Gli1+ Periodontal Mesenchymal Stem Cells in Periodontitis.

Periodontal mesenchymal stem cells (MSCs) play a crucial role in maintaining periodontium homeostasis and in tissue repair. However, little is known about how periodontal MSCs in vivo respond under periodontal disease conditions, posing a challenge for periodontium tissue regeneration. In this study, Gli1 was used as a periodontal MSC marker and combined with a Gli1-cre ERT2 mouse model for lineage tracing to investigate periodontal MSC fate in an induced periodontitis model. Our findings show significant changes in the number and contribution of Gli1+ MSCs within the inflamed periodontium. The number of Gli1+ MSCs that contributed to periodontal ligament homeostasis decreased in the periodontitis-induced teeth. While the proliferation of Gli1+ MSCs had no significant difference between the periodontitis and the control groups, more Gli1+ MSCs underwent apoptosis in diseased teeth. In addition, the number of Gli1+ MSCs for osteogenic differentiation decreased during the progression of periodontitis. Following tooth extraction, the contribution of Gli1+ MSCs to the tooth socket repair was significantly reduced in the periodontitis-induced teeth. Collectively, these findings indicate that the function of Gli1+ MSCs in periodontitis was compromised, including reduced contribution to periodontium homeostasis and impaired injury response.

Advances Focusing on the Application of Decellularized Extracellular Matrix in Periodontal Regeneration.

The decellularized extracellular matrix (dECM) is capable of promoting stem cell proliferation, migration, adhesion, and differentiation. It is a promising biomaterial for application and clinical translation in the field of periodontal tissue engineering as it most effectively preserves the complex array of ECM components as they are in native tissue, providing ideal cues for regeneration and repair of damaged periodontal tissue. dECMs of different origins have different advantages and characteristics in promoting the regeneration of periodontal tissue. dECM can be used directly or dissolved in liquid for better flowability. Multiple ways were developed to improve the mechanical strength of dECM, such as functionalized scaffolds with cells that harvest scaffold-supported dECM through decellularization or crosslinked soluble dECM that can form injectable hydrogels for periodontal tissue repair. dECM has found recent success in many periodontal regeneration and repair therapies. This review focuses on the repairing effect of dECM in periodontal tissue engineering, with variations in cell/tissue sources, and specifically discusses the future trend of periodontal regeneration and the future role of soluble dECM in entire periodontal tissue regeneration.

Dental Follicle Stem Cells Promote Periodontal Regeneration through Periostin-Mediated Macrophage Infiltration and Reprogramming in an Inflammatory Microenvironment.

Dental follicle stem cells (DFSCs) have been verified to promote periodontal regeneration in an inflammatory microenvironment. When coping with inflammatory stimulation, DFSCs highly express periostin, a bioactive molecule closely related to periodontal homeostasis. It is worth exploring whether and how periostin plays a role in the promotion of periodontal regeneration by DFSCs. By tracking the fate of DFSCs, it was found that DFSCs significantly contributed to periodontal regeneration in rat periodontal defects while they had a low survival rate. They highly expressed periostin and improved the immune microenvironment in the defect area, especially via the recruitment and reprogramming of macrophages. Silencing periostin attenuated the effects of DFSCs in promoting periodontal regeneration and regulating macrophages. Recombinant human periostin (rhPeriostin) could not only directly promote macrophage reprogramming through the integrin αM/phosphorylated extracellular signal-regulated kinase (p-Erk)/Erk signaling pathway, but it also exhibited the potential to promote periodontal regeneration in rats when loaded in a collagen matrix. These results indicated that periostin is actively involved in the process by which DFSCs promote periodontal regeneration through the regulation of macrophages and is a promising molecular agent to promote periodontal regeneration. This study provides new insight into the mechanism by which DFSCs promote periodontal regeneration and suggests a new approach for periodontal regeneration therapy.

Immunomodulatory nanotherapeutic approaches for periodontal tissue regeneration.

Periodontitis is an infection-induced inflammatory disease characterized by progressive destruction of tooth supporting tissues, which, if left untreated, can result in tooth loss. The destruction of periodontal tissues is primarily caused by an imbalance between the host immune protection and immune destruction mechanisms. The ultimate goal of periodontal therapy is to eliminate inflammation and promote the repair and regeneration of both hard and soft tissues, so as to restore the physiological structure and function of periodontium. Advancement in nanotechnologies has enabled the development of nanomaterials with immunomodulatory properties for regenerative dentistry. This review discusses the immune mechanisms of the major effector cells in the innate and adaptive immune systems, the physicochemical and biological properties of nanomaterials, and the research advancements in immunomodulatory nanotherapeutic approaches for the management of periodontitis and the regeneration of periodontal tissues. The current challenges, and prospects for future applications of nanomaterials are then discussed so that researchers at the intersections of osteoimmunology, regenerative dentistry and materiobiology will continue to advance the development of nanomaterials for improved periodontal tissue regeneration.

Epigenetic regulation of dental-derived stem cells and their application in pulp and periodontal regeneration.

Dental-derived stem cells have excellent proliferation ability and multi-directional differentiation potential, making them an important research target in tissue engineering. An increasing number of dental-derived stem cells have been discovered recently, including dental pulp stem cells (DPSCs), stem cells from exfoliated deciduous teeth (SHEDs), stem cells from apical papilla (SCAPs), dental follicle precursor cells (DFPCs), and periodontal ligament stem cells (PDLSCs). These stem cells have significant application prospects in tissue regeneration because they are found in an abundance of sources, and they have good biocompatibility and are highly effective. The biological functions of dental-derived stem cells are regulated in many ways. Epigenetic regulation means changing the expression level and function of a gene without changing its sequence. Epigenetic regulation is involved in many biological processes, such as embryonic development, bone homeostasis, and the fate of stem cells. Existing studies have shown that dental-derived stem cells are also regulated by epigenetic modifications. Pulp and periodontal regeneration refers to the practice of replacing damaged pulp and periodontal tissue and restoring the tissue structure and function under normal physiological conditions. This treatment has better therapeutic effects than traditional treatments. This article reviews the recent research on the mechanism of epigenetic regulation of dental-derived stem cells, and the core issues surrounding the practical application and future use of pulp and periodontal regeneration.

CHANGES IN THE ULTRASTRUCTURAL ELEMENTS OF PERIODONTAL NEUROTROPHY UNDER CONDITIONS OF ACUTE SIMPLE COAGULATION DYSTROPHY IN THE EXPERIMENT.

OBJECTIVE: Aim: To determine the role of damage to the ultrastructural elements of the periodontal nervous system in the pathogenesis of dystrophic periodontal disease. PATIENTS AND METHODS: Materials and Methods: The basis of the experimental part of the study was the preparation of ultrathin sections from blocks of gum tissue of white rats, which were prepared using the UMTP-3M device. The study and analysis of biopsy samples was carried out with the help of an electron microscope UEMV-100K. RESULTS: Results: With the help of transmission electron microscopy, it was found that from the first minutes after the injection of hemolysate of isogenic erythrocytes into the rats, aggregates of erythrocytes, clumps of blood plasma, clusters of fibrin monomer masses, bundles of fibrin fibers, platelet and homogeneous were present in the connective tissue of the gums, and in particular in the lumens of hemocapillaries microthrombi, which confirms damage to the ultrastructures of the periodontium, which lead to the development of a pathological process, which is described when simple coagulation dystrophy is reproduced. CONCLUSION: Conclusions: Coagulative damage to the ultrastructural elements of the periodontal nervous system is one of the important factors in the pathogenesis of dystrophic periodontal damage. Under these conditions, trophic disturbances occur, similar to those that occur when the integrity of the nerve is disturbed - neurotrophic mechanism of dystrophy.

Neural Regulations in Tooth Development and Tooth-Periodontium Complex Homeostasis: A Literature Review.

The tooth-periodontium complex and its nerves have active reciprocal regulation during development and homeostasis. These effects are predominantly mediated by a range of molecules secreted from either the nervous system or the tooth-periodontium complex. Different strategies mimicking tooth development or physiological reparation have been applied to tooth regeneration studies, where the application of these nerve- or tooth-derived molecules has been proven effective. However, to date, basic studies in this field leave many vacancies to be filled. This literature review summarizes the recent advances in the basic studies on neural responses and regulation during tooth-periodontium development and homeostasis and points out some research gaps to instruct future studies. Deepening our understanding of the underlying mechanisms of tooth development and diseases will provide more clues for tooth regeneration.

A Biomimetic Smart Nanoplatform as "Inflammation Scavenger" for Regenerative Therapy of Periodontal Tissue.

Introduction: The functional reconstruction of periodontal tissue defects remains a clinical challenge due to excessive and prolonged host response to various endogenous and exogenous pro-inflammatory stimuli. Thus, a biomimetic nanoplatform with the capability of modulating inflammatory response in a microenvironment-responsive manner is attractive for regenerative therapy of periodontal tissue. Methods: Herein, a facile and green design of engineered bone graft materials was developed by integrating a biomimetic apatite nanocomposite with a smart-release coating, which could realize inflammatory modulation by "on-demand" delivery of the anti-inflammatory agent through a pH-sensing mechanism. Results: In vitro and in vivo experiments demonstrated that this biocompatible nanoplatform could facilitate the clearance of reactive oxygen species in human periodontal ligament stem cells under inflammatory conditions via inhibiting the production of endogenous proinflammatory mediators, in turn contributing to the enhanced healing efficacy of periodontal tissue. Moreover, this system exhibited effective antimicrobial activity against common pathogenic bacteria in the oral cavity, which is beneficial for the elimination of exogenous pro-inflammatory factors from bacterial infection during healing of periodontal tissue. Conclusion: The proposed strategy provides a versatile apatite nanocomposite as a promising "inflammation scavenger" and propels the development of intelligent bone graft materials for periodontal and orthopedic applications.

Novel approaches for periodontal tissue engineering.

The periodontal complex involves the hard and soft tissues which support dentition, comprised of cementum, bone, and the periodontal ligament (PDL). Periodontitis, a prevalent infectious disease of the periodontium, threatens the integrity of these tissues and causes irreversible damage. Periodontal therapy aims to repair and ultimately regenerate these tissues toward preserving native dentition and improving the physiologic integration of dental implants. The PDL contains multipotent stem cells, which have a robust capacity to differentiate into various types of cells to form the PDL, cementum, and alveolar bone. Selection of appropriate growth factors and biomaterial matrices to facilitate periodontal regeneration are critical to recapitulate the physiologic organization and function of the periodontal complex. Herein, we discuss the current state of clinical periodontal regeneration including a review of FDA-approved growth factors. We will highlight advances in preclinical research toward identifying additional growth factors capable of robust repair and biomaterial matrices to augment regeneration similarly and synergistically, ultimately improving periodontal regeneration's predictability and long-term efficacy. This review should improve the readers' understanding of the molecular and cellular processes involving periodontal regeneration essential for designing comprehensive therapeutic approaches.

Development and regeneration of periodontal supporting tissues.

Periodontal tissues, including gingiva, cementum, periodontal ligament, and alveolar bone, play important roles in oral health. Under physiological conditions, periodontal tissues surround and support the teeth, maintaining the stability of the teeth and distributing the chewing forces. However, under pathological conditions, with the actions of various pathogenic factors, the periodontal tissues gradually undergo some irreversible changes, that is, gingival recession, periodontal ligament rupture, periodontal pocket formation, alveolar bone resorption, eventually leading to the loosening and even loss of the teeth. Currently, the regenerations of the periodontal tissues are still challenging. Therefore, it is necessary to study the development of the periodontal tissues, the principles and processes of which can be used to develop new strategies for the regeneration of periodontal tissues. This review summarizes the development of periodontal tissues and current strategies for periodontal healing and regeneration.

Multicompartmental Scaffolds for Coordinated Periodontal Tissue Engineering.

Successful periodontal repair and regeneration requires the coordinated responses from soft and hard tissues as well as the soft tissue-to-bone interfaces. Inspired by the hierarchical structure of native periodontal tissues, tissue engineering technology provides unique opportunities to coordinate multiple cell types into scaffolds that mimic the natural periodontal structure in vitro. In this study, we designed and fabricated highly ordered multicompartmental scaffolds by melt electrowriting, an advanced 3-dimensional (3D) printing technique. This strategy attempted to mimic the characteristic periodontal microenvironment through multicompartmental constructs comprising 3 tissue-specific regions: 1) a bone compartment with dense mesh structure, 2) a ligament compartment mimicking the highly aligned periodontal ligaments (PDLs), and 3) a transition region that bridges the bone and ligament, a critical feature that differentiates this system from mono- or bicompartmental alternatives. The multicompartmental constructs successfully achieved coordinated proliferation and differentiation of multiple cell types in vitro within short time, including both ligamentous- and bone-derived cells. Long-term 3D coculture of primary human osteoblasts and PDL fibroblasts led to a mineral gradient from calcified to uncalcified regions with PDL-like insertions within the transition region, an effect that is challenging to achieve with mono- or bicompartmental platforms. This process effectively recapitulates the key feature of interfacial tissues in periodontium. Collectively, this tissue-engineered approach offers a fundament for engineering periodontal tissue constructs with characteristic 3D microenvironments similar to native tissues. This multicompartmental 3D printing approach is also highly compatible with the design of next-generation scaffolds, with both highly adjustable compartmentalization properties and patient-specific shapes, for multitissue engineering in complex periodontal defects.

Titanium Nanosurface with a Biomimetic Physical Microenvironment to Induce Endogenous Regeneration of the Periodontium.

The periodontium supports the teeth by dentoalveolar fibrous joints that serve unique oral functions. Endogenous regeneration of the periodontium around artificial teeth (dental implants) provides a cost-effective solution for the extension of healthy life expectancy but remains a challenge in regenerative medicine. Biomimetics can create smart biomaterials that tune endogenous cells at a tissue-material interface. Here, we created a smart titanium nanosurface mimicking the surface nanotopography and micromechanical properties of the tooth root cementum (TRC), which is essential for the induction of dentoalveolar fibrous joints to regenerate the periodontium. After transplantation into the rat renal capsule, only the titanium artificial tooth with the TRC-mimetic nanosurface formed a complex dentoalveolar fibrous joint structure, with bone tissue, periodontal ligament (PDL), and TRC, in the decellularized jawbone matrix. TRC-mimetic titanium implants induce the formation of functional periodontium, even in a jawbone implantation model, which generally causes osseointegration (ankyloses). In human PDL cells, TRC analogousness in the surface mechanical microenvironment regulates matrix mineralization through bone sialoprotein expression and phosphorus metabolism, which are critical for cementogenesis. Therefore, the titanium nanosurfaces with nanotopographical and mechanical microenvironments mimicking the TRC surface induce dentoalveolar fibrous joints for periodontal regeneration by interfacial tuning of endogenous cells.

Molecular Research on Oral Diseases and Related Biomaterials: A Journey from Oral Cell Models to Advanced Regenerative Perspectives.

Oral diseases such as gingivitis, periodontitis, and oral cancer affect millions of people worldwide. Much research has been conducted to understand the pathogenetic mechanisms of these diseases and translate this knowledge into therapeutics. This review aims to take the reader on a journey from the initial molecular discoveries to complex regenerative issues in oral medicine. For this, a semi-systematic literature search was carried out in Medline and Web of Science databases to retrieve the primary literature describing oral cell models and biomaterial applications in oral regenerative medicine. First, an in vitro cell model of gingival keratinocytes is discussed, which illustrates patho- and physiologic principles in the context of oral epithelial homeostasis and carcinogenesis and represents a cellular tool to understand biomaterial-based approaches for periodontal tissue regeneration. Consequently, a layered gradient nonwoven (LGN) is described, which demonstrates that the key features of biomaterials serve as candidates for oral tissue regeneration. LGN supports proper tissue formation and obeys the important principles for molecular mechanotransduction. Furthermore, current biomaterial-based tissue regeneration trends, including polymer modifications, cell-based treatments, antimicrobial peptides and optogenetics, are introduced to represent the full spectrum of current approaches to oral disease mitigation and prevention. Altogether, this review is a foray through established and new concepts in oral regenerative medicine and illustrates the process of knowledge translation from basic molecular and cell biological research to future clinical applications.

Periodontal Cell Therapy: A Systematic Review and Meta-analysis.

BACKGROUND: Periodontitis is a chronic inflammatory disease characterized by the loss of tooth-supporting tissues (or periodontium) leading to the formation of periodontal pocket then to tooth loss. Conventional therapies that involve tooth root debridement are still disappointing because they are more centered on periodontal repair than disease pathophysiology causes. The meta-analysis we present here focused on the results of experimental studies that investigated periodontal mesenchymal stromal cells (MSCs) therapy, a promising strategy to regenerate tissue, given to their immunomodulatory and trophic properties. METHODS: Using PubMed database and ICTRP search portal, 84 animal and 3 randomized human studies were analyzed. RESULTS: Overall, our results highlighted that MSCs grafting, regardless of their tissue origin, enhances periodontal regeneration. A defect morphology suitable for an initial clot stabilization increases the procedure efficacy, especially if cells are carried using a vehicle from natural origin. Nevertheless, methodological biases have been highlighted and still limit the translation to human with high prognosis and regulatory considerations. Besides, because only 2 randomized human trials demonstrated the efficacy of the procedure, further studies are needed to investigate periodontal regeneration procedures on experimental models closer to human pathophysiology. CONCLUSION: Although MSCs grafting in periodontal disease demonstrated therapeutic benefits in animal, it is critical to define more accurately protocols translatable to human and focus on the treatment of the pathology as a whole rather than on the restitution of the sole destroyed tissues.

Between a rock and a hard place: Regulation of mineralization in the periodontium.

The periodontium supports and attaches teeth via mineralized and nonmineralized tissues. It consists of two, unique mineralized tissues, cementum and alveolar bone. In between these tissues, lies an unmineralized, fibrous periodontal ligament (PDL), which distributes occlusal forces, nourishes and invests teeth, and harbors progenitor cells for dentoalveolar repair. Many unanswered questions remain regarding periodontal biology. This review will focus on recent research providing insights into one enduring mystery: the precise regulation of the hard-soft tissue borders in the periodontium which define the interfaces of the cementum-PDL-alveolar bone structure. We will focus on advances in understanding the molecular mechanisms that maintain the unmineralized PDL "between a rock and a hard place" by regulating the mineralization of cementum and alveolar bone.

Stem Cell Transplantation and Cell-Free Treatment for Periodontal Regeneration.

Increasing attention has been paid to cell-based medicines. Many in vivo and in vitro studies have demonstrated the efficacy of stem cell transplantation for the regeneration of periodontal tissues over the past 20 years. Although positive evidence has accumulated regarding periodontal regeneration using stem cells, the exact mechanism of tissue regeneration is still largely unknown. This review outlines the practicality and emerging problems of stem cell transplantation therapy for periodontal regeneration. In addition, possible solutions to these problems and cell-free treatment are discussed.

Compression loading of osteoclasts attenuated microRNA-146a-5p expression, which promotes angiogenesis by targeting adiponectin.

Osteoclastogenesis in alveolar bone induced by compression stress triggers orthodontic tooth movement. Compression stress also stimulates angiogenesis, which is essential for osteoclastogenesis. However, the effects of osteoclastogenesis induced by compression on angiogenesis are poorly understood. In vivo, we found the markers of angiogenesis increased during orthodontic bone remodeling. In vitro, osteoclast-derived exosomes increased proliferation, migration, and tube formation of human umbilical vein endothelial cells (HUVECs), as well as expression of vascular endothelial growth factor and CD31. The promotive effects of exosomes derived from compressed osteoclasts were greater than those derived from osteoclasts without compression. Next, we analyzed changes in the microRNA transcriptome after compression stress and focused on microRNA146a-5p (miR-146a), which was significantly decreased by compression. Transfection of an inhibitor of miR-146a stimulated angiogenesis of HUVECs while miR-146a mimics repressed angiogenesis. Adiponectin (ADP) was confirmed to be a target of miR-146a by dual luciferase reporter assay. In HUVECs treated with exosomes, we detected increased ADP which promoted angiogenesis. Knockdown of ADP in HUVECs reduced the promotive effects of exosomes. Our results demonstrate that the decreased miR-146a observed in osteoclasts after compression promotes angiogenesis by targeting ADP, suggesting a novel method to interfere with bone remodeling induced by compression stress.

Preparation and characterization of poly (lactic-co-glycolic acid) nanofibers containing simvastatin coated with hyaluronic acid for using in periodontal tissue engineering.

Periodontal diseases can lead to soft tissue defects. Tissue engineering can provide functional replacements for damaged tissues. Recently, electrospun nanofibers have attracted great interest for tissue engineering and drug delivery applications. This has been revealed that statins exhibit positive impacts on the proliferation and regeneration of periodontal tissues. Electrospun simvastatin loaded poly (lactic-co-glycolic acid) (SIM-PLGA-NF) were prepared using electrospinning technique. Optimal conditions for preparation of SIM-PLGA-NF (PLGA concentration of 30 wt%, voltage of 15 kV, and flow rate of 1.5 ml h-1 ) were identified using a 23 factorial design. The optimized SIM-PLGA-NFs (diameter of 640.2 ± 32.5 nm and simvastatin entrapment efficacy of 99.6 ± 1.5%) were surface modified with 1% w/v hyaluronic acid solution (1%HA- SIM-PLGA-NF) to improve their compatibility with fibroblasts and potential application as a periodontal tissue engineering scaffold. HA-SIM-PLGA NFs were analyzed using SEM, FTIR, and XRD. 1%HA-SIM-PLGA-NF had uniform, bead-free and interwoven morphology, which is similar to the extracellular matrix. The mechanical performance of SIM-PLGA-NFs and release profile of simvastatin from these nanofibers have been also greatly improved after coating with HA. In vitro cellular tests showed that the proliferation, adhesion, and differentiation of fibroblast cells positively enhanced on the surface of 1%HA- SIM-PLGA-NF. These results demonstrate the potential application of 1%HA-SIM-PLGA-NFs as a scaffold for periodontal tissue engineering.

Assessment of the effect of vacuum-formed retainers and Hawley retainers on periodontal health: A systematic review and meta-analysis.

BACKGROUND: Recently, increasing attention has been paid to the periodontal health of orthodontic patients in the maintenance stage in clinical practice. The focus of this meta-analysis was to compare the effects of vacuum-formed retainers (VFR) and Hawley retainers (HR) on periodontal health, in order to provide a reference for clinical selection. METHODS: From the establishment of the database until November 2020, a large number of databases were searched to find relevant randomized control trials, including the Cochrane Library databases, Embase, PubMed, Medline via Ovi, Web of Science, Scopus, Grey Literature in Europe, Google Scholar and CNKI. Related literature was manually searched and included in the analysis. Two researchers screened the literature according to relevant criteria. The size of the effect was determined using RevMan5.3 software, and the mean difference and 95% confidence intervals (CI) were used to estimate the results using a random effects model. RESULTS: This meta-analysis included six randomized controlled trials involving 304 patients. The results of the meta-analysis showed that there was no statistical difference in sulcus probing depth status between the VFR group and the HR group, including at 1, 3, and 6 months. Compared with the VFR group, the HR group showed a lower gingival index at 1 month (mean difference = 0.12, 95%CI: 0.06 to 0.19) and 3 months (mean difference = 0.11, 95%CI: 0.06 to 0.17), while there was no statistically significant difference at 6 months (mean difference = 0.10, 95%CI: -0.07 to 0.27). The plaque index of the HR group also showed a good state at 1 month (mean difference = 0.06, 95%CI: 0.01 to 0.12), 3 months (mean difference = 0.12, 95%CI: 0.08 to 0.16), and 6 months (mean difference = 0.19, 95%CI: 0.09 to 0.29). Subgroup analysis of PLI showed that when all teeth were measured, PLI status was lower in the HR group at 6 months (mean difference = 0.32, 95%CI: 0.18 to 0.46). PLI status was also low for the other teeth group (mean difference = 0.15, 95%CI: 0.08 to 0.22). CONCLUSION: Our meta-analysis showed that patients using the Hawley retainer had better periodontal health compared with those using vacuum-formed retainers. However, more research is needed to look at the periodontal health of patients using these two retainers.

Aptamers recognizing fibronectin confer improved bioactivity to biomaterials and promote new bone formation in a periodontal defect in rats.

The use of alloplastic materials in periodontal regenerative therapies is limited by their incapacity to establish a dynamic dialog with the surrounding milieu. The aim of the present study was to control biomaterial surface bioactivity by introducing aptamers to induce the selective adsorption of fibronectin from blood, thus promoting platelets activation in vitro and bone regeneration in vivo. A hyaluronic acid/polyethyleneglycole-based hydrogel was enriched with aptamers selected for recognizing and binding fibronectin. In vitro, the capacity of constructs to support osteoblast adhesion, as well as platelets aggregation and activation was assessed by chemiluminescence within 24 h. Matrices were then evaluated in a rat periodontal defect to assess their regenerative potential by microcomputed tomography (µCT) and their osteogenic capacity by Luminex assay 5, 15 and 30 d postoperatively. Aptamers were found to confer matrices the capacity of sustaining firm cell adhesion (p = 0.0377) and to promote platelets activation (p = 0.0442). In vivo, aptamers promoted new bone formation 30 d post-operatively (p < 0.001) by enhancing osteoblastic lineage commitment maturation. Aptamers are a viable surface modification, which confers alloplastic materials the potential capacity to orchestrate blood clot formation, thus controlling bone healing.