.02, p < 0.05) MSC administration compared with the control group (0.251 ± 0.006). Conclusions: These results suggest that MSC administration may improve histological and biochemical markers associated with colonic anastomotic healing in a non-ischemic experimental model. The experimental model used is suitable for further studies aimed at determining the optimal indications, routes of administration, and adjunctive agents that may potentiate the effects of MSCs. Full article

Background: Periorbital aging involves complex structural and functional changes, including decreased eyelid opening and alterations in infraorbital contour. Conventional collagen biostimulators mainly focus on localized volume augmentation and dermal remodeling, with limited considerations for broader tissue interactions within the periorbital region. Objective: To evaluate structural and functional changes following treatment with a liquid-type polycaprolactone (PCL)-based collagen biostimulator. Methods: Three patients were analyzed. Clinical photographs were obtained at baseline, 1 month, and 3 months. Measurements were normalized to iris diameter. Eyelid-related and infraorbital contour parameters, along with canthal tilt angle (CTA), were assessed under neutral gaze and maximal effort. The treatment was performed via upper (forehead) and lower (infraorbital) approaches without direct injection into the upper eyelid. Results: Margin reflex distance 1 (MRD1) showed an overall increasing trend in both neutral gaze and maximal effort conditions, while ΔMRD1 remained relatively unchanged. Medial canthus-to-brow vertical distance (CBVD-M) showed a tendency to increase, whereas brow-to-lid distance (BLD) and lateral CBVD (CBVD-L) did not demonstrate consistent patterns. CTA increased across cases. Upper concavity height (UC), peak protrusion height (PP) and lower concavity height (LC) decreased concurrently. Conclusions: Liquid-type PCL-based treatment was associated with functional and structural changes in the periorbital region. Improved eyelid opening without direct upper eyelid injection may suggest indirect regional effects through contiguous anatomical planes. Changes in lower eyelid contour parameters support broader structural and functional changes. Full article

Dermal senescence is associated with reduced fibroblast activity, decreased extracellular matrix synthesis, and impaired tissue repair. Commercial injectable formulations containing poly-L-lactic acid (PLLA), hyaluronic acid (HA), and polydeoxyribonucleotide (PDRN)-associated compounds have been proposed for dermal remodeling approaches and modulate tissue-response pathways; however, comparative studies evaluating commercially available formulations under standardized experimental conditions remain limited. This study aimed to characterize the morphology of formulations containing PLLA, HA, and PDRN, used alone or in combination, by environmental scanning electron microscopy (ESEM), and to investigate formulation-associated histological and collagen-related molecular responses in a murine model. Formulations containing PLLA, HA, HA + PDRN, and PLLA, HA and PDRN were administered into the dorsal subcutaneous tissue of 14 Mus musculus mice (Swiss strain). After 30 days, tissue response was assessed by ultrasound, histological analysis with Masson’s trichrome staining, and RT-qPCR quantification of collagen-related gene expression. ESEM analysis revealed distinct morphological characteristics among the biomaterials, and the combined PLLA, HA and PDRN formulation exhibited a more complex and integrated multiphase structure. Histological analysis showed preserved tissue architecture in all groups, with no evidence of marked inflammatory response or structural disruption. RT-qPCR demonstrated significantly higher COL1A1 expression in the PLLA-only and PLLA, HA, and PDRN groups compared with controls (p < 0.05), whereas no significant differences were observed for COL2A1 or COL3A1. These findings indicate that PLLA-containing formulations were associated with selective COL1A1 upregulation under the evaluated conditions, suggesting formulation-associated collagen-related molecular responses in this short-term model. Full article

Introduction: Chronic wounds and pathologic scars remain a persistent challenge in plastic surgery. Conventional treatments can be costly and inconsistent, prompting interest in regenerative approaches that utilize autologous tissue. Emulsified fat produces nanofat through mechanical processing and contains adipose-derived stem cells, stromal vascular fractions, extracellular matrix proteins, cytokines and growth factors. The purpose of this systematic review is to evaluate the use of autologous nanofat for wound healing and scar management, with emphasis on preparation techniques, treatment indications, and outcomes. Methods: A comprehensive PubMed search with no date restrictions was conducted in January 2026 using MeSH terms and keywords related to nanofat and wound-healing applications. Studies were screened independently by two reviewers using the Rayyan platform. Eligible studies evaluated nanofat for wound healing in human or animal subjects; non-English articles, studies not involving nanofat, editorials, and conference abstracts were excluded. The extracted data included study characteristics, participant numbers, treatment details, indications, adjunct therapies, follow-up duration, outcomes, and complications. Studies were grouped by clinical application, with individual reports included in multiple categories when relevant. Results: The search identified 53 records, of which 22 studies met the inclusion criteria after screening. These included 20 human and two animal studies spanning randomized controlled trials (n = 3), prospective trials (n = 6), retrospective analyses (n = 6), case series (n = 4), and case reports (n = 3). Mechanical emulsification was the predominant autologous nanofat preparation method (91%), often combined with filtration or centrifugation. Clinical indications in human studies were diverse, most commonly including scar treatment (n = 14) (acne, burns, depressed, and post-surgical), followed by chronic wounds (n = 3) and reconstructive applications (n = 3). Nanofat was administered via injection in 86% of studies (n = 19), typically using fine-gauge needles or microcannulas with intradermal or subdermal placement, while three studies used non-injection approaches such as topical, membrane, or dressing-based delivery. Scar or aesthetic parameters, measured using VSS, POSAS, physician grading, photography, pigmentation analysis, or clinical appearance, were evaluated in 73% of studies (n = 16), and all reported improvement in variables such as pigmentation, pliability, thickness, texture, or overall appearance. Wound-healing endpoints were assessed in 36% (n = 8), with 100% (n = 8) demonstrating accelerated healing, improved epithelialization, or defect closure. Patient-reported outcomes, including satisfaction or quality of life, were measured in 32% (n = 7), and all showed improvement. Objective imaging modalities (e.g., 3D imaging, ultrasound, angiography, digital analysis) were used in 23% (n = 5), each confirming structural or physiologic improvement. Histologic or biomolecular analyses were performed in 27% (n = 6) and uniformly demonstrated regenerative changes, such as increased angiogenesis, collagen remodeling, or growth factor expression. Treatment was well tolerated, with 77% of studies (n = 17) reporting minimal or no complications and only transient mild adverse effects, including mild pain, bruising, erythema, and edema. Conclusions: Current evidence suggests that autologous nanofat is a promising regenerative therapy for wound healing and scar modulation. Across diverse clinical applications, nanofat has been associated with improved tissue quality, enhanced healing, and favorable patient-reported outcomes, with minimal complications. The mechanical processing of autologous tissue may also involve fewer regulatory concerns compared with more extensively manipulated cellular products. Full article

Current treatments for choroidal neovascularization (CNV) and its associated subretinal fibrosis (SRF), major causes of vision loss, are limited by the need for frequent intravitreal injections and the emergence of drug resistance. This study evaluated the safety and efficacy of the intravitreal administration of engineered humanized anti-vascular endothelial growth factor Nanobodies, including a wild-type Nanobody (WHNb) and two mutated variants (MHNb136 and MHNb256), in a rat model of laser-induced CNV and associated SRF. Safety was assessed through in vivo electrophysiological and histopathological analyses following intravitreal injection of Nanobodies at doses of 12.5, 25, 50, and 100 µg. Efficacy was evaluated in rat models of laser-induced CNV and SRF using double immunohistochemistry for isolectin B4 and anti-collagen type I on sclerochoroidal flat mounts. Mean CNV and SRF areas in Nanobody-treated groups were compared with those in bevacizumab-treated and sham control groups. None of the Nanobodies showed retinal toxicity in safety assessments. Compared with bevacizumab, MHNb136 and MHNb256 reduced the CNV area by 1.72-fold and 1.8-fold, respectively (both p < 0.0001), whereas WHNb showed an effect nearly identical to that of bevacizumab. In addition, 12.5 µg MHNb136 and 100 µg MHNb256 reduced the SRF area by 1.3-fold (p = 0.047) and 1.6-fold (p = 0.0007), respectively, relative to bevacizumab. For CNV reduction, 12.5 µg MHNb136 was comparable to 25 µg MHNb256; both outperformed bevacizumab. For SRF reduction, 12.5 µg MHNb136 was more effective than bevacizumab and comparable to 100 µg MHNb256. These findings suggest that 12.5 µg MHNb136 may represent a cost-effective bioengineered Nanobody candidate for future clinical studies. Full article

Aesthetic medicine is shifting from symptomatic correction to biological structural restoration. Regenerative aesthetics represents a frontier in dermatology, focusing on the restoration of the skin microenvironment to enhance cellular vitality and tissue resilience. Central to this approach is the concept of “skin bed preparation”, a strategic priming phase designed to optimize the physiological terrain before the delivery of advanced aesthetic interventions. This review explores the molecular and cellular mechanisms by which skin bed preparation modulates the extracellular matrix (ECM) and the dermal niche to maximize the efficacy of subsequent treatments and promote long-term skin longevity. Evidence suggests that biostimulatory priming utilizing senolytics, senomorphics, mitochondrial, and/or epigenetic rejuvenators rehabilitates the fibroblast–collagen interactome. By reducing oxidative stress and chronic low-grade inflammation, these preparatory steps transition the skin from a catabolic to an anabolic state. This metabolic reset ensures that subsequent procedures, such as laser therapy, injectable fillers, encounter a responsive cellular environment, resulting in superior collagen induction and prolonged clinical outcomes. Optimizing the skin microenvironment via regenerative aesthetics is not merely an adjunctive step but a fundamental requirement for therapeutic success. Integrating skin bed preparation into clinical protocols provides a synergistic framework that enhances immediate procedural results while addressing the underlying hallmarks of skin aging, ultimately redefining the trajectory of skin health and longevity. Full article

This study aimed to develop antibacterial polyphenol–chitosan hydrogel dressings and, more importantly, to compare how three structurally distinct low-cost natural polyphenols—protocatechuic acid (PCA), gallic acid (GA), and tannic acid (TA)—regulate hydrogel performance within the same chitosan platform. PCA, GA, and TA were incorporated into chitosan to obtain the corresponding hydrogels, denoted CS-PCA, CS-GA, and CS-TA. Scanning electron microscopy confirmed that all formulations possessed a three-dimensional porous network. Rheological characterization revealed favorable viscoelastic behavior for all polyphenol-containing hydrogels, with CS-TA showing the highest mechanical strength in the present system. The hydrogels also exhibited pH-responsive swelling, good tissue adhesion, self-healing ability, and injectability. In vitro antibacterial assays demonstrated activity against both Gram-positive and Gram-negative microorganisms, with CS-TA showing the most favorable overall antibacterial performance under the tested conditions. In a rat full-thickness wound model, hydrogel treatment accelerated wound closure, while H&E staining indicated enhanced granulation tissue formation, collagen deposition, and reduced inflammatory cell infiltration. Collectively, these findings support the use of polyphenol–chitosan composite hydrogels as promising wound-dressing candidates and highlight the value of a side-by-side comparison of PCA, GA, and TA for understanding structure–property–function relationships in this class of materials. Full article

Objective: In this study, Dehydroepiandrosterone (DHEA-induced Polycystic Ovary Syndrome (PCOS) mice were used as models to evaluate the improvement effect of Vitexin (Vit) on ovarian fibrosis and explore the mechanism of action of the NR4A1/NLRP3 signaling pathway. Method: Sixty 4-week-old female ICR mice of the same batch number were selected and their systems were divided into 6 groups (n = 10): normal (Control, Ctrl) group, model (Polycystic Ovary Syndrome, PCOS) group, treatment (Vitexin, The Vit group, normal NR4A1 gene silencing group (Ctrl NR4A1^-/-), NR4A1 gene silencing model group (PCOS NR4A1^-/-), and NR4A1 gene silencing treatment group (Vit NR4A1^-/-). Silencing gene modeling was performed by tail vein injection of adeno-associated virus (serotype AAV-8), and the mouse genotypes were detected by qRT-PCR technology 14 days after injection. After the genotype was determined, the PCOS group and the PCOS NR4A1^-/- group were administered dehydroepandrosterone (6 mg/100 g/d) by gavage for 28 consecutive days for modeling, while the Vit group and the Vit NR4A1^-/- group were treated with dehydroepandrosterone + vitexin (10 mg/kg/d) by gavage for 28 consecutive days. All mice were raised with pure water and regular maintenance food. After 4 weeks of drug intervention, the mice were euthanized and samples were collected. The pathological changes in ovarian tissue were observed by H&E staining, and the degree of ovarian tissue fibrosis was observed by Masson staining. The levels of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px), malondialdehyde (MDA), total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) in mouse serum were detected by biochemical kits. The levels of inflammatory factors (IL-1β, IL-6, IL-18, TNF-α) in mouse serum were determined by enzyme-linked immunosorbent assay. Real-time fluorescence quantitative PCR (qRT-PCR) was used to detect oxidative kinase (Gsta4, Prdx3, Mgst1, Gpx3, Gsr), inflammatory factors (Nlrp3, Caspase-1, Asc, Il-1β, Il-18, Tnf-α) and fibrotic pathway-related genes (Tgf-β1, Smad3, Collagen1, CTGF, α-SMA, Mmp-13, and β-catenin) in ovarian tissues. The levels of inflammatory factors (NLRP3, Caspase-1, ASC, IL-1β, IL-18, TNF-α, IκBα) and fibrosis in mice were determined by Western blot method, and statistical description and analysis were performed using SPSS software. Result: In the wild-type genotype group, compared with the PCOS group, Vit treatment could effectively regulate the metabolic abnormalities of PCOS mice, including inhibiting excessive weight gain, restoring normal glucose tolerance, and reducing body fat content. After Vit treatment, the levels of MDA, TC, TG, LDL, IL-1β, IL-6, IL-18 and TNF-α in the serum of PCOS mice were significantly reduced, while the levels of SOD and HDL in the serum of PCOS mice were increased. The staining results indicated that Vit treatment could significantly inhibit the process of ovarian fibrosis in PCOS mice. The results of WB and PCR demonstrated that after Vit gavage treatment in mice, inflammatory and fibrotic factors such as Nlrp3, Caspase-1, Asc, Il-1β, Il-18, Tgf-β1, Smad3, Collagen1, CTGF, and α-SMA in ovarian tissues could be significantly down-regulated, and the fibrotic level of ovarian tissues could be reduced. Among the same measurement indicators, the silenced NR4A1 group showed a certain degree of increase compared with the wild genotype group, but there was no significant difference. Conclusions: Vit intervention can restore the sex hormone levels and follicular development in ovarian tissues of PCOS mice, regulate reproductive endocrine disorders and abnormal lipid metabolism levels, and regulate the expression of Collagen I, a-SMA and CTGF in the ovaries by inhibiting the NR4A1/NLRP3 signaling pathway, thereby improving the ovarian fibrosis level of PCOS mice. It is suggested that it may play a key role in the treatment of PCOS and the prevention and delay of its long-term complications. Full article

Objectives: This study aimed to investigate the therapeutic efficacy of a hydrogel loaded with Wharton’s Jelly mesenchymal stem cells (WJ-MSCs) and melatonin, administered to the liver either via mesh–hydrogel implantation or intraperitoneal hydrogel injection, in a thioacetamide (TAA)-induced liver fibrosis animal model. Methods: A collagen-based hydrogel containing WJ-MSCs and melatonin was prepared for injection as well as combined with electrospun mesh for implantation. Hydrogel and mesh were characterized with respect to morphology, degradation, and mechanical properties. In in vivo studies, liver fibrosis was induced in rats by intraperitoneal injection of TAA for 6 weeks. After fibrosis induction, animals received either hydrogel injection or implantation of the combined construct. After 21 days, serum and liver tissues were collected, and biochemical, histopathological, and ultrastructural analyses were performed through comparative evaluation of experimental groups. Results: SEM results demonstrated that hydrogel, with appropriate porosity, was well integrated with the mesh without any detachment. The mesh, composed of submicron-scale fibers, exhibited a Young’s modulus of 10.37 ± 2.33 MPa. The hydrogel presented a degradation profile with a 40% mass loss in 24 h, reaching approximately 50% by day 30. Biochemical results indicated significant improvement in liver regeneration with both treatment strategies, particularly with the implanted construct. Histopathological analysis revealed decreased inflammation and hepatocyte vacuolization following both treatments; however, collagen accumulation was significantly reduced in the implant group. Ultrastructural analysis showed preserved nuclear integrity and reduced endoplasmic reticulum dilation and degenerative changes in implant group. Conclusions: The combination of WJ-MSCs and melatonin-loaded hydrogel with supportive mesh particularly enhanced tissue regeneration in liver fibrosis. Full article

Background/Objective: Myocardial fibrosis (MF) is a prevalent pathological endpoint in various heart diseases, characterized by extracellular matrix (ECM) dysregulation and oxidative stress. Hyperoside (Hyp) plays a role in regulating cardiac oxidative stress and fibrosis. This study aimed to elucidate whether Hyp regulates isoproterenol (ISO)-induced MF in mice by modulating the GATA4/HIF-1α signaling pathway and reducing oxidative stress. Methods: The binding affinity of Hyp to GATA4 and HIF-1α was assessed through molecular docking and dynamics simulation. The MF model of mice was established by subcutaneous injection of ISO. Cardiac function was measured by echocardiography. Myocardial injury and collagen deposition were examined using H&E and Sirius red staining. Levels of fibrosis markers, oxidative stress indicators, and GATA4/HIF-1α pathway indicators in serum and heart tissue were quantified by ELISA, Western blot, RT-qPCR and flow cytometry. The distribution of myocardial marker proteins was visualized by immunofluorescence and immunohistochemistry. Results: Molecular docking revealed high binding affinity of Hyp to GATA4 and HIF-1α (binding energies < −5.0 kcal·mol⁻¹), and dynamics simulation showed that the complex’s structure remained stable over 100 nanoseconds (RMSD < 0.1 nm). High-dose Hyp (36 mg/kg) significantly improved cardiac function, myocardial injury, collagen deposition, and inflammatory infiltration in MF mice. Molecularly, Hyp effectively reduces oxidative stress and fibrosis through upregulating GATA4 and downregulating HIF-1α. Conclusions: Hyp suppresses oxidative stress by activating the GATA4/HIF-1α pathway, presenting a promising therapeutic target for the treatment of MF. Full article

A recently identified mesenchymal cell population, telocytes (TCs), has been found in many tissues of different animal species. Jet needle-free injection (JNFI) is a promising non-invasive drug-delivery method that can trigger effective immune responses in the skin. In this preliminary morphological study, an inactivated porcine circovirus vaccine was delivered into pig neck skin by JNFI, and untreated normal neck skin served as the control. Histopathology, immunohistochemistry (IHC), immunofluorescence (IF), and transmission electron microscopy (TEM) were used to evaluate TC distribution, ultrastructure, and selected quantitative TEM parameters 24 h after injection. TCs were widely distributed in porcine skin, located between collagen fibers and around blood vessels, adipocytes, and sweat glands. They were also observed in contact with mast cells. TCs around sweat glands were CD34⁺, Vimentin⁺, and α-SMA⁺, whereas TCs at other sites were CD34⁺, Vimentin⁺, and α-SMA⁻. After JNFI, inflammatory cell infiltration into the skin was observed; TCs were in contact with these cells, and TCs surrounding adipocytes redistributed into the adjacent loose connective tissue. Quantitative TEM analysis showed that TC profile density and visible telopod length did not differ significantly between normal skin and JNFI 24 h skin (p ≥ 0.05). In contrast, vesicle profiles per TC increased significantly in both perivascular and adipose-associated compartments (p < 0.05). These findings provide morphological evidence suggesting that TCs may participate in early cutaneous responses after JNFI vaccine delivery. Full article

Background and Objectives: Keloids are fibroproliferative disorders marked by excessive fibroblast activity, abnormal collagen deposition, and impaired wound healing. They are frequently associated with pain, pruritus, and significant aesthetic concerns, leading to reduced quality of life. Surgical excision alone is burdened by high recurrence rates, underscoring the need for effective adjuvant therapies. This systematic review aimed to assess the effectiveness of surgical excision combined with adjuvant physical and pharmacological therapies in keloid management, with particular emphasis on recurrence rates. Materials and Methods: The review was conducted in accordance with PRISMA guidelines. A systematic search of PubMed and Web of Science identified studies evaluating surgical excision of keloids with adjunctive therapies. Twenty-one studies involving more than 8627 patients met the inclusion criteria. Extracted data included study design, patient and lesion characteristics, treatment modalities, and recurrence rates. Due to marked heterogeneity among treatment protocols, a meta-analysis was not performed. Results: Among physical adjuvant therapies, postoperative brachytherapy showed the lowest recurrence rates (3.1–15%), outperforming radiotherapy and external-beam radiation therapy (14–29.3%). Compression therapy achieved recurrence rates of 10.66% and 14%, particularly effective in auricular keloids. Pharmacological adjuvant therapies demonstrated variable efficacy. Triamcinolone acetonide injections were associated with recurrence rates ranging from 6.6% to 33%, depending on the protocol. Adjuvant 5-fluorouracil reduced recurrence compared with surgery alone, whereas imiquimod 5% showed higher and less consistent recurrence rates. Combination pharmacological therapies consistently yielded better outcomes than monotherapy. Conclusions: Surgical excision combined with adjuvant therapy is the most effective strategy for keloid treatment. Multimodal approaches significantly reduce recurrence compared with surgery alone. However, substantial heterogeneity in lesion characteristics, treatment timing, and therapeutic protocols limits comparability between studies. Further high-quality, standardised clinical trials are needed to optimise management strategies and develop evidence-based guidelines. Full article

Polystyrene nanoparticles (PS-NPs) present significant risks to respiratory health, contributing to lung fibrosis. Current therapeutic strategies for PS-NP exposure injuries are limited and often ineffective. One promising solution is immunological training. This study explores the novel role of Candida albicans in immune training to alleviate PS-NP-induced fibrosis. Our findings demonstrate that C. albicans enhances immune responses in a unique way, advancing current frameworks of trained immunity and offering new therapeutic approaches for health issues related to environmental pollutants. We conducted experiments using male BALB/c mice exposed to 80 nm PS-NPs via posterior pharyngeal drip. Prior to exposure, the mice received an intravenous injection of low-dose C. albicans to induce immunological training. To evaluate the protective effects of C. albicans, we assessed survival rates, pulmonary histopathology, and gene expression profiles. The results indicated that while 100% of the control group exposed to PS-NPs did not survive, the group pre-treated with C. albicans exhibited complete survival. Histopathological analysis revealed preserved lung architecture and a significant reduction in collagen deposition in the C. albicans + PS-NPs group compared to the PS-NPs only group. Additionally, RNA sequencing analysis identified a total of 415 differentially expressed genes, including five upregulated circadian rhythm genes (Per3: 1.93-fold, Rorc: 1.69-fold, Cry1: 2.01-fold, Per1: 2.55-fold, Per2: 2.73-fold) and one downregulated circadian rhythm gene (Npas2: 0.42-fold) in the C. albicans + PS-NPs group compared to the PS-NPs group. C. albicans-based immune training reduces lung fibrosis and enhances survival after PS-NP exposure, suggesting a promising therapeutic strategy. Full article

Regenerative medicine aims to restore the structure and function for improved tissue health; reduced tissue health can arise from causes such as aging, which results in the ongoing degradation of the extracellular matrix (ECM) of the skin. Replacement of a single biological component is not sufficient for an esthetic treatment to be described as regenerative; it is the relative amounts, ratios, types and organization of stimulated components that are important in a treatment’s regenerative potential. Regenerative aesthetics aims to recapture the youthful structure and function of tissue by exploiting the body’s own systems. Poly-L-lactic acid (PLLA-SCA; Sculptra^®), an injectable, biodegradable, non-permanent biostimulator, induces a combination of mechanotransductional/mechanical stimulation and foreign body reaction response and promotes ECM remodeling via the production of collagen through the upregulation of cytokines interleukin-1b and CXCL6, elastin, proteoglycans and multiadhesive glycoproteins. In addition, PLLA-SCA stimulates adipocyte rejuvenation/adipogenesis and increases the thickness of the dermis and adipose layers. Hence, PLLA-SCA stimulates endogenous pathways, and the array of biostimulatory effects should not be considered individually but as interlinked with the overall goal of improvement in skin health. These effects manifest clinically as long-term improvements in the mechanical properties of the skin, the restoration of volume and elasticity, improvements in skin quality and thickness, and dermal remodeling. Full article

Background: With the increasing demand for non-surgical facial rejuvenation, injectable collagen biostimulators such as poly-L-lactic acid (PLLA), calcium hydroxyapatite (CaHA), polycaprolactone (PCL), poly-D,L-lactic acid (PDLLA) and powdered polydioxanone (PPDO) have become widely used by facial aesthetic practitioners. These agents stimulate neocollagenesis, providing gradual improvement in skin firmness, elasticity and facial contour with long-lasting results. While manufacturers emphasize the efficacy and favorable safety profile of these products, adverse events such as nodules, edema, inflammatory reactions and, in rare cases, granulomas have been reported. To date, no comprehensive systematic review has evaluated the proportion and nature of adverse effects associated with all major collagen biostimulators in facial aesthetic procedures. This study aims to synthesize current evidence on the proportion of adverse events linked to injectable collagen biostimulators. Methods: The systematic review will include clinical studies involving adults undergoing facial aesthetic procedures with PLLA, PDLLA, CaHA, PCL and PPDO that report adverse events during or after treatment. The search will be conducted in six main databases: CENTRAL, EMBASE, LILACS, PubMed, SCOPUS and Web of Science. No restrictions will be applied regarding language or publication date. The screening process will occur in two phases: first, two independent reviewers will assess titles and abstracts against the eligibility criteria; second, the same reviewers will conduct full-text evaluations. Data will be synthesized narratively, with a meta-analysis of proportions performed if appropriate. Additionally, sample characteristics, treatment protocols, study design and main findings will be reported. The risk of bias will be assessed independently by two reviewers using appropriate tools, based on the study design, with the support of artificial intelligence. PROSPERO registration number: CRD420251062785. Full article