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Search Results (319)

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13 pages, 441 KB  
Communication
Platelet-Rich Plasma in Episiotomy Repair: A Critical Appraisal of a Sparse and Partly Non-Indexed Evidence Base and Rationale for a Randomized Controlled Trial
by Dragos Brezeanu, Ana-Maria Brezeanu, Traian-Virgiliu Surdu, Monica Surdu and Vlad Tica
Life 2026, 16(8), 1339; https://doi.org/10.3390/life16081339 - 15 Aug 2026
Viewed by 133
Abstract
Background: Episiotomy remains one of the most common obstetric procedures worldwide, and suboptimal healing of the perineal wound continues to cause pain, dehiscence, and long-term impairment of postpartum quality of life. Obstetric anal sphincter injury (OASI) carries the greatest risk of severe wound [...] Read more.
Background: Episiotomy remains one of the most common obstetric procedures worldwide, and suboptimal healing of the perineal wound continues to cause pain, dehiscence, and long-term impairment of postpartum quality of life. Obstetric anal sphincter injury (OASI) carries the greatest risk of severe wound morbidity among perineal trauma types and is managed with prophylactic antibiotics and adjunctive measures; episiotomy, by contrast, is repaired without a comparable prophylactic package and is far more frequent, so that even a modest per-case complication rate carries a substantial absolute burden. Platelet-rich plasma (PRP), an autologous concentrate rich in growth factors, has demonstrated favourable effects on wound healing and scar quality across several surgical contexts, including caesarean section, raising the question of whether it could similarly benefit episiotomy repair. Methods: We conducted a structured, date-stamped search of PubMed, Scopus and Google Scholar, together with two trial registries (ClinicalTrials.gov, WHO ICTRP), forward and backward citation tracking, and reference-list screening of relevant reviews (final search 24 July 2026), to identify clinical studies of PRP for obstetric episiotomy or intrapartum perineal wound healing. Results: Five primary clinical studies and one systematic review were identified. One single-centre randomized controlled trial of 200 primiparous women, published in a regionally indexed journal covered by neither PubMed nor Scopus, evaluated PRP specifically for episiotomy wound healing and reported significantly lower REEDA, Vancouver and pain scores in the PRP arm; it was not prospectively registered, reported neither a sample-size calculation nor blinded outcome assessment, lost 12% of participants to follow-up, and contains internal inconsistencies in the reported data. The remaining evidence comprises one randomized trial of PRP for postpartum levator ani muscle recovery (a distinct target, with a null result), one non-randomized comparative study in grade III–IV intrapartum perineal laceration repair, two case reports, and one broad systematic review of PRP in pelvic floor disorders in which episiotomy was not analyzed as a distinct entity. Conclusions: PRP for episiotomy healing is therefore not wholly untested, but the single existing randomized trial is small, methodologically limited, not independently replicated, and effectively invisible to conventional database searching. We describe this evidence base and introduce PRP-EpiHeal (ClinicalTrials.gov ID: NCT07669285), designed to provide the first prospectively registered, adequately powered and assessor-blinded randomized evidence on this question, with REEDA scale assessment at six weeks postpartum as the primary outcome. Full article
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26 pages, 1726 KB  
Review
Harnessing the Bio-Instructive Placental Extracellular Matrix: Structural Properties, Decellularization, and Applications in Regenerative Medicine
by Gianluca Fontana, Giulio Innamorati and Luca Giacomello
Int. J. Mol. Sci. 2026, 27(16), 7259; https://doi.org/10.3390/ijms27167259 - 14 Aug 2026
Viewed by 145
Abstract
The persistent shortage of donor organs and the inherent drawbacks of autologous grafts highlight the urgent need for advanced biomaterial scaffolds in regenerative medicine. Synthetic polymers and animal-derived matrices offer structural support, yet they frequently lack the biological complexity of native tissue or [...] Read more.
The persistent shortage of donor organs and the inherent drawbacks of autologous grafts highlight the urgent need for advanced biomaterial scaffolds in regenerative medicine. Synthetic polymers and animal-derived matrices offer structural support, yet they frequently lack the biological complexity of native tissue or carry translational liabilities—xenogeneic antigens, pathogen transmission risk, and batch variability. This review positions the human placenta as a compelling, ethically sourced, and abundant reservoir for fully human, xeno-free biomaterials. We examine the placenta’s distinct anatomical compartments and their rich complement of extracellular matrix (ECM) proteins, growth factors, and bioactive cytokines. These components confer potent pro-angiogenic, anti-inflammatory, antimicrobial, and immunomodulatory properties, enabling precise direction of cellular behavior and tissue regeneration. We systematically assess recent advances in decellularization and the processing strategies required to preserve these bioactivities while eliminating immunogenic material. By integrating current tissue engineering applications with the regulatory and ethical frameworks shaping clinical translation, we argue that placenta-derived matrices are uniquely positioned to transcend the limitations of conventional scaffolds and serve as a robust platform for future regenerative therapies. Full article
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49 pages, 1984 KB  
Review
Hydrogel Implementing Drug Delivery in Cranial Bone Tissue Engineering
by Martina Salvati, Alessia Vita, Alessandro Arcovito, Ornella Parolini, Federica Tiberio and Wanda Lattanzi
J. Funct. Biomater. 2026, 17(8), 401; https://doi.org/10.3390/jfb17080401 - 14 Aug 2026
Viewed by 252
Abstract
Cranial bone defects remain a significant clinical challenge due to their limited intrinsic regenerative capacity and the complexity of coordinating osteogenesis, angiogenesis, and immune responses within a confined and poorly vascularised environment. Conventional approaches, including autologous grafts and synthetic implants, provide structural support [...] Read more.
Cranial bone defects remain a significant clinical challenge due to their limited intrinsic regenerative capacity and the complexity of coordinating osteogenesis, angiogenesis, and immune responses within a confined and poorly vascularised environment. Conventional approaches, including autologous grafts and synthetic implants, provide structural support but fail to actively modulate the biological processes required for effective bone regeneration. In this context, hydrogel-based systems have emerged as versatile platforms for localized and controlled drug delivery in cranial bone tissue engineering (BTE). This review provides a comprehensive overview of hydrogel-based delivery strategies designed to regulate the spatiotemporal presentation of bioactive agents within cranial defects. The main classes of hydrogels, natural, synthetic, semi-synthetic, and hybrid systems, are discussed in relation to their physicochemical properties and suitability for drug delivery applications. Current delivery approaches are analysed, including cell-free systems (growth factors, peptides, bioactive ions, nucleic acids, and small molecules drugs), cell-based platforms, and multifunctional systems integrating secondary carriers such as nanoparticles (NPs), microparticles (MPs), and extracellular vesicles (EVs). Particular emphasis is placed on how hydrogel design parameters, including crosslinking density, degradation kinetics, and responsiveness to microenvironmental cues, govern therapeutic release and influence regenerative outcomes. Emerging strategies and key translational challenges are also highlighted. Full article
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27 pages, 4062 KB  
Review
Functional Biomaterials and 3D Bioprinting Approaches for Temporomandibular Joint Reconstruction: A Narrative Review
by Dobromira Shopova, Svetlin Aleksandrov and Mariya Ivanova Hristozova
J. Funct. Biomater. 2026, 17(8), 390; https://doi.org/10.3390/jfb17080390 - 8 Aug 2026
Viewed by 360
Abstract
The temporomandibular joint (TMJ) is a highly specialized synovial joint responsible for essential functions such as mastication, speech, and swallowing. Owing to its unique anatomical organization, complex biomechanics, and heterogeneous tissue composition, regeneration of the TMJ remains one of the greatest challenges in [...] Read more.
The temporomandibular joint (TMJ) is a highly specialized synovial joint responsible for essential functions such as mastication, speech, and swallowing. Owing to its unique anatomical organization, complex biomechanics, and heterogeneous tissue composition, regeneration of the TMJ remains one of the greatest challenges in craniofacial reconstructive surgery. Conventional treatment modalities, including autologous grafts, alloplastic prostheses, and total joint replacement, are associated with several limitations, including donor-site morbidity, prosthetic wear, limited biological integration, and the inability to restore native tissue architecture. Three-dimensional (3D) bioprinting has emerged as a promising regenerative strategy capable of fabricating patient-specific living constructs that closely mimic the structural and functional characteristics of the native joint. This review summarizes recent advances in TMJ bioprinting, with particular emphasis on the regeneration of the mandibular condylar fibrocartilage, subchondral bone, articular disc, and integrated osteochondral constructs. The literature search covered publications from January 2010 through March 2026, and it was conducted using major scientific databases, including PubMed/MEDLINE, Scopus, Web of Science, and Google Scholar. Current progress in cellular sources, including mesenchymal stem cells and induced pluripotent stem cells, biomaterials and bioinks, growth factor delivery, and multimaterial bioprinting technologies is discussed. Particular attention is given to the challenges associated with reproducing the complex osteochondral interface, achieving adequate vascularization, ensuring long-term mechanical stability, and directing tissue-specific cell differentiation. Emerging technologies, including four-dimensional (4D) bioprinting, decellularized extracellular matrix-based bioinks, artificial intelligence-assisted design, patient-specific computational modeling, and bioreactor-mediated tissue maturation, are highlighted as promising approaches to improve construct functionality and clinical translation. Although the clinical application of TMJ bioprinting remains in its early stages, rapid advances in regenerative medicine and biofabrication technologies indicate that personalized bioengineered joint reconstruction may become a viable therapeutic option for the treatment of severe temporomandibular joint disorders in the future. Full article
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19 pages, 1232 KB  
Review
Micro-Fragmented Adipose Tissue (MFAT) in Orthopedic Regenerative Medicine: A Narrative Review of the Biological Basis and Clinical Evidence
by Claire Yuan, Ashu K. Goyle, Maged Guirguis, Alan D. Kaye, Vahid Grami, Karan Dave, Ronald J. Kulich, Timothy Deer, David Rosenblum, Vwaire Orhurhu, Jamal J. Hasoon and Christopher L. Robinson
Int. J. Mol. Sci. 2026, 27(14), 6185; https://doi.org/10.3390/ijms27146185 - 10 Jul 2026
Viewed by 755
Abstract
Micro-fragmented adipose tissue (mFAT) is a promising autologous biologic in regenerative medicine because it provides a mechanically processed adipose-derived product that preserves native extracellular matrix architecture and a cellular milieu rich in mesenchymal stem cells, pericytes, growth factors, cytokines, and extracellular vesicles. Mechanistically, [...] Read more.
Micro-fragmented adipose tissue (mFAT) is a promising autologous biologic in regenerative medicine because it provides a mechanically processed adipose-derived product that preserves native extracellular matrix architecture and a cellular milieu rich in mesenchymal stem cells, pericytes, growth factors, cytokines, and extracellular vesicles. Mechanistically, mFAT is hypothesized to act largely through paracrine signaling that dampens inflammation, supports vascular stabilization, and promotes cartilage and soft-tissue repair; in vitro data suggest modulation of osteoarthritic synovial macrophage signaling, including reductions in chemokines such as CCL2 and CCL3. Preparation involves liposuction harvest followed by closed, sterile mechanical processing without enzymatic digestion or cell expansion, aligning with “minimal manipulation” concepts relevant to regulatory frameworks. Preclinical animal studies generally demonstrate favorable effects on synovial inflammation and cartilage matrix markers (e.g., glycosaminoglycan content) with limited adverse events. Clinically, the strongest body of evidence is in knee osteoarthritis, where multiple prospective and retrospective studies report improvements in pain and function from months to several years after single injections, though response rates vary and study designs are heterogeneous. Evolving data support potential benefit in hip osteoarthritis and select tendon conditions, but cohorts remain small. Overall, mFAT appears safe and potentially effective, yet larger, standardized, long-term randomized controlled trials and comparative studies versus platelet-rich plasma and bone marrow aspirate concentrates are needed to clarify indications, dosing, durability, and mechanisms in vivo. Full article
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18 pages, 4506 KB  
Article
Regenerative Potential of Autologously Processed White Adipose Tissue for Peripheral Nerve Regeneration: Evaluation of Growth Factor Profiles and Electrical Stimulation
by Tobias Egger, Andreas Eigenberger, Oliver Felthaus, Marc Ruewe, Luis Sturz, Christian Festbaum, Dmytro Oliinyk, Andreas Siegmund, Tom Schimanski, Katharina Rosengarth, Daniel Deuter, Philipp Kreiner, Lukas Prantl and Silvan M. Eisenmann
Cells 2026, 15(14), 1250; https://doi.org/10.3390/cells15141250 - 10 Jul 2026
Viewed by 377
Abstract
Peripheral nerve injuries (PNI) present a major clinical and socioeconomic challenge due to limited regenerative capacity. Adipose-derived stem cells (ADSCs) within the stromal vascular fraction (SVF) of white adipose tissue offer a promising autologous source for regenerative support. This study evaluated the impact [...] Read more.
Peripheral nerve injuries (PNI) present a major clinical and socioeconomic challenge due to limited regenerative capacity. Adipose-derived stem cells (ADSCs) within the stromal vascular fraction (SVF) of white adipose tissue offer a promising autologous source for regenerative support. This study evaluated the impact of mechanical processing CELT (Cell-Enriched Lipotransfer) and CELTPLUS and electrical stimulation on the regenerative secretome of human lipoaspirates. qPCR analysis revealed that CELTPLUS processing, which incorporates mechanical intersyringe shifting, significantly doubled the gene expression of nerve growth factor (NGF) (p = 0.015), vascular endothelial growth factor (VEGF) (p = 0.02), and brain-derived neurotrophic factor (BDNF) (p = 0.04) compared to CELT-processed lipoaspirate. Protein analysis via ELISA confirmed a time-dependent secretion of NGF and VEGF over 96 h. Furthermore, 24 h electrical stimulation (2 V) significantly enhanced NGF protein release (p < 0.001). These findings demonstrate that standardized mechanical processing effectively enriches regenerative cell populations and amplifies their neurogenic and angiogenic potential. The additional modulation of growth factor secretion via electrical stimulation highlights the potential of processed adipose tissue as a functional, autologous transplant for enhanced nerve reconstruction. Full article
(This article belongs to the Collection Research on Adipose Stem Cells)
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16 pages, 2256 KB  
Review
Mapping the Prosthetic–Host Interactome: From Systemic Inflammation to Biological Integration in Mesh-Enhanced Therapies METs—A Scoping Review
by Florentina Cristina Finascu, Valentin Constantin Oprea, Mihai Toma, Carmen Elena Bucuri, Calin Molnar, Bogdan Andrei Finascu, Bianca Liana Grigorescu and Bogdan Andrei Suciu
Int. J. Mol. Sci. 2026, 27(14), 6153; https://doi.org/10.3390/ijms27146153 - 9 Jul 2026
Viewed by 436
Abstract
Despite reducing hernia recurrence, synthetic meshes often trigger persistent foreign body responses (FBRs). Mesh-enriched therapies (METs), incorporating autologous cellular components (MSCs, PRP, SVF), can regeneratively reprogram the host-prosthetic interactome. Following PRISMA-ScR guidelines, this scoping review involved a systematic search of PubMed, Embase, and [...] Read more.
Despite reducing hernia recurrence, synthetic meshes often trigger persistent foreign body responses (FBRs). Mesh-enriched therapies (METs), incorporating autologous cellular components (MSCs, PRP, SVF), can regeneratively reprogram the host-prosthetic interactome. Following PRISMA-ScR guidelines, this scoping review involved a systematic search of PubMed, Embase, and Scopus (2000–2025). We utilized the PCC (Population, Concept, Context) framework to map evidence across systemic inflammation, local FBR, and bio-augmentation strategies. A total of sixty-five studies were synthesized and categorized into three primary thematic pillars. Regarding the Systemic Response (n = 25), the data established a predictable “foreign body signature” characterized by prominent C-reactive protein (CRP) and interleukin-6 (IL-6) spikes within the first 48 h post-implantation. For the Local Foreign Body Reaction (FBR, n = 19), human explant data extending up to 180 months revealed a perpetual, immune-mediated state driven by matrix metalloproteinase-2 (MMP-2) matrix remodeling and the development of “bridging fibrosis.” Finally, concerning Mesh-Enriched Therapy (MET) Integration (n = 21), biological enrichment successfully shifted the M1/M2 macrophage ratio toward a pro-regenerative, CD163+/CD206+ phenotype. While MET consistently enhanced vascular endothelial growth factor (VEGF)-driven angiogenesis and optimized the Collagen I/III ratio, a notable 22.2% discrepancy rate across the literature underscores the critical need for precise transforming growth factor-beta 1 (TGF-β1) dosing and release kinetics to prevent hyper-fibrosis. MET shifts hernia repair from passive mechanical reinforcement to active “biocamouflage” and integration. By modulating the Th1/Th2 rheostat, enriched therapies mitigate chronic inflammation and long-term complications. Standardized clinical trials are essential to optimize the therapeutic window for hybrid integration. Full article
(This article belongs to the Section Molecular Pathology, Diagnostics, and Therapeutics)
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8 pages, 218 KB  
Case Report
Occupational Meralgia Paresthetica in a Professional Diving Instructor Successfully Treated with Platelet-Rich Plasma: A Case Report
by Ivan Medina-Porqueres, Pablo Martin-Garcia, Sofia Sanz-De Diego, Marcelo Reyes-Eldblom, Daniel Rosado-Velazquez and Abel Gomez-Caceres
Biologics 2026, 6(2), 19; https://doi.org/10.3390/biologics6020019 - 22 Jun 2026
Viewed by 594
Abstract
Background: Meralgia paresthetica (MP) of the lateral femoral cutaneous is a rare, nerve-entrapment condition, often related to an inflammatory and fibrotic pathological component. Although most cases resolve with conservative management, refractory presentations may require interventional or surgical treatment. Platelet-rich plasma (PRP) has [...] Read more.
Background: Meralgia paresthetica (MP) of the lateral femoral cutaneous is a rare, nerve-entrapment condition, often related to an inflammatory and fibrotic pathological component. Although most cases resolve with conservative management, refractory presentations may require interventional or surgical treatment. Platelet-rich plasma (PRP) has demonstrated emerging potential in peripheral neuropathies through anti-inflammatory, neurotrophic, and antifibrotic mechanisms. Case Presentation: We report the case of a 64-year-old professional scuba diving instructor with occupational MP related to repetitive compression from a tight lead weight belt. Symptoms persisted for six months despite conservative therapies. Clinical examination supported lateral femoral cutaneous nerve (LFCN) entrapment. The patient underwent three serial perineural PRP injections prepared from autologous blood and administered along the inguinal course of the nerve. Progressive symptom reduction was observed after each session, reaching approximately 90% improvement at two months. At six months, the patient was pain-free and had returned to full professional activity without limitations. Discussion: Occupational microcompression may induce intraneural edema, ischemia, and perineural fibrosis, creating a biological substrate amenable to regenerative intervention. PRP delivers concentrated growth factors capable of promoting axonal regeneration, angiogenesis, and modulation of the neuroinflammatory microenvironment. Preclinical and clinical evidence in other compressive neuropathies supports this translational rationale. Conclusions: Perineural PRP infiltration may represent a safe and promising regenerative strategy for refractory occupational MP. Controlled clinical studies are needed to define optimal protocols, patient selection criteria, and long-term efficacy in peripheral compressive neuropathies. Full article
(This article belongs to the Section Blood Products)
23 pages, 3974 KB  
Article
Clinical Application of Heparin-Conjugated Fibrin Hydrogel in the Treatment of Osteochondral Defects of the Talus: Preliminary Results
by Dina Saginova, Meruyert Makhmetova, Yerik Raimagambetov, Bagdat Balbossynov, Vyacheslav Ogay and Ulunay Kanatli
Biomedicines 2026, 14(6), 1398; https://doi.org/10.3390/biomedicines14061398 - 21 Jun 2026
Viewed by 438
Abstract
Background: Osteochondral lesions of the talus (OLT) remain a challenging condition due to the limited regenerative potential of articular cartilage. Conventional bone marrow stimulation (BMS) techniques often result in fibrocartilage formation with inferior biomechanical properties. This study aimed to evaluate the safety [...] Read more.
Background: Osteochondral lesions of the talus (OLT) remain a challenging condition due to the limited regenerative potential of articular cartilage. Conventional bone marrow stimulation (BMS) techniques often result in fibrocartilage formation with inferior biomechanical properties. This study aimed to evaluate the safety and preliminary clinical efficacy of an arthroscopically assisted, single-stage injection of a heparin-conjugated fibrin hydrogel (HCFH) for OLT treatment. Methods: Twelve patients with symptomatic OLT underwent arthroscopic debridement, microfracturing, and HCFH injection containing autologous mesenchymal stromal cells (MSCs) and growth factors. Safety was assessed through systematic monitoring of adverse events (graded according to Common Terminology Criteria for Adverse Events criteria), wound healing, and serial laboratory inflammatory markers (leukocytes, erythrocyte sedimentation rate, C-reactive protein) during early and late follow-up. Clinical outcomes were evaluated using the Visual Analog Scale (VAS) and American Orthopedic Foot and Ankle Society score (AOFAS) preoperatively and at 6 and 12 months. Morphological assessment was performed using magnetic resonance imaging (MRI) with the modified Magnetic Resonance Observation of Cartilage Repair Tissue (MOCART) scoring system, evaluated independently by two blinded musculoskeletal radiologists. Results: No serious adverse events (Grade III–IV) were observed during the 12-month follow-up. All adverse events were mild (Grade I) and self-limited. A transient postoperative elevation in inflammatory markers was observed, returning to clinically acceptable levels by day 14. Significant improvements were noted in pain (VAS decreased from 6.0 to 2.0) and ankle function (AOFAS increased from 70.0 to 90.6) (p < 0.001). MRI demonstrated progressive morphological improvement, with the MOCART score increasing from 34.16 ± 17.1 at 6 months to 75 ± 5.43 at 12 months (p < 0.001). This increase corresponded with imaging features consistent with tissue maturation over time. The favorable MOCART outcomes observed in this study may be explained by the regenerative properties of heparin-conjugated fibrin hydrogels; however, larger randomized controlled trials with longer follow-up are needed to confirm the durability of the regenerated tissue. Interobserver agreement was substantial to almost perfect for MOCART scoring (κ = 0.68–0.84), with perfect agreement observed for surface assessment, bony defect/overgrowth, and cysts. Conclusions: Within the limitations of this study, single-stage HCFH injection demonstrated an acceptable safety profile and favorable preliminary clinical and radiological outcomes at 12 months. These findings suggest potential regenerative capability; however, controlled studies with larger cohorts and longer follow-up are required to determine comparative efficacy and long-term durability. Full article
(This article belongs to the Section Biomedical Engineering and Materials)
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22 pages, 668 KB  
Systematic Review
Autologous Nanofat Indications in Wound Healing: A Systematic Review
by Stefanie Bonini, Patricia Fuentes and Richard Brannon Claytor
Biomedicines 2026, 14(6), 1215; https://doi.org/10.3390/biomedicines14061215 - 28 May 2026
Viewed by 519
Abstract
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 [...] Read more.
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
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25 pages, 1128 KB  
Review
Platelet-Rich Plasma Versus Injectable Platelet-Rich Fibrin in the Management of Temporomandibular Joint Osteoarthritis: A Narrative Review
by Tânia Martins, Bruno Daniel Carneiro, Carlos Silva Faria and Daniel Humberto Pozza
Biologics 2026, 6(2), 16; https://doi.org/10.3390/biologics6020016 - 21 May 2026
Viewed by 1299
Abstract
Temporomandibular joint osteoarthritis (TMJ-OA) is a multifactorial degenerative disorder characterized by progressive cartilage degradation, subchondral bone remodeling, and chronic inflammation, leading to pain and functional impairment in affected individuals. Despite its clinical impact, effective disease-modifying treatments remain limited, highlighting the need for innovative [...] Read more.
Temporomandibular joint osteoarthritis (TMJ-OA) is a multifactorial degenerative disorder characterized by progressive cartilage degradation, subchondral bone remodeling, and chronic inflammation, leading to pain and functional impairment in affected individuals. Despite its clinical impact, effective disease-modifying treatments remain limited, highlighting the need for innovative therapeutic approaches for treating this condition in the future. This manuscript examines the biological rationale, clinical applications, and therapeutic potential of platelet-rich plasma (PRP) and injectable platelet-rich fibrin (i-PRF) in the management of TMJ-OA. As autologous platelet-derived biomaterials, PRP and i-PRF contain high concentrations of growth factors and bioactive molecules that can modulate inflammatory responses and support tissue repair. PRP is associated with a relatively rapid release of these mediators, whereas i-PRF forms a fibrin matrix that may enable a more sustained release profile. Current clinical evidence suggests that both therapies show potential to contribute to pain reduction and may facilitate improvements in mandibular function. However, substantial heterogeneity in preparation protocols, study designs, and outcome measures limits the comparability and generalizability of these findings to the general population. Overall, PRP and i-PRF represent promising, minimally invasive regenerative strategies for managing TMJ-OA. Full article
(This article belongs to the Section Blood Products)
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28 pages, 5518 KB  
Article
Low-Frequency Electrical Stimulation Optimizes Neurotrophic and Neuroimmune Signaling in Bisvinyl Sulfonemethyl-Based Nerve Guidance Conduits
by Ching-Feng Su, Chung-Chia Chen, Wei-Cheng Hsu, Ming-Hsuan Lu, Joanna Pi-Jung Lee, Yung-Hsiang Chen and Yueh-Sheng Chen
Int. J. Mol. Sci. 2026, 27(9), 3820; https://doi.org/10.3390/ijms27093820 - 25 Apr 2026
Viewed by 824
Abstract
Peripheral nerve injuries involving critical-sized gaps remain a major clinical challenge. Although autologous nerve grafting is considered the gold standard for peripheral nerve repair, its clinical application is limited by the availability of donor nerve tissue and the risk of donor-site morbidity, including [...] Read more.
Peripheral nerve injuries involving critical-sized gaps remain a major clinical challenge. Although autologous nerve grafting is considered the gold standard for peripheral nerve repair, its clinical application is limited by the availability of donor nerve tissue and the risk of donor-site morbidity, including sensory deficits and functional impairment. Therefore, nerve guidance conduits (NGCs) have emerged as a promising alternative when combined with bioactive modulation strategies. In this study, we evaluated bisvinyl sulfonemethyl (BVSM)-crosslinked gelatin conduits integrated with electrical stimulation (ES) at different frequencies (0, 2, 20, and 200 Hz) in a rat sciatic nerve defect model over a 4-week recovery period (n = 10 per group). Structural regeneration was assessed by morphometric analysis, electrophysiology, macrophage infiltration, CGRP immunoreactivity, retrograde Fluorogold tracing, quantitative PCR of growth factors and inflammatory cytokines, and behavioral testing. Among all stimulation paradigms, low-frequency ES at 2 Hz produced the most pronounced regenerative effects. The 2 Hz group demonstrated significantly greater axon number, axonal density, and regenerated nerve area compared with control and high-frequency groups (p < 0.05). Electrophysiological assessments revealed improved nerve conduction velocity, higher MAP amplitudes, and shorter latencies. Enhanced macrophage recruitment and elevated CGRP expression were observed, suggesting coordinated neuroimmune and neurochemical activation. Gene expression analysis indicated upregulation of neurotrophic factors and balanced inflammatory cytokine responses under low-frequency stimulation. In contrast, high-frequency stimulation (200 Hz) failed to enhance overall regeneration and showed reduced axonal metrics, suggesting possible overstimulation-associated suppression. Collectively, these findings demonstrate that BVSM-crosslinked conduits provide a stable and biocompatible regenerative scaffold, and that appropriately tuned low-frequency electrical stimulation (2 Hz) optimally enhances structural, molecular, and functional recovery. The integration of material engineering with bioelectrical modulation represents a promising strategy for next-generation bioelectronic interfaces in peripheral nerve repair. Full article
(This article belongs to the Special Issue Advancements in Regenerative Medicine Research)
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28 pages, 1280 KB  
Review
Recent Advances in Thalassemia Management: From Curative Therapies to Artificial Intelligence
by Mohamed Medhat Abdelwahab Gamaleldin, Shaimaa Mahmoud Nashat Sayed Abdelhalim and Ivo Abraham
Thalass. Rep. 2026, 16(2), 7; https://doi.org/10.3390/thalassrep16020007 - 22 Apr 2026
Viewed by 2277
Abstract
Thalassemia is an inherited hemoglobin disorder characterized by chronic hemolytic anemia and substantial long-term healthcare needs. In β-thalassemia major, patients typically require regular red blood cell transfusions with iron chelation to prevent transfusional iron overload. Although supportive care has markedly improved survival, it [...] Read more.
Thalassemia is an inherited hemoglobin disorder characterized by chronic hemolytic anemia and substantial long-term healthcare needs. In β-thalassemia major, patients typically require regular red blood cell transfusions with iron chelation to prevent transfusional iron overload. Although supportive care has markedly improved survival, it is associated with a high treatment burden and does not provide a cure. In recent years, curative and disease-modifying therapies have expanded the treatment landscape. Allogeneic hematopoietic stem cell transplantation (HSCT) offers a potentially curative option for selected patients, while autologous gene therapy and gene-editing approaches have shown the capacity to achieve transfusion independence in clinical studies. In parallel, pharmacologic advances—including luspatercept, a transforming growth factor-beta (TGF-β) ligand trap—have been shown to enhance erythropoiesis and reduce transfusion requirements, and emerging agents such as fetal hemoglobin inducers (e.g., thalidomide) and the oral pyruvate kinase activator mitapivat have demonstrated clinically meaningful hemoglobin improvements in selected populations. Adjunctive strategies, including antioxidants, are under investigation to mitigate oxidative stress, and applications of artificial intelligence are increasingly used to support screening, diagnosis, and longitudinal monitoring of iron overload. This review synthesizes recent advances in curative therapies, novel pharmacologic agents, supportive strategies, and AI-enabled tools and highlights priorities for future clinical development and implementation. Full article
(This article belongs to the Collection Feature Papers in Thalassemia Reports)
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13 pages, 1503 KB  
Article
A Single-Institution Cohort Study of Autologous Platelet-Rich Plasma Gel for Hard-to-Heal Chronic Wounds: Potential Role in Microvascular Regeneration
by Miki Fujii, Kazuki Shimada, Takako Komiya and Hajime Matsumura
J. Clin. Med. 2026, 15(8), 3120; https://doi.org/10.3390/jcm15083120 - 19 Apr 2026
Viewed by 822
Abstract
Background/Objectives: Chronic wounds that fail to respond to standard wound care (SWC) remain a major clinical challenge. Platelet-rich plasma (PRP) is an advanced regenerative therapy that delivers platelet-derived growth factors involved in angiogenesis and tissue repair. However, clinical data in Asian populations and [...] Read more.
Background/Objectives: Chronic wounds that fail to respond to standard wound care (SWC) remain a major clinical challenge. Platelet-rich plasma (PRP) is an advanced regenerative therapy that delivers platelet-derived growth factors involved in angiogenesis and tissue repair. However, clinical data in Asian populations and evidence regarding ulcers associated with vasculitis or microangiopathic ischemia remain limited. This study evaluated the efficacy, safety, and treatment frequency of autologous PRP gel prepared using the newly approved AutoloGel System® in Japan. Methods: This single-center retrospective study included 20 patients with chronic ulcers unresponsive to ≥28 days of conventional therapy by a wound specialist. PRP gel was applied weekly for up to eight sessions under current insurance coverage. Primary outcomes were wound healing rate at 12 weeks after PRP initiation and healing duration. Healing time during specialist-directed conventional therapy was compared with that following PRP using the Wilcoxon signed-rank test. Results: Twenty patients (mean age 60 ± 15 years) with diverse refractory ulcers—including diabetic foot ulcers, chronic limb-threatening ischemia, vasculitic ulcers, venous leg ulcers, pressure ulcers, and surgical site infections—were analyzed. All wounds achieved complete epithelialization within 12 weeks. Healing time decreased significantly from 87.2 ± 77.1 days during conventional therapy to 47.9 ± 28.5 days after PRP initiation (median 60 vs. 44 days, p = 0.0107). No treatment-related adverse events were observed. Conclusions: Weekly autologous PRP gel therapy prepared using the AutoloGel System® was associated with improved healing outcomes in refractory chronic wounds. Favorable outcomes were observed in traditionally difficult-to-treat conditions, including vasculitis-associated and microangiopathic ischemic ulcers. These findings suggest the potential role of PRP in promoting angiogenesis and improving microcirculatory perfusion in wounds associated with microvascular dysfunction. Full article
(This article belongs to the Special Issue New Advances in Wound Healing and Skin Wound Treatment)
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Article
Alb-PRF Hybrid Membranes Functionalized with Carbonated Hydroxyapatite and Doxycycline for Bone Regeneration and Antimicrobial Control: An In Vitro Study
by Neilane Rodrigues Santiago Rocha, Emanuelle Stellet Lourenço, Victor Hugo de Souza Lima, Carlos Alberto Soriano, Alexandre Malta Rossi, Carolina N. Spiegel, Monica Diuana Calasans-Maia, Carlos Fernando Mourão and Gutemberg Gomes Alves
Int. J. Mol. Sci. 2026, 27(8), 3639; https://doi.org/10.3390/ijms27083639 - 19 Apr 2026
Cited by 1 | Viewed by 551
Abstract
Bone tissue engineering requires biomaterials capable of simultaneously supporting regeneration and preventing infection. Platelet-rich fibrin (PRF) has been widely used due to its autologous origin and growth factor release, but its rapid resorption limits its clinical applications. Albumin-PRF (Alb-PRF) membranes were developed to [...] Read more.
Bone tissue engineering requires biomaterials capable of simultaneously supporting regeneration and preventing infection. Platelet-rich fibrin (PRF) has been widely used due to its autologous origin and growth factor release, but its rapid resorption limits its clinical applications. Albumin-PRF (Alb-PRF) membranes were developed to improve stability, and their combination with carbonated nanostructured hydroxyapatite (nCHA) may further reinforce osteoconductive properties. In this proof-of-concept study, we fabricated Alb-PRF, Alb-nCHA-PRF, and Alb-nCHA-PRF + doxycycline (DOX) membranes and characterized their physicochemical, antimicrobial, and biological performance in vitro. Membrane stability was monitored for up to 14 days; DOX incorporation and release were evaluated by autofluorescence and spectrophotometry; antimicrobial activity was assessed against E. faecalis and S. aureus; and MG-63 osteoblast-like cells were used to test cytocompatibility, proliferation, mineralization, and alkaline phosphatase (ALP) activity. The release of 27 cytokines and growth factors was quantified by multiplex immunoassay. Alb-PRF exhibited morphological integrity and an enhanced trophic secretome, and supported proliferation and late mineralization. nCHA incorporation reduced cell proliferation and secretome output, while DOX conferred sustained antibacterial activity and enhanced early ALP expression even with attenuated cytokine release, positively impacting mineralization, when compared to nCHA alone. These preliminary results provide preliminary feasibility evidence that Alb-PRF can be engineered as a multifunctional scaffold combining antimicrobial and regenerative functions, though some trade-offs indicate the need for dose optimization and validation with in vivo models. Full article
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