Search Results (246)

Bone defects in the maxillofacial region severely impair patient function and esthetics. Free autologous bone grafting remains the gold-standard treatment; however, surgical intervention at donor sites limits clinical applicability. Treatment using artificial materials also presents challenges, including insufficient bone regeneration and poor biocompatibility. Bio three-dimensional (3D) printing, which enables the fabrication of scaffold-free 3D constructs from cellular spheroids has emerged as a promising regenerative approach. This study investigated the osteogenic potential of scaffold-free constructs composed of human dental pulp stem cell (DPSC) spheroids in a rat mandibular defect model. DPSCs isolated from extracted human teeth were used to generate spheroids, which were assembled into 3D constructs using a Bio 3D printer. The spheroids exhibited higher mRNA expression of stem cells and early osteogenic markers than monolayer cultures. The constructs were transplanted into mandibular defects of immunodeficient rats, and bone regeneration was assessed eight weeks post-transplantation. Radiographic and micro-Computed Tomography analyses revealed significantly greater bone volume and mineral density in the 3D construct group. Histological and immunohistochemical examinations confirmed newly formed bone containing osteogenic cells derived from the transplanted DPSCs. These findings indicate that Bio 3D-printed, scaffold-free DPSC constructs promote mandibular bone regeneration and may provide a novel strategy for maxillofacial reconstruction. Full article

Craniofacial bone defects of critical size, caused by trauma, tumors, infections, or congenital maldevelopment, represent a major challenge in plastic and reconstructive surgery. Autologous bone grafting is considered the gold standard, but limitations such as donor site morbidity and limited availability have prompted the development of artificial bone tissue engineering scaffolds. In recent years, bioactive scaffolds have been increasingly utilized in favor of inert biomaterials due to their immunomodulation and osteoinduction capabilities. This review methodically summarizes loading strategies for the functionalization of scaffolds with bioactive components, including cell regulatory factors, drugs, ions, stem cells, exosomes, and components derived from human tissues or cells to promote bone regeneration. The following mechanisms are involved: (1) the polarization of macrophages (M1-M2 transition), (2) the dynamic regulation of bone metabolism, and (3) the coupling of osteogenesis and angiogenesis. This review focuses on innovative delivery systems, such as 3D-printed scaffolds, nanocomposites and so on, that enable spatiotemporal control of bioactive cargo release. These address key challenges, such as infection resistance, vascularization, and mechanical stability in the process of bone regeneration. In addition, the article discusses emerging technologies, including stem cells and exosome-based acellular therapies, which demonstrate potential for personalized bone regeneration. This review integrates immunology, materials science, and clinical needs, providing a roadmap for the design of next-generation bone tissue engineering scaffolds to overcome critical-sized bone defects. Full article

Background: Articular cartilage has limited self-repair capacity. While thermoresponsive poly N-isopropyl acrylamide (pNIPAAm)-based Cell Sheet Engineering (CSE) is a promising scaffold-free strategy, its inherent material properties pose limitations. This study developed and validated a novel, non-thermoresponsive CSE platform for functional cartilage regeneration. Methods: A culture platform was fabricated by grafting the biocompatible polymer poly gamma-glutamic acid (γ-PGA) and a disulfide-containing amino acid onto porous PET membranes. This design enables intact cell sheet detachment with its native extracellular matrix (ECM) via specific cleavage of the disulfide bonds by a mild reducing agent. Results: The hydrated substrate exhibited a biomimetic stiffness (~16.2 MPa) that closely mimics native cartilage. The platform showed superior biocompatibility and supported the cultivation of multi-layered rabbit chondrocyte sheets rich in Collagen II and Glycosaminoglycans. Critically, in a rabbit full-thickness defect model, transplanted autologous cell sheets successfully regenerated integrated, hyaline-like cartilage at 12 weeks, as confirmed by MRI, CT, and histological analyses. Conclusions: This novel CSE platform, featuring highly biomimetic stiffness and a gentle, chemically specific detachment mechanism, represents a highly promising clinical strategy for repairing articular cartilage defects. Full article

Purpose: The increasing demand for alternatives to autologous and resorbable bone grafts in the treatment of bone defects is driving research efforts. This study aims to evaluate the effects of different surface treatments on zinc-1%-magnesium (Zn-1Mg) alloy scaffolds on chondrocytes and osteoblasts, focusing on cytotoxicity, biocompatibility, and cell proliferation. Methods: Zn-1Mg alloy disks were manufactured additively by the powder bed fusion of metals using a laser beam (PBF-LB/M) and underwent different distinct surface treatments, including as-built treatment, sandblasting, Zn-1Mg-blasting, and electropolishing, respectively. Chondrocytes and osteoblasts were cultured separately on these additively manufactured Zn-1Mg alloy disks for 3, 7, and 14 days to assess biocompatibility and cellular growth. Cell viability, cytotoxicity, and proliferation were analyzed using DAPI staining, live/dead staining, fluorescence microscopy, and flow cytometry. Additionally, cellular morphology was investigated using Phalloidin/DAPI staining and scanning electron microscopy (SEM). Zn-1Mg scaffolds were also manufactured and subjected to the same surface treatments. All aforementioned experiments were repeated using Zn-1Mg scaffolds with co-cultured osteoblasts and chondrocytes. Results: All samples, irrespective of the surface treatment, showed similar effects compared to the reference surfaces in terms of cell viability, cytotoxicity, and proliferation for both chondrocytes and osteoblasts. SEM analysis revealed comparable cellular morphology across all scaffolds, with cells observed attaching and growing on all scaffold surfaces. This indicates that all scaffolds independent of different surface treatments exhibit good biocompatibility. Conclusions: The findings indicate that Zn-1Mg alloy samples with different surface treatments exhibit no significant differences in cytocompatibility with chondrocytes and osteoblasts. Zn-1Mg alloy scaffolds, composed of 99% zinc and 1% magnesium, demonstrate biocompatibility, with cells attaching and growing on all scaffold surfaces. These results suggest that Zn-1Mg alloy scaffolds manufactured additively by PBF-LB/M hold promise for use in resorbable bone graft applications. Full article

Osteochondral lesions of the talus (OLTs) present a significant clinical challenge, often leading to pain, dysfunction, and joint degeneration. Traditional treatments, including microfracture and grafting, have limitations in their ability to fully restore osteochondral integrity. Recent advances in tissue engineering have introduced heparin-conjugated fibrin hydrogel (HCFH) as a promising scaffold for regenerative therapy. By supporting mesenchymal stem cell (MSC) proliferation and controlled growth factor release, HCFH enhances cartilage and bone repair. A 21-year-old female presented with chronic right ankle pain and instability following a sports injury, with MRI revealing an osteochondral lesion in the lateral dome of the talus and an anterior talofibular ligament injury. Treatment included autologous MSC isolation, HCFH synthesis, arthroscopic debridement, microfracture, and implantation of MSC-loaded HCFH, while postoperative rehabilitation involved four weeks of restricted weight-bearing- and physiotherapy. At 12 months, her visual analog scale (VAS) score decreased from 60 to 40, indicating clinical improvement, and her American Orthopaedic Foot and Ankle Society (AOFAS) score increased from 69 to 77. Serial MRI scans showed progressive cartilage regeneration with near-complete defect filling. This case highlights the potential of MSC-loaded HCFH in treating OLTs. The observed improvements in pain relief, function, and cartilage regeneration suggest that this technique may overcome the limitations of conventional treatments. Further studies with larger cohorts and long-term follow-up are necessary to confirm its clinical efficacy. Full article

Platelet-rich plasma (PRP) is an autologous blood-derived concentrate increasingly utilized in regenerative medicine for its ability to accelerate healing and tissue repair. PRP is broadly classified by leukocyte content, fibrin architecture, and platelet concentration, with classification systems developed to standardize characterization. Preparation methods, including single- or double-spin centrifugation and buffy coat techniques, influence the final composition of PRP, determining the relative proportions of platelets, leukocytes, plasma proteins, and extracellular vesicles. These components act synergistically, with platelets releasing growth factors (e.g., VEGF, PDGF, TGF-β) that stimulate angiogenesis and matrix synthesis, leukocytes providing immunomodulation, plasma proteins facilitating scaffolding, and exosomes regulating intercellular signaling. Mechanistically, PRP enhances tissue repair through four key pathways: platelet adhesion molecules promote hemostasis and cell recruitment; immunomodulation reduces pro-inflammatory cytokines and favors M2 macrophage polarization; angiogenesis supports vascular remodeling and nutrient delivery; and serotonin-mediated pathways contribute to analgesia. These processes establish a regenerative microenvironment that supports both structural repair and functional recovery. Clinically, PRP has been applied across multiple specialties. In orthopedics, it promotes tendon, cartilage, and bone healing in conditions such as tendinopathy and osteoarthritis. In dermatology, PRP enhances skin rejuvenation, scar remodeling, and hair restoration. Gynecology has adopted PRP for ovarian rejuvenation, endometrial repair, and vulvovaginal atrophy. In dentistry and oral surgery, PRP accelerates wound closure and osseointegration, while chronic wound care benefits from its angiogenic and anti-inflammatory effects. PRP has also favored gingival recession coverage, regeneration of intrabony periodontal defects, and sinus grafting. Although preparation heterogeneity remains a challenge, PRP offers a versatile, biologically active therapy with expanding clinical utility. Full article

Background: This study evaluates the impact of fibrinogen enrichment on the structural, mechanical, and bioactive properties of fibrin scaffold derived from balanced protein-concentrate plasma (BPCP), an autologous platelet-rich plasma (PRP) formulation with elevated extraplatelet content. Methods: A novel high-fibrinogen BPCP (HF-BPCP) scaffold was produced by combining BPCP platelet lysate with a concentrated fibrinogen solution at a 1:1 ratio, yielding nearly four-fold physiological fibrinogen levels. Comparative analyses between HF-BPCP and standard BPCP included platelet and fibrinogen quantification, scanning electron microscopy (SEM), rheology, indentation, adhesion testing, coagulation kinetics, retraction assays, biodegradation profiling, and growth factor (GF) release kinetics. Results: HF-BPCP displayed significantly denser fibrin networks with thinner fibers, higher porosity, and markedly faster coagulation times compared to BPCP. Mechanically, HF-BPCP exhibited greater stiffness, higher energy dissipation, and more stable adhesion, while almost eliminating scaffold retraction at 24 h. Despite improved early handling and structural integrity, HF-BPCP degraded more rapidly in vitro under tissue plasminogen activator exposure. GF release analysis showed reduced early peaks of platelet-derived factors (TGF-β1, PDGF-AB, VEGF) but sustained release thereafter, while extraplatelet factors (IGF-1, HGF) exhibited similar profiles between scaffolds. Conclusions: These results indicate that fibrinogen enrichment synergizes with the elevated extraplatelet protein profile of BPCP to enhance scaffold mechanical stability, handling properties, and controlled GF delivery. HF-BPCP combines the adhesive, structural, and bioactive features of fibrin sealants with the regenerative potential of PRP, offering a fully autologous alternative for clinical applications requiring rapid coagulation, high mechanical support, and sustained GF availability. Further preclinical and clinical studies are needed to evaluate therapeutic efficacy in the regenerative medicine field. Full article

Periodontal ligament stem cells (PDLSCs) represent a promising cell source for true periodontal regeneration due to their ability to form bone, cementum, and functional ligament. This review critically synthesised twelve in vivo studies (rats = 5, pigs = 2, dogs = 2, sheep = 2, one human trial) evaluating PDLSC transplantation for periodontal defects. A comprehensive search of PubMed, Web of Science, Embase, and the Cochrane Library (to May 2025) identified 358 records, of which 12 met predefined inclusion criteria. Data extraction encompassed cell source, scaffold, dose, follow-up, and quantitative regenerative outcomes. Nine studies reported cell doses (5 × 10⁵–2 × 10⁷ cells) and six PDLSC regeneration rates (33–100%). After normalisation for host mass, effective delivery ranged from 10⁵ to 10⁶ cells·kg⁻¹, with optimal outcomes typically above 10⁵ cells·kg⁻¹. PDLSC transplantation consistently enhanced alveolar bone, cementum, and periodontal-ligament regeneration compared with scaffold-alone or untreated controls, with the highest outcomes obtained using biocompatible scaffolds such as Hydroxyapatite/Tricalcium Phosphate (HA/TCP), Gelfoam, or amniotic membrane. Both autologous and allogeneic PDLSC achieved equivalent performance and excellent safety, while xenogeneic models confirmed immune tolerance. Despite encouraging results, the evidence remains preliminary—most studies were short-term and small-scale, and only one randomised human trial has been published. Standardisation of cell preparation, scaffold selection, dosing (absolute and mass-normalised), and follow-up is urgently needed. Future research should include Good Manufacturing Practice (GMP)-compliant clinical trials and mechanistic studies on PDLSC differentiation, paracrine signalling, and exosome-mediated effects to consolidate their translational potential for predictable periodontal regeneration. Full article

Background: Extensive skin injuries from severe burns or chronic non-healing ulcers overwhelm the body’s natural repair mechanisms, while current therapeutic approaches relying on autologous skin grafting are limited by donor site availability. Three-dimensional epithelial spheroid cultures enhance stem cell regenerative potential, but standardized comparative methodologies are lacking. Methods: We established a comprehensive framework comparing scaffold-free and scaffold-based epithelial spheroid systems using HaCaT keratinocytes. High-throughput approaches utilized BioFloat and ELPLASIA 96-well platforms, while low-throughput 6-well ULA plates generated heterogeneous populations (holospheres, merospheres, paraspheres). Scaffold-based studies embedded spheroids in Matrigel to evaluate outgrowth capacity. ROCK1 inhibitor treatment was assessed for stemness enhancement. Results: High-throughput systems generated uniform spheroids with high reproducibility and consistent circularity. Low-throughput cultures produced heterogeneous populations with distinct size distributions (holospheres: 408.7 μm², merospheres: 99 μm², paraspheres: 14.1 μm²). In Matrigel scaffolds, merospheres and paraspheres migrated outward, forming epithelial sheets, while holospheres remained intact as BMI-1+ stem cell reservoirs. ROCK1 inhibition enhanced holosphere formation, preserved stemness markers, and reduced premature differentiation. Conclusions: This standardized toolbox demonstrates scaffold-free systems optimize scalability for screening while scaffold-based approaches enable physiologically relevant regenerative studies. Integration of both methodologies provides flexibility matching experimental design to scientific objectives, accelerating translation to clinical applications. Full article

Regenerative endodontic approaches for immature necrotic permanent teeth must balance biological efficacy, clinical practicality and long-term aesthetic outcomes. This study evaluates a novel regenerative protocol using autologous advanced platelet-rich fibrin plus (A-PRF+) scaffold sealed exclusively with glass ionomer cement (GIC) and compares it to conventional calcium hydroxide apexification used as the control. Twenty-eight patients were prospectively enrolled and followed for 12 months alongside a retrospectively selected historical control group. Outcomes were evaluated through standardised blinded clinical, radiographic and vitality assessments. The A-PRF+ protocol demonstrated significantly faster periapical healing, superior root lengthening, increased dentinal wall thickness and apical closure (p < 0.0001), with excellent aesthetic outcomes and no reported tooth discolouration. Pulpal blood flow measured by laser Doppler flowmetry indicated vitality restoration in 93% of cases. Preliminary linear regression identified treatment duration as a significant predictor of apical closure (p < 0.0001), with possible enhancement by additional patient-specific variables. These findings validate the A-PRF+ protocol as a highly effective, aesthetically favourable and predictable regenerative strategy, establishing a new benchmark for the management of immature necrotic teeth and laying the foundation for personalised predictive endodontic care. Future studies should include multicentre randomised controlled trials to confirm long-term clinical sustainability and generalisability. Full article

Background: Spinal deformity correction surgery, particularly in scoliosis, often necessitates long fusion constructs and complex osteotomies that create significant structural bone defects. These defects threaten the integrity of spinal fusion, potentially compromising surgical outcomes. Bone grafting remains the cornerstone of addressing these defects, traditionally relying on autologous bone. However, limitations such as donor site morbidity and insufficient graft volume have made urgent the development and adoption of biologic substitutes and synthetic alternatives. Additionally, innovations in three-dimensional (3D) printing offer emerging solutions for graft customization and improved osseointegration. Objective: This scoping review maps the evidence of the effectiveness of the use of biologic and synthetic bone grafts in scoliosis surgery. It focusses on the role of novel technologies, particularly osteobiologics in combination with 3D-printed scaffolds, in enhancing graft performance and surgical outcomes. Methods: A comprehensive literature search was conducted using PubMed, Scopus, and the Cochrane Library to identify studies published within the last 15 years. Inclusion criteria focused on clinical and preclinical research involving biologic grafts (e.g., allografts, demineralized bone matrix-DBM, bone morphogenetic proteins-BMPs), synthetic substitutes (e.g., ceramics, polymers), and 3D-printed grafts in the context of scoliosis surgery. Data were extracted on graft type, clinical application, outcome measures, and complications. The review followed PRISMA-ScR guidelines and employed the Arksey and O’Malley methodological framework. Results: The included studies revealed diverse grafting strategies across pediatric and adult populations, with varying degrees of fusion success, incorporation rates, and complication profiles. It also included some anime studies. Emerging 3D technologies demonstrated promising preliminary results but require further validation. Conclusions: Osteobiologic and synthetic bone grafts, including those enhanced with 3D technologies, represent a growing area of interest in scoliosis surgery. Despite promising outcomes, more high-quality comparative clinical studies are needed to guide clinical decision-making and standardize practice. Full article

Cardiovascular diseases pose a significant global health burden, driving the need for artificial vascular grafts to address limitations of autologous and allogeneic vessels. This review examines the integration of fiber materials and textile technologies in vascular tissue engineering, focusing on structural mimicry and functional regeneration of native blood vessels. Traditional textile techniques (weaving, knitting, and braiding) and advanced methods (electrospinning, melt electrowriting, wet spinning, and gel spinning) enable the fabrication of fibrous scaffolds with hierarchical architectures resembling the extracellular matrix. The convergence of textile technology and fiber materials holds promise for next-generation grafts that integrate seamlessly with host tissue, addressing unmet clinical needs in vascular tissue regeneration. 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

This review article provides a comprehensive evaluation of Infuse^® and InductOs^®, two ground-breaking recombinant human Bone Morphogenetic Protein-2 (rhBMP-2)-based bone graft products, focusing on their tissue-level regenerative responses, clinical applications, and associated costs. Preclinical and clinical studies demonstrate that rhBMP-2 induces strong osteoinductive activity, effectively promoting mesenchymal stem cell differentiation and vascularized bone remodeling. While generally well-tolerated, these osteoinductive effects are dose-dependent, and excessive dosing or off-label use may result in adverse outcomes, such as ectopic bone formation or soft tissue inflammation. Histological and imaging analyses in craniofacial, orthopedic, and spinal fusion models confirm significant bone regeneration, positioning rhBMP-2 as a viable alternative to autologous grafts. Notably, advances in delivery systems and scaffold design have enhanced the stability, bioavailability, and targeted release of rhBMP-2, leading to improved fusion rates and reduced healing times in selected patient populations. These innovations, alongside its proven regenerative efficacy, underscore its potential to expand treatment options in cases where autografts are limited or unsuitable. However, the high initial cost, primarily driven by rhBMP-2, remains a critical limitation. Although some studies suggest overall treatment costs might be comparable to autografts when factoring in reduced complications and operative time, autografts often remain more cost-effective. Infuse^® has not substantially reduced the cost of bone regeneration and presents additional safety concerns due to the rapid (burst) release of growth factors and limited mechanical scaffold support. Despite representing a significant advancement in synthetic bone grafting, further innovation is essential to overcome limitations related to cost, mechanical properties, and controlled growth factor delivery. Full article

This scoping review aimed to systematically map the literature on digital workflows for the design and fabrication of customized bone grafts in oral and maxillofacial surgery. The review focused on the integration of cone-beam computed tomography (CBCT), computer-aided design (CAD), and computer-aided manufacturing (CAM) techniques for the production of personalized bone blocks. A systematic search of PubMed, Web of Science, and Ovid MEDLINE identified 151 records published between 2015 and 2025; after duplicate removal, screening, and full-text assessment, 16 articles were included. Six additional seminal studies published before 2015 were considered through manual search to provide historical background. The included studies consisted of case reports, case series, prospective clinical investigations, and preclinical experiments. Customization strategies involved synthetic hydroxyapatite scaffolds, CAD/CAM-milled allogeneic blocks, xenogeneic blocks, and digitally guided autogenous grafts. Four studies provided direct clinical documentation of customized CAD/CAM bone blocks, while the others offered complementary evidence on digital design, scaffold adaptation, or preclinical validation. Outcomes included graft adaptation, volumetric stability, implant survival, and limited histological analyses. Despite promising short-term results, no study has yet described the complete clinical workflow from CBCT acquisition to milling and implantation of a biological autologous or xenogeneic block in humans. This review underscores both the feasibility and the limitations of current approaches, highlighting the absence of fully validated digital-to-biological protocols as the main gap to be addressed in future research. Full article