Large bone defects caused by trauma, tumor resection, or congenital abnormalities remain a major clinical challenge. Standard titanium implants are widely used due to their strength and biocompatibility, but their bioinert surfaces often lead to poor osseointegration. The emergence of 3D printing has enabled patient-specific titanium implants with tailored architecture and mechanical properties. However, these constructs still lack the bioactivity required for robust and spatially uniform bone integration, particularly within the implant core. To address this limitation, we developed a bioactive, cell-free strategy that integrates porous titanium implants with a nanofibrillar peptide-hyaluronic acid scaffold, delivered either as a hydrogel or in lyophilized form. The scaffold exhibited enhanced enzymatic stability and supported osteoblast-like cell adhesion in vitro. In a rabbit calvarial critical-size bone defect model, scaffold-integrated implants significantly outperformed inert controls, with hydrogel integration nearly doubling inner bone volume and improving trabecular architecture. Histological analysis confirmed enhanced bone-implant integration, active periosteum, healthy marrow, and reduced inflammation. This acellular, growth-factor-free approach combines the structural precision of titanium with the regenerative potential of ECM-mimicking scaffolds, offering a translatable pathway for personalized skeletal repair.

Severe burn injuries represent a significant clinical challenge due to their complex healing process and the high risk of complications, including infection, scarring, and contracture formation. Current therapeutic approaches for burn wound treatment include autologous donor-site grafting and advanced cell therapy techniques like cultured epidermal autografts (CEA), which successfully facilitate wound closure through re-epithelialization. However, CEAs are limited by fragility, shrinkage, lack of a dermal layer, and risks of contamination. Here, aiming to overcome these limitations, this work develops a personalized skin equivalent featuring an engineered scaffold composed of electrospun poly(epsilon-caprolactone) (PCL) functionalized with the bioactive peptide fluorenylmethyloxycarbonyl-phenylalanine-arginine-glycine-aspartic acid (Fmoc-FRGD). This scaffold is designed to mimic the natural extracellular matrix (ECM), promoting cellular adhesion, integration, and proliferation while maintaining structural integrity. In vitro analysis demonstrated the scaffold's ability to support multi-layered human skin cell growth, while in vivo experiments confirmed its efficacy in facilitating wound closure and full-thickness skin regeneration in a murine model. This bioengineered skin equivalent is mechanically robust, easy to handle, fully autologous and exhibits no contraction, offering a transformative therapeutic alternative for the treatment of severe burn injuries.

Purpose. This pilot study aimed to explore the feasibility of scanning the human distal radius bone marrow in vivo to detect osteoporosis-related changes using magnetic resonance and evaluate whether the radius may serve as an accessible probing site for osteoporosis. This may lead in the future to the use of affordable means such as low-field MRI scanners for the monitoring of disease progression. Methods. A clinical trial was performed using a 3T MR scanner, including 26 women assigned into three study groups: healthy-premenopausal (n = 7; mean age 48.6 ± 3.5 years), healthy-postmenopausal (n = 10; mean age 54.5 ± 5.6 years), and osteoporotic-postmenopausal (n = 9; mean age 61.3 ± 5.6 years). Marrow fat composition was evaluated using T2 maps, a two-compartment model of T1, and a Dixon pulse sequence. Results. The osteoporotic group exhibited higher fat content than the other two groups and lower T2 values than the healthy-premenopausal group. Conclusions. Osteoporosis-related changes in the composition of the distal radius bone marrow may be detected in vivo using MRI protocols. The scanning protocols chosen here can later be repeated using low-field MRI scanners, thus offering the potential for early detection and treatment monitoring, using an accessible, affordable means that may be applied in small clinics. This trial is registered with MOH_2018-05-23_002247, NCT03742362.

Some cases of asymptomatic traumatic cyst can be sizable; therefore, they require complete curettage and grafting with bone substitution materials. This case report presents a sizeable traumatic mandibular cyst in a young man treated by surgical exploration and filled with autologous dentin graft (ADG) prepared from an extracted impacted tooth 48 (FDI tooth-numbering system) and advanced platelet-rich fibrin (A-PRF). Initially, an A-PRF membrane was used to cover the apices of teeth 42 and 43, which were protruding into the defect to protect their periapical structures. Then, a grafting strategy was introduced to achieve two fronts of bone formation: one by stimulation of bone outgrowth from the periphery due to A-PRF cellular activity, and a second by bone deposition directly on dentin particles in the center of the defect. On CBCT scans performed 7 months postoperatively, arrays of trabeculae that were extending from bone boundaries of the cyst defect were merged with more condensed bone deposited on ADG residuals in the center, thus filling the defect. It was found that autologous dentin combined with cellular A-PRF activity is a powerful tool to restore even sizable bone defects in a relatively short time frame with adequate bone remodeling.

AIM:To investigate the potential of an ultrashort aromatic peptide hydrogelator integrated with hyaluronic acid (HA) to serve as a scaffold for bone regeneration.MATERIALS AND METHODS:Fluorenylmethyloxycarbonyl-diphenylalanine (FmocFF)/HA hydrogel was prepared and characterized using microscopy and rheology. Osteogenic differentiation of MC3T3-E1 preosteoblasts was investigated using Alizarin red, alkaline phosphatase and calcium deposition assays. In vivo, 5-mm-diameter calvarial critical-sized defects were prepared in 20 Sprague-Dawley rats and filled with either FmocFF/HA hydrogel, deproteinized bovine bone mineral, FmocFF/Alginate hydrogel or left unfilled. Eight weeks after implantation, histology and micro-computed tomography analyses were performed. Immunohistochemistry was performed in six rats to assess the hydrogel's immunomodulatory effect.RESULTS:A nanofibrous FmocFF/HA hydrogel with a high storage modulus of 46 KPa was prepared. It supported osteogenic differentiation of MC3T3-E1 preosteoblasts and facilitated calcium deposition. In vivo, the hydrogel implantation resulted in approximately 93% bone restoration. It induced bone deposition not only around the margins, but also generated bony islets along the defect. Elongated M2 macrophages lining at the periosteum-hydrogel interface were observed 1 week after implantation. After 3 weeks, these macrophages were dispersed through the regenerating tissue surrounding the newly formed bone.CONCLUSIONS:FmocFF/HA hydrogel can serve as a cell-free, biomimetic, immunomodulatory scaffold for bone regeneration.

PURPOSE:There is little knowledge about healing patterns for the socket with an intentionally retained root fragment: a socket shield. The clinical observation is soft tissue ingrowth next to the socket shield. The aim of this study was to evaluate the effectiveness of autologous grafting matrices in preventing soft tissue ingrowth.MATERIALS AND METHODS:Patient data from a private clinic were searched for sockets with a socket shield left to heal with blood clot or grafted with autologous materials: autologous platelet-rich fibrin (PRF), scraped particulate bone, cortical tuberosity bone plate, or particulate dentin and covered with PRF membranes. The included sites were exposed by the flap 4 months after the first surgery, and soft tissue ingrowth depth and width next to the root fragment were measured by a scaled probe and documented.RESULTS:Evaluation of 34 sites showed the greatest depth of soft tissue ingrowth in the nongrafted sockets (6.0 ± 0.0 mm). Grafting with PRF plugs (depth of 2.3 ± 0.2 mm) or particulate bone (depth of 2.7 ± 0.6 mm) decreased soft tissue ingrowth. Grafting with particulate dentin or cortical tuberosity bone plate resulted in a soft tissue ingrowth depth of only 1 mm, yielding the best clinical outcome. Radiography confirmed those findings.CONCLUSION:Autologous dentin particulate or tuberosity cortical bone plate is most effective for preventing soft tissue ingrowth.

Mechanical loading through exercise builds bone strength, and this effect is most pronounced during skeletal growth and development. The cells that ultimately form or resorb bone may not necessarily be those that transduce signals in response to the applied mechanical loads. In cells sensitive to mechanical loads, mechanotransduction may involve signaling through mechanically activated ion channels in the cell membrane, focal adhesions of the cytoskeleton, or a G protein coupled mechanoreceptor. Extracellular adenosine-5’-triphosphate (ATP), through activation of purinoreceptors, initiates a cascade of signals, probably through Ca+2 fluxes, which propagate to the alveolar bone surface, stimulating osteoclastic bone resorption. Several reports showed that extracellular ATP can activate purinoreceptors in macrophages, stimulating their differentiation into osteoclasts. A treatment regimen that combines mechanical force with the separation of the gingival fibers from the root is capable of enhancing tissue remodeling and may lead to decreased root resorption of teeth undergoing OTM.

This study utilized radiographic comparative analysis in order to evaluate dimensional ridge changes four months after tooth extraction and immediate grafting with mineralized dentin particulate autograft and chopped platelet-rich fibrin. Fifty-eight extraction sockets with up to 2 mm of missing buccal bone in the coronal aspect compared to the lingual bone were included. Graft material was covered with either a platelet-rich fibrin membrane or collagen sponge with no effort to achieve primary closure. The dimensional changes of the ridge were assessed on cone-beam computed tomography (CBCT) images acquired prior to extraction and four months later. The reduction in the buccal bone plate thickness 1 mm, 3 mm, and 5 mm below the buccal crest was −0.87 ± 0.84 mm, −0.60 ± 0.70 mm, and −0.41 ± 0.55 mm, respectively. The mean ridge width changes 1 mm, 3 mm, and 5 mm below the crest were −1.38 ± 1.24 mm, −0.82 ± 1.13 mm, and −0.43 ± 0.89 mm, respectively. The average mid-buccal bone height gain was +1.1%, while the mid-lingual height gain was 5.6%. A mineralized dentin autograft with platelet-rich fibrin is effective in preserving post-extraction alveolar ridge dimensions.

This chapter aims to evaluate the influence of the grafted biomaterials on the cellular wound healing environment during the inflammatory and repair phases which culminate during the initial few weeks and the remodeling of the newly formed bone and the residual grafted biomaterial which may spread through several years. Three progressive phases of healing ensue after grafting surgery of an extraction site and bone defects, namely inflammatory phase, regenerative phase, and subsequent remodeling. The remodeling of the residual host alveolar bone, the regenerated engineered new tissues, and the grafted biomaterial are largely governed by changes in functional strains at the grafted site. In summary, the use of scaffolds for preserving or reconstructing the alveolar bone ridge became a frequent surgical procedure. It signifies the interaction between the scaffold biomaterial and the host innate immune response. The optimal scaffolding occurs, when the scaffold resorption is at the same pace as the newly deposited replacing bone.

Tooth extraction is one of the most widely performed procedures in dentistry, with more han 20 million extractions performed each year in the United States alone. Currently, extracted teeth are routinely discarded and considered clinical waste. Neverthless, wing to the bone-inducing potential of these mineralized tissues, more recently they have been ground to particulate graft material and utilized as bone grafting particles. ankylosed dentin and cementum undergo very slow remodelling by osteoclasts and are replaced by lamellar bone over time, thus offering a good solution to clinicians for minimizing dimensional changes after extraction by preserving the structure of the alveoloarridge. Based on clinical finding investigating ankylosed teeth, a dentin grinder was developed for a process in which freshly extracted teeth are ground in bacteria-free articulate autogenous mineralized dentin or immediate grafting. This process can be achieved within minutes and is indicated for a number of clinical scenarios when teeth are extracted. The freshly extracted tooth which most similar to the structure of autogenous cortical bone offers the type of graft that effectively promotes new bone formation in he first stages or wound healing and also supports and maintains the site with excellent long-term mechanical properties during the remodeling process. this chapter highlights the use of freshly prepared denting particles using a simple preparation protocol as an effective tool for alveoloar bone augmentation procedures that preserves the esthetics and function of the alveolar ridge following tooth extraction.

At present, attention is directed to increase the bone to implant contact (BIC) and minimize the marginal bone loss by modifying the root part of titanium implant using chemical and texture surface treatments. In the present review, we evaluate to what extent the titanium implant surface treatments are targeted to achieve biological attachment and connectivity similar to ankylosed teeth. We find that the re-implanted tooth that undergoes ankylosis to alveolar bone and re-attachment of marginal gingiva by cellular and fibrous biological connectivity is a desirable model to seek similar implant attachment to the periodontium. In fact, the root part of the implant that is undergoing osseointegration resembles direct deposition of bone onto tooth cementum. It seems that activating cellular attachment of soft connective tissue of marginal gingiva is less predictable and needs the application of nano technologies to enhance attraction of these cells to the trans-gingival connector. Such cellular physiologically strained attachment will develop normal communicative pathways between implant and periodontium. This paper provides a new perspective on the model that should guide the development of future dental implants. Surface modifications of implants should facilitate their attachment both to the alveolar bone and the marginal gingiva, mimicking the physiological process involved in re-implanted teeth.

Following tooth extraction, we often observe significant changes of ridge contour that is the result of alveolar bone loss. Most of the bone loss occurs during the first 3 to 4 months following extraction. To prevent this, it is strongly recommended to graft the extraction site with a biocompatible and bioactive osseous graft material at the time of extraction. There are many options available for socket grafting each with its own deficiencies. Most of the synthetic and allograft type bone substitutes preserve the alveolar ridge during the repair phase of the wound healing, but subsequently resorb during the following remodeling phase and therefore only achieve partial ridge restoration. Xenografts, on the contrary, do not osseointegrate sufficiently and form “islands” of foreign body within the bone structure. Recently, a novel procedure was developed where the extracted tooth is immediately processed into an autologous graft that preserves the alveolar ridge for many years and is biocompatible to the host site in a highly predictable manner. The procedure also helps to keep treatment costs lower than prepackaged graft materials. This autologous dentin particulate, made from the extracted tooth of the patient, undergoes ankylosis with the newly formed bone around it. The result is a biological connection or fusion of the graft and the host bone, an interface that is more biological than other alternatives, hence providing optimal and predictable results in the short and long term.

Following tooth extraction, we often observe significant changes of ridge contour that is the result of alveolar bone loss.Most of the bone loss occurs during the first 3 to 4 months following extraction.To prevent this, it is strongly recommended to graft the extraction site with a biocompatible and bioactive osseous graft material at the time of extraction.There are many options available for socket grafting each with its own deficiencies.Most of the synthetic and allograft type bone substitutes preserve the alveolar ridge during the repair phase of the wound healing, but subsequently resorb during the following remodeling phase and therefore only achieve partial ridge restoration.Xenografts, on the contrary, do not osseointegrate sufficiently and form "islands" of foreign body within the bone structure.Recently, a novel procedure was developed where the extracted tooth is immediately processed into an autologous graft that preserves the alveolar ridge for many years and is biocompatible to the host site in a highly predictable manner.The procedure also helps to keep treatment costs lower than prepackaged graft materials.This autologous dentin particulate, made from the extracted tooth of the patient, undergoes ankylosis with the newly formed bone around it.The result is a biological connection or fusion of the graft and the host bone, an interface that is more biological than other alternatives, hence providing optimal and predictable results in the short and long term.

Periodontal diseases are initiated by pathogenic bacterial biofilm activity that induces a host inflammatory cells immune response, degradation of dento gingival fibrous tissue and its detachment from root cementum. It is well accepted, that osteoclastic alveolar bone loss is governed exclusively through secretion of proinflammatory cytokines. Nevertheless, our findings suggest that once degradation of collagen fibers by MMPs occurs, a drop of cellular strains cause immediate release of ATP from marginal gingival fibroblasts, cell deformation and influx of Ca+2. Increased extracellular ATP (eATP) by interacting with P2×7 purinoreceptors, present on fibroblasts and osteoblasts, induces generation of receptor activator of nuclear factor kB ligand (RANKL) that further activates osteoclastic alveolar bone resorption and bone loss. In addition, increased eATP levels may amplify inflammation by promoting leukocyte recruitment and NALP3-inflammasome activation via P2×7. Then, the inflammatory cells secrete cytokines, interleukin IL-1, TNF and RANKL that further trigger alveolar bone resorption. Moreover, eATP can be secreted from periodontal bacteria that may further contribute to inflammation and bone loss in periodontitis. It seems therefore, that eATP is a key modulator that initiates the pathway of alveolar bone resorption and bone loss in patients with periodontal disease. In conclusion, we propose that strain release in gingival fibroblasts aligned on collagen fibers, due to activity of MMP, activates release of ATP that triggers the pathway of alveolar bone resorption in periodontitis. We predict that by controlling the eATP interaction with its cellular purinoreceptors will reduce significantly bone loss in periodontitis.

The healing process of a tooth extraction site results in significant changes of alveolar ridge contour caused by alveolar bone loss, most of it, during 3-4 months after extraction. It is therefore strongly indicated to graft the extracted site with biocompatible or bioactive bone grafts. Most of the synthetic allogeneic and xenografts preserve the alveolar ridge during the repair phase and then it resorbs during the remodeling phase, thus, achieving only a partial ridge restoration. In recent years, a novel procedure was developed where the extracted tooth is transformed into immediate graft that preserves best the alveolar ridge for many years. This happens because the autologous dentin undergoes ankyloses with newly formed bone thatis biologically connected to the host bone this way restoring a functional connectivity between host bone and dentin particles.

Osteoporosis is characterized by reduction in trabecular bone in conjunction with increased marrow cell adiposity. While these changes occur within weeks, monitoring of treatment efficacy as performed by DEXA is sensitive only to long-term changes. MRI is sensitive to bone marrow changes but is less affordable. In a recent study, we have shown that a stray-field NMR can monitor bone marrow cellular changes that are related to osteoporosis. Objectives. To demonstrate sensitivity of a low-field tabletop NMR scanner to bone marrow dynamics following hormonal treatment in rats. Methods. Two-month-old female rats (n = 36) were ovariectomized (OVX) and dosed for the ensuing 3 or 5 weeks with 20 mg/kg of PTH(1-34). Hind limbs femurs and tibiae were isolated and underwent ex vivo microradiography and histology and NMR relaxometry at 6 weeks (preventive experiment) and 11 weeks (therapeutic treatment experiment) after OVX. Results. OVX rats developed osteoporotic changes including adipogenic marrow compared to Sham and PTH treated rats. T2 and ADC NMR relaxation coefficients were found to correlate with marrow composition. Conclusions. This study suggests that stray-field NMR, an affordable method that is sensitive to the rapid cellular changes in bone marrow, may have a clinical value in monitoring hormonal treatment for osteoporosis.

PurposeOsteoporosis is characterized by a decrease in bone mineral density (BMD). A preliminary stage of the disease is progressive bone marrow adiposity, caused by imbalance between osteogenesis and adipogenesis in the marrow. Detection of osteoporosis relies on the quantification of BMD with techniques such as dual‐energy X‐ray absorptiometry. This work aimed to detect bone marrow changes in an experimental model of osteopenia using a low‐field tabletop NMR scanner.MethodsAn experiment was performed on 32 female rats, 3 months old, 16 of which were ovariectomized (OVX) and 16 were sham‐operated (sham). The femur and tibia from both hind limbs were isolated and underwent ex vivo NMR scans at four time points after the OVX and sham operations. NMR scans were complemented by BMD measurements and histology.ResultsSignificant changes in the bone marrow of ovariectomized rats, relative to sham operated rats, were observed after 3.5 and 4.5 months. Bone marrow adiposity was detected by significant changes in T1 and T2 relaxation times, and in the diffusion coefficient.ConclusionsThis study suggests a potential detection of changes to the bone marrow using a tabletop NMR device. Clinical translation may facilitate screening, early detection of bone weakening as a result of estrogen withdrawal, and monitoring of treatment efficacy. Magn Reson Med 78:860–870, 2017. © 2016 International Society for Magnetic Resonance in Medicine.