Search Results (18)

Despite advances in periodontal regenerative therapies, consistent tissue regeneration remains challenging, with cells playing an essential role in successful repair. Therefore, this study tested different dental bone substitutes embedded in the chorioallantoic membrane (CAM) combined with periosteum-derived micrografts obtained using a chair-side device (Rigenera HBW system). Cell populations within the micrografts were identified and characterised via immunofluorescence and flow cytometry (CD31, CD105, CD34, CD90, CD73, and CD45). A CAM model was employed to examine the angiogenic potential of micrografts combined with bone substitutes, which were analysed through quantitative blood vessel/vascularisation assessments using the Ikosa software (2025), along with histological and immunohistochemical evaluations such as smooth muscle actin (SMA), H&E, and Masson’s trichrome staining. Statistical analysis was performed using GraphPad Prism 10. The addition of periosteum-derived micrografts resulted in angiogenic enhancement compared to the controls. Notable enhancement of total vessel area, total length, and branching points were obtained when Fisiograft^® (p = 0.0007, p = 0.0002, and p < 0.0001, respectively), New Shore^® (p = 0.0006, p = 0.0149, and p = 0.0083, respectively), and Bio-Oss^® (p = 0.0038 and p = 0.0010, respectively) were combined with micrografts, compared to the positive controls. The histological and immunohistochemical analyses confirmed increased vascularisation (positive staining for SMA) in the micrograft groups. Periosteum-derived micrografts represent a promising adjunct to conventional bone-grafting materials, promoting vascularisation and potentially enhancing tissue regeneration and healing outcomes. Full article

Background/Objectives: Chronic lower limb ulcers represent a significant clinical challenge, with conventional therapies achieving healing in only 30–40% of complex cases. This study evaluated the comparative effectiveness of autologous blood clot therapy (ActiGraft, delivering platelet- and leukocyte-derived growth factors) and autologous micrograft therapy (Rigenera, containing viable progenitor cells) versus advanced wound dressings for refractory chronic wounds. Methods: This retrospective analysis of a prospectively collected, non-randomized clinical cohort included 132 patients with chronic lower limb ulcers refractory to prior therapy, who were treated between 2019 and 2024 at a single wound care center. The patients received ActiGraft (n = 32), Rigenera (n = 33), or advanced wound dressings (n = 67) based on their choice after informed discussion. The primary outcome was complete wound closure at 52 weeks. Multivariable Poisson regression with robust variance was performed, adjusting for baseline wound area (log-transformed), chronic renal failure, age, and peripheral vascular disease. Cox proportional hazards was used to model time to closure. Bonferroni correction (threshold p < 0.0167) was applied for three pairwise comparisons. This study was not pre-registered, and the results should be considered hypothesis-generating. Results: Unadjusted wound closure rates were 68.8% (ActiGraft; RR = 1.71, 95% CI: 1.17–2.48, p = 0.015), 60.6% (Rigenera; RR = 1.50, 95% CI: 1.01–2.25, p = 0.089), and 40.3% (advanced dressings). After multivariable adjustment, ActiGraft showed attenuated benefit (adjusted RR = 1.38, 95% CI: 0.86–2.21, p = 0.179), while the beneficial effect of Rigenera became non-significant (adjusted RR = 1.19, 95% CI: 0.73–1.94, p = 0.488). However, the adjusted Cox regression revealed significantly faster healing for ActiGraft (HR = 10.67, 95% CI: 4.17–27.30, p < 0.001) and Rigenera (HR = 4.12, 95% CI: 1.75–9.73, p = 0.001). Sensitivity analyses restricted to comparable wound sizes (≤10 cm²) showed a consistent direction of effect (ActiGraft 71.4% vs. Advanced 37.5%). Infection rates were lower in the autologous therapy groups (0–3.0% vs. 11.9%; Fisher’s exact p = 0.006). Conclusions: ActiGraft autologous blood clot therapy showed trends toward superior wound closure and demonstrated significantly faster healing compared to advanced dressings in patients with refractory chronic lower limb ulcers, with autologous micrograft therapy (Rigenera) showing intermediate results. Significant baseline imbalances in wound size limit causal inference from the closure rate comparisons. These hypothesis-generating findings from a non-randomized cohort warrant confirmation in adequately powered randomized controlled trials with stratification by wound characteristics. Full article

Androgenetic alopecia (AGA) is a prevalent, multifactorial hair disorder affecting a substantial portion of both males and females, with significant psychosocial consequences. Over the past decade, regenerative medicine has reshaped AGA treatment, offering biologically driven alternatives to conventional pharmacological and surgical therapies. Among these, Autologous Micrografting Technology (AMT) (Regenera Activa^® by Rigenera^® Technology, Barcelona, Spain) emerged 10 years ago as a notable innovation leveraging the body’s intrinsic regenerative potential through micrografts derived from a healthy scalp tissue. This review provides a comprehensive overview of the pathophysiology of AGA—including genetic, hormonal, and inflammatory contributors—and evaluates the clinical efficacy, safety, and mechanistic basis of AMT in comparison with other regenerative strategies such as platelet-rich plasma, adipose-derived mesenchymal stem cells, and exosome-based treatments. Clinical studies demonstrate that AMT yields significant short-term improvements in hair density and thickness with favorable safety outcomes. Moreover, advancements in device technology and treatment protocols have enhanced consistency and reproducibility. As multimodal and personalized approaches gain traction in hair restoration, AMT is a minimally invasive point-of-care procedure within the evolving regenerative landscape. Future studies are warranted to optimize treatment algorithms, extend follow-up data, better define patient selection criteria for maximizing outcomes with AMT, and expand the indication of autologous micrografting technology. Full article

Adipose tissue micrografts (ATM) and dermis micrografts (DMG) have emerged as promising autologous therapies in regenerative wound care, leveraging mechanically disaggregated cell–matrix constructs to modulate the wound microenvironment and promote tissue repair. This scoping review systematically analyzed clinical studies investigating ATMs and DMGs in acute and chronic wounds. Eight studies, comprising randomized controlled trials, observational studies, and case series, were identified, involving diverse wound types such as burns, ulcers, surgical dehiscence, and posttraumatic defects. All interventions utilized mechanical disaggregation (Rigenera^® system) to produce micrografts, which were applied via perilesional injection, scaffold-assisted delivery, or topical administration. Outcomes consistently demonstrated accelerated re-epithelialization, enhanced angiogenesis, improved scar remodeling, and low complication rates. In select studies, micrografts were combined with platelet-rich fibrin or stromal vascular fraction, suggesting potential synergistic effects. While one randomized trial showed superior healing outcomes with DMGs over collagen scaffolds, others yielded mixed results, likely reflecting heterogeneity in methodology and outcome measures. Overall, the available clinical evidence supports the safety, feasibility, and biological activity of micrograft-based therapies. However, larger, standardized, and mechanistically driven studies are required to validate their efficacy and define optimal protocols across wound etiologies. Full article

Background/Objectives: Atrophic nonunion presents a significant challenge in hand surgery, often resulting in chronic pain and functional disability. Traditional surgical treatments such as bone grafting and internal fixation may be insufficient. This study evaluates the feasibility, safety, and preliminary effectiveness of a regenerative-first surgical protocol that combines autologous bone micro-grafts with a fresh human amniotic membrane to create a biologically active regenerative chamber. Methods: A total of 8 patients (6 males, 2 females; age range: 22–56 years) with an atrophic nonunion of metacarpals and phalanges were treated using a regenerative-first surgical approach. Autologous bone was harvested from the iliac crest and mechanically disaggregated via Rigenera^® technology to obtain micro-grafts enriched with osteoprogenitor cells and extracellular matrix fragments. These were applied to the bone defect and wrapped in a fresh amniotic membrane, creating a biologically active chamber. Fixation was achieved using low-profile plates or screws, and all patients underwent early protected mobilization. Results: Radiographic consolidation was achieved in all patients within 2 months postoperatively. Functional outcomes at final follow-up demonstrated excellent or good results in Total Active Motion (TAM), with grip and pinch strength within normative ranges and minimal residual pain. Conclusions: This preliminary series suggests that combining autologous bone micro-grafts with an amniotic membrane in a regenerative surgical protocol is a promising strategy for managing atrophic nonunion in the hand. The approach was associated with rapid consolidation and excellent functional recovery. Further research with larger, controlled cohorts is warranted to validate efficacy and define standardized indications and techniques. Full article

Osteoarthritis (OA) is one of the most common joint diseases worldwide, predominantly present in elderly people. Being a major source of pain for patients, it is debilitating and leads inevitably to a reduction in quality of life. The management of OA needs a personalized and multidimensional approach, resulting in the emergence of new regenerative and non-invasive methods, such as the use of micrografts. In this pilot study, Rigenera^® Technology was employed to obtain micrografts of cartilage tissue to be injected into the knees of 10 patients with osteoarthritic pain. To assess the efficacy of the treatment concerning pain reduction at this site, patients were asked to complete KOOS and WOMAC questionnaire and a VAS test before and after the procedure. The results presented in this article show how Rigenera^® treatment can potentially improve OA symptoms, alleviating pain in patients. Full article

Autologous micrografting technology (AMT^®) involves the use of autologous micrografts to stimulate/enhance the repair of damaged tissue. This study assessed the efficacy and safety of the AMT^® procedure in patients with early stages of knee osteoarthritis. Briefly, the AMT^® procedure involved extraction of auricular cartilage, disaggregation using the Rigeneracons^® SRT in 4.0 mL of saline solution, and injection of the disaggregated micrografts into the external femorotibial compartment area of the affected knee. Ten patients (4 men, 6 women; age range: 37–84 years) were included in the study. In all patients, there was a steady improvement in knee instability, pain, swelling, mechanical locking, stair climbing, and squatting at 1- and 6-months post-procedure. Improvement in mobility was observed as early as 3 weeks post-procedure in 2 patients. Significant improvements were seen in mean scores of all five subscales of Knee Injury and Osteoarthritis Outcome Score (KOOS [KOOS symptoms, KOOS pain, KOOS ADL, KOOS sport and recreation, and KOOS quality-of-life]) between pre-procedure and 1- and 6-months post-procedure (all p ≤ 0.05). Autologous auricular cartilage micrografts obtained by AMT^® procedure (using Rigenera^® technology) is an effective and safe protocol in the treatment of early stage knee osteoarthritis. These encouraging findings need to be validated in a larger patient population and in a randomized clinical trial (RCT). Full article

Background: Tissue healing consists of four main phases: coagulation, inflammation, proliferation, and remodeling. In diabetic patients, this process is stagnant in the inflammatory stage, leading to chronic wounds. The aim of this study is to evaluate in an animal model the biological evidence related to the use of the Rigenera^® technology (Turin Italy), an innovative mechanical procedure to isolate autologous micrografts (AMG). Methods: Fifty male Wistar rats were divided into four groups: control (C), control treated with micrografts (CM), diabetic (DB), and diabetic treated with micrografts (DBM). The experimental setup involved: the quantification of the total collagen and elastic fibers; histopathological analysis; immunohistochemical analysis for collagen type I (COL1), collagen type III (COL3), vascular endothelial growth factor (VEGF-A), and interleukin 4 (IL4) and 10 (IL10); evaluation of the oxidative stress; measurement of gluthatione (GSH); and, finally, an enzyme-linked immunosorbent assay (ELISA) on tumor necrosis factor-α (TNF-α). Results: The AMG technology induces a faster healing process: VEGF-A, IL4, IL10, and GSH increased, while TNF-α and oxidative stress decreased. Conclusions: Animals treated with micrografts showed more favorable results for healing compared to those that did not receive treatment, demonstrating a positive participation of the micrografts in the treatment of difficult-to-heal wounds. Full article

The purpose of this study was to estimate the safety, feasibility, and efficacy of the intra-articular treatment of autologous microfragmented adipose tissue in dogs with spontaneous osteoarthritis (OA) in comparison with hyaluronic acid (HA), the standard intra-articular treatment. Specifically, it clinically evaluated pain and lameness, the radiographic progression of osteoarthritis, and synovial fluid inflammation. This was a prospective, single-center, parallel-group, randomized, controlled, in vivo clinical study. Participants (n = 40) received either a single intra-articular injection of microfragmented adipose tissue or a single intra-articular injection of HA (1:1). Clinical outcomes were determined using a specialistic clinician assessment obtained by the completion of a specific clinical form based on the Vesseur modified lameness classification system, a pain evaluation using the Visual Analogue Scale (VAS), the measurement of the range of motion (ROM) of the affected joint, limb circumference, and the owners’ score evaluation using the Canine Brief Pain Inventory (CBPI) for up to 6 months after the time of injection. Patients underwent a radiographic examination to establish the degree of OA in the affected joint, and synovial fluid samples were collected to assess the biochemical environment of the joint and evaluate and quantify the cellular population and the presence of three specific inflammation biomarkers for up to 60 days. The results of this study suggest that microfragmented autologous adipose tissue is safe and can effectively relieve pain and improve function in dogs with spontaneous articular OA. This one-step procedure is simple, timesaving, cost-effective, minimally invasive, and eliminates the need for complex and time-intensive cell culture processing. Furthermore, the clinical evidence and cytological results suggest better long-term pain control, resulting in an improvement in joint function, compared to HA treatment. The canine spontaneous OA model could play a key role in developing successful treatments for human medicine. Full article

Within the adult canine population, disabilities and symptoms including joint pain and functional impairment are commonly observed in articular cartilage lesions and present a challenging feat in the operating room. Clinical settings require less invasive and more minimally manipulated measures facilitated by innovative and advanced technology. Mesenchymal stem cells have recently been proposed and, furthermore, autologous adipose tissue administration via injection has emerged as a new albeit somewhat controversial therapeutic tool. The purpose of this study is to characterize canine autologous micro-fragmented adipose tissue (micrografts) by mechanical approach without substantial manipulations. Adipose tissue samples collected from six dogs were processed by a Rigenera device and by enzymatic digestion from two different body regions (lumbar and thigh region). Interestingly, the immunophenotypic analysis attested that cells from Rigenera^® were highly positive for the mesenchymal stem cells markers CD73 and CD90, less positive for hematopoietic CD45 and CD34, and negative for MHC class II antibodies (which play a role in immune responses). Finally, the Rigenera^® technology obtained micrografts with a 35% higher expression of the IL10 gene with relevant anti-inflammatory activities compared to the enzymatic digestion protocol. This evidence suggests a potential improved clinical outcome capable of modulating inflammation and immune responses. Full article

Rigenera^® is a novel class-1 medical device that produces micro-grafts enriched of progenitors cells without ex vivo manipulation of donor tissues. The manufacturer’s protocol has been supported for a wide variety of clinical uses in the field of regenerative medicine. This study aimed to evaluate its potential use for in vitro cell models. Human primary oral fibroblasts were cultured under standard conditions and processed through Rigenera^® over a time course of up to 5 min. Cell viability was assessed using a Trypan Blue exclusion test. It is possible to process fibroblasts through Rigenera^® although an initial reduction of cell viability was observed. Additionally, debris was evident in the cell suspension of the processed samples. Scanning electron microscopy (SEM) microanalysis of the debris and electron energy-loss spectroscopy confirmed the presence of metal wear possibly due to the processing conditions used in this study. Interestingly, pore sizes within Rigeneracons^® grids were found to range between 250–400 μm. This is the first report assessing the suitability of Rigenera^® and Rigeneracons^® for in vitro applications. Whilst Rigenera® workflow was found to be amenable to laboratory uses, our results strongly suggest that further research and development is necessary to support the utilization of this technology for enrichment of micro-graft derived cells and cell sorting in vitro. Full article

The aim of this study was to investigate the effect of the use of autologous micrografts obtained by the Rigenera® Micrografting Technology and xenograft on critical size defects created in the calvaria of rats. Forty-eight rats were randomly divided into four groups for each of the two evaluation times (15 and 30 days) (n = 6). After general anesthesia, a 5-mm diameter bone defect was created in the calvaria of each animal. Each defect was filled with the following materials: blood clot, autologous bone graft, xenograft, and xenograft associated with autologous micrografts. Histomorphometric and histological analysis showed that the group that have received the Rigenera® processed autologous micrografts combined with the xenograft and the group that received autologous bone graft resulted in greater bone formation in both time points when compared with the use of the xenograft alone and blood clot. Full article

Tissue engineering represents a novel approach that aims to exploit the use of biomaterials composed mainly of scaffolds, cells (or grafts), and growth factors capable of restoring a specific tissue. Biomaterials represent the future of dental and oral regeneration due to their biocompatibility and affinity with the receiving site. The aim of this review was to collect results and considerations about a new type of biomaterial based on the use of micrografts in combination with different scaffolds. Micrografts are tissue particles enriched with progenitor cells (PCs), which are defined as descendants of stem cells that can differentiate into specialized cells belonging to the same tissue. PCs in the oral cavity might be extracted from various tissues such as dental pulp, periosteum, or periodontal ligament. Moreover, these cells are easy to isolate through a mechanical process that allows for the filtration of cells with a diameter of 80 μm, in contrast with enzymatic procedures where reagents are used and various culture periods are needed. The aim of this review was to collect data regarding the use of micrografts, developed by a Rigenera^® chair-side machine, in oral regeneration evaluating the clinical, histological, and radiographical outcomes. There have been encouraging results for the application of micrografts in bone and periodontal regeneration, but further randomized clinical trials are needed to validate this promising outcome. Full article

Autologous fat grafting is a surgical technique in which adipose tissue is transferred from one area of the body to another, in order to reconstruct or regenerate damaged or injured tissues. Before reinjection, adipose tissue needs to be purified from blood and cellular debris to avoid inflammation and preserve the graft viability. To perform this purification, different enzymatic and mechanical methods can be used. In this study, we characterized in vitro the product of a closed automatic device based on mechanical disaggregation, named Rigenera^®, focusing on two sites of adipose tissue harvesting. At first, we optimized the Rigenera^® operating timing, demonstrating that 60 s of treatment allows a higher cellular yield, in terms of the cell number and growth rate. This result optimizes the mechanical disaggregation and it can increase the clinical efficiency of the final product. When comparing the extracted adipose samples from the thigh and abdomen, our results showed that the thigh provides a higher number of mesenchymal-like cells, with a faster replication rate and a higher ability to form colonies. We can conclude that by collecting adipose tissue from the thigh and treating it with the Rigenera^® device for 60 s, it is possible to obtain the most efficient product. Full article

Background: the RIGENERA trial assessed the efficacy of granulocyte-colony stimulating factor (G-CSF) in the improvement of clinical outcomes in patients with severe acute myocardial infarction. However, there is no evidence available regarding the long-term safety and efficacy of this treatment. Methods: in order to evaluate the long-term effects on the incidence of major adverse events, on the symptom burden, on the quality of life and the mean life expectancy and on the left ventricular (LV) function, we performed a clinical and echocardiographic evaluation together with an assessment using the Minnesota Living with Heart Failure Questionnaire (MLHFQ) and the Seattle Heart Failure Model (SHFM) at 10-years follow-up, in the patients cohorts enrolled in the RIGENERA trial. Results: thirty-two patients were eligible for the prospective clinical and echocardiography analyses. A significant reduction in adverse LV remodeling was observed in G-CSF group compared to controls, 9% vs. 48% (p = 0.030). The New York Heart Association (NYHA) functional class was lower in G-CSF group vs. controls (p = 0.040), with lower burden of symptoms and higher quality of life (p = 0.049). The mean life expectancy was significantly higher in G-CSF group compared to controls (15 ± 4 years vs. 12 ± 4 years, p = 0.046. No difference was found in the incidence of major adverse events. Conclusions: this longest available follow-up on G-CSF treatment in patients with severe acute myocardial infarction (AMI) showed that this treatment was safe and associated with a reduction of adverse LV remodeling and higher quality of life, in comparison with standard-of-care treatment. Full article