Natural Healing Research Articles

Bioactive Biosilicate Cements in Pediatric Dentistry – A Review of the Latest Materials

ABSTRACT Pediatric dentistry plays a critical role in ensuring the oral health and well-being of children and adolescents. The quest for effective dental materials that are safe, biocompatible, and capable of promoting natural remineralization has led to the emergence of biosilicate cements as a promising advancement in this field. Biosilicate cements are bioactive materials composed of amorphous silica, calcium oxide, phosphorus pentoxide, and other trace elements. The bioactivity of biosilicate cements allows them to interact with living tissues, promoting remineralization and stimulating the formation of hydroxyapatite, a vital component of teeth and bones. Their ability to release essential ions, such as calcium, phosphate, and fluoride, supports the natural healing processes, aiding in the preservation of pulp vitality and reducing the risk of secondary caries. Biosilicate cements offer versatility in pediatric dentistry, finding application indirect pulp capping, indirect pulp capping, and small-sized restorations. Their rapid setting time proves advantageous when treating young patients with limited cooperation. Furthermore, the continuous release of fluoride contributes to caries prevention and enhances the long-term oral health of children. While the advantages of biosilicate cements in pediatric dentistry are promising, this manuscript also discusses the limitations and challenges associated with their use. Some biosilicate cements may have different handling characteristics compared to traditional materials, necessitating adaptations in clinical techniques. In addition, long-term clinical data on the performance of these materials in pediatric patients are still limited, requiring further research to establish their efficacy and longevity. This manuscript explores the potential of biosilicate cements in pediatric dentistry.

Pengembangan Terapi Regeneratif pada Osteoartritis Sendi Temporomandibula : Telaah Pustaka

Temporomandibular joint osteoarthritis (TMJ OA) is a degenerative condition that affects the temporomandibular joint, causing pain, stiffness, and limited jaw movement. Conventional therapies such as medications, physical therapy, and surgery often only provide temporary solutions and cannot permanently restore joint function. Therefore, regenerative therapy has emerged as a promising approach to address TMJ OA by harnessing the body's natural healing potential. This literature review aims to provide a comprehensive overview of the development of regenerative therapies for TMJ OA, including therapeutic strategies, challenges, and future opportunities. Regenerative therapies for TMJ OA encompass various strategies, such as stem cell injections, biomaterial scaffolds, growth factors, gene therapy, and combination therapies. Although regenerative therapies have shown promising results in preclinical studies, several challenges remain, such as safety, efficacy, and translation into clinical applications. It can be concluded that regenerative therapy offers an innovative and potential approach to addressing TMJ OA by utilizing the body's natural healing capabilities, with the hope of restoring joint function and improving the quality of life for TMJ OA patients in the future.

Extracellular vesicles derived from human foreskin cells (hFS-Exo) accelerate cell migration and angiogenesis through MAPK pathway: an in vitro study.

Wound healing is one of the important processes in the body. Attempts to create new drugs are of interest due to the side effects of natural and chemical wound healing compounds. To overcome this obstacle, stem cells have been used as healing agents. However, both difficulties in collection and risks such as rejection and teratoma in the recipient body have limited the use of stem cells, directly. Since the potential content of the stem cells can be transferred to the recipient cells by vesicles, small extracellular vesicles have recently become prominent agents. The wound-healing effect of extracellular vesicles derived from foreskin cells was investigated in both keratinocyte and endothelial cells. Migration assay, RT-PCR, Col1a1 ELISA and Western Blot experiments were utilized to reveal healing effect of EVs and its possible molecular pathways. EV-treated groups exhibited more proliferative, invasive, and migrative characteristics. When comparing to the control group, new vessel formation was induced in EV groups. An increase in gene levels of growth factors related to wound healing and change in the mitogen-activated protein kinase (MAPK) signaling pathway proteins in EV-treated groups were determined. Possible molecular mechanisms underlying cell movements were associated with the MAPK pathway. It was found that human foreskin cell EVs (hFS-Exo) may have a potential to heal wounds in a short period of time by triggering the MAPK pathway. hFS-Exo could be a new promising wound healing agent in the future.

Advancements in Regenerative Hydrogels in Skin Wound Treatment: A Comprehensive Review.

This state-of-the-art review explores the emerging field of regenerative hydrogels and their profound impact on the treatment of skin wounds. Regenerative hydrogels, composed mainly of water-absorbing polymers, have garnered attention in wound healing, particularly for skin wounds. Their unique properties make them well suited for tissue regeneration. Notable benefits include excellent water retention, creating a crucially moist wound environment for optimal healing, and facilitating cell migration, and proliferation. Biocompatibility is a key feature, minimizing adverse reactions and promoting the natural healing process. Acting as a supportive scaffold for cell growth, hydrogels mimic the extracellular matrix, aiding the attachment and proliferation of cells like fibroblasts and keratinocytes. Engineered for controlled drug release, hydrogels enhance wound healing by promoting angiogenesis, reducing inflammation, and preventing infection. The demonstrated acceleration of the wound healing process, particularly beneficial for chronic or impaired healing wounds, adds to their appeal. Easy application and conformity to various wound shapes make hydrogels practical, including in irregular or challenging areas. Scar minimization through tissue regeneration is crucial, especially in cosmetic and functional regions. Hydrogels contribute to pain management by creating a protective barrier, reducing friction, and fostering a soothing environment. Some hydrogels, with inherent antimicrobial properties, aid in infection prevention, which is a crucial aspect of successful wound healing. Their flexibility and ability to conform to wound contours ensure optimal tissue contact, enhancing overall treatment effectiveness. In summary, regenerative hydrogels present a promising approach for improving skin wound healing outcomes across diverse clinical scenarios. This review provides a comprehensive analysis of the benefits, mechanisms, and challenges associated with the use of regenerative hydrogels in the treatment of skin wounds. In this review, the authors likely delve into the application of rational design principles to enhance the efficacy and performance of hydrogels in promoting wound healing. Through an exploration of various methodologies and approaches, this paper is poised to highlight how these principles have been instrumental in refining the design of hydrogels, potentially revolutionizing their therapeutic potential in addressing skin wounds. By synthesizing current knowledge and highlighting potential avenues for future research, this review aims to contribute to the advancement of regenerative medicine and ultimately improve clinical outcomes for patients with skin wounds.

Management of canine wounds using platelet-rich fibrin (PRF) biomaterial. A case series report.

The increasing interest in platelet-based therapies has underwritten the development of novel veterinary regenerative treatments. The haemoderivative platelet-rich fibrin (PRF) comprises abundant concentrations of platelets and leucocytes, above the physiologic baseline, which are considered essential elements for wound regeneration, stimulating local angiogenesis, cellular migration, proliferation and differentiation, considered essential for skin repair. This study aimed to describe the treatment of eight dogs with naturally occurring cutaneous wounds, where autologous PRF therapy was applied, using a protocol developed by our group. Eight dogs, aged between 7-month and 9-year old, from different breeds and sexes, were enrolled in this study. Four of these wounds were clinically infected. In three cases, two PRF treatments were performed during the first week of treatment, followed by single weekly treatments from the second week onwards, until exophytic granulation tissues were present. In each case, the treatment was finalized only when complete wound closure was achieved. Wounds did not receive topical antiseptics, antibiotics or topical drugs to promote wound healing during the treatment. PRF-grafting treatments were well tolerated in all treated wounds, inducing significant granulation tissue formation. PRF clots acted as a natural tissue filler, promoting epithelization and wound closure, without the requirement of topical antimicrobial/antiseptics application, or additional surgical debridement. Evident skin contraction was recorded in larger injuries and all the treatments resulted in vestigial aesthetic scars where hair growth was also observed. PRF-therapy obtained promising results, as an alternative wound treatment, revealing a biological regenerative action, prompting the natural skin healing process.

Topical gel preparation from Staphylococcus epidermidis isolate extract accelerated healing on incision wound model in rats

A wound is a disorder of skin integrity caused by physical trauma or disease. Wound healing is a natural restorative response to tissue injury. It is a complex dynamic physiological process involving several overlapping phases. Although wound management has been applied, however, some time it is associated withmajor drawbak including invasiveness, antibiotic resistance, and high costs. Natural medicines are being developed for wound management to resolve the drawback. Commensal Staphylococcus epidermidis was proven to play a role in natural wound healing process. This study aimed to investigate the wound healingactivity of a topical gel preparation containing S. epidermidis isolate extract on an incision wound model in rats. The methanol extract of S. epidermidis isolate was prepared by maceration and used as an active ingredient of the topical gel using NaCMC as a gelling agent. A physical stability test was carried out by assessingorganoleptic properties, pH value, homogeneity, dispersion, and viscosity of the gel preparation. The gel preparation was then topically applied once-daily for 11 d on incision wound model of male white rats (Rattus norvegicus). The wound healing was observed daily and calculated using Morton’s formula. Nosignificant change in the physical stability parameters of the gel preparation was observed during observation on day 1, 7, and 14 (p>0.05). A significant increase in wound healing after the application of the gel preparation compared to negative control was observed (p<0.05). In contrast, no significant difference inwound healing between the gel preparation and the positive control group was observed (p>0.05). In conclusion, the topical gel preparation from S. epidermidis isolate extract accelerates healing on incision wound models in rats.

A review of the current state of natural biomaterials in wound healing applications.

Skin, the largest biological organ, consists of three main parts: the epidermis, dermis, and subcutaneous tissue. Wounds are abnormal wounds in various forms, such as lacerations, burns, chronic wounds, diabetic wounds, acute wounds, and fractures. The wound healing process is dynamic, complex, and lengthy in four stages involving cells, macrophages, and growth factors. Wound dressing refers to a substance that covers the surface of a wound to prevent infection and secondary damage. Biomaterials applied in wound management have advanced significantly. Natural biomaterials are increasingly used due to their advantages including biomimicry of ECM, convenient accessibility, and involvement in native wound healing. However, there are still limitations such as low mechanical properties and expensive extraction methods. Therefore, their combination with synthetic biomaterials and/or adding bioactive agents has become an option for researchers in this field. In the present study, the stages of natural wound healing and the effect of biomaterials on its direction, type, and level will be investigated. Then, different types of polysaccharides and proteins were selected as desirable natural biomaterials, polymers as synthetic biomaterials with variable and suitable properties, and bioactive agents as effective additives. In the following, the structure of selected biomaterials, their extraction and production methods, their participation in wound healing, and quality control techniques of biomaterials-based wound dressings will be discussed.

탈모 및 두피특성에 따른 괄사요법 인지도와 만족도에 관한 연구

This study is a research study on awareness of meridian scraping therapy. Meridian scraper prevents many diseases and has the effect of keeping the body healthy and the face beautiful. Meridian scraper, which means ‘cure illness by scratching,’ is a natural healing method that cleanses away stubborn dirt from the body and unclogs clogged blood vessels, revitalizing energy, just by stimulating acupuncture points. However, despite this clinical research value, research on meridian scraper has been limited to simple body management or stress and has only confirmed that it is effective to some extent. In other words, the reality is that a sufficient theoretical summary of meridian scraper has not been achieved through prior research and a review of the scientific literature, and systematic clinical research based on the principles and theories derived from this summary is lacking. Considering the academic research value of meridian scraper, which has recently been in the spotlight again, it is judged that more in-depth research is needed, and it is hoped that further developmental research on meridian scraper will be conducted in the future based on research on the principles and efficacy of meridian scraping therapy.

Sustainable development of Georgian resorts: modern trends and challenges

In terms of development of tourism and resort resource potential, Georgia is an outstanding country, there has been interest in it since ancient times. Among the republics of the Soviet Union, Georgia was in one of the first places with diverse natural healing resources, and was especially distinguished by balneological and climatotherapy resources.The article discusses the development prospects of resort tourism in Georgia. The country has many health facilities, spaces and opportunities that can attract local and foreign visitors seeking treatment and health rehabilitation. Georgia has a great natural and cultural heritage, which allows us to restore old resorts and develop new resorts to ultimately create more value in the tourism sector.The paper shows that the country is divided into 11 climatic and 12 resort-recreational districts, where there are more than 102 resorts and up to 1802 resort places, the classification of which is based on the main recreational factor. Mountain climatic, balneological, seaside climatic, balneoclimatic, climatic-balneological resorts are analyzed. It is mentioned that the development of resorts is a very important direction in terms of realizing the tourist produqt of Georgia.

Differences between first- and second-generation autologous platelet concentrates.

Autologous platelet concentrates (APCs) applied alone or combined with other biomaterials are popular bioactive factors employed in regenerative medicine. The main biological rationale of using such products is to concentrate blood-derived growth factors and cells into the wound microenvironment to enhance the body's natural healing capacity. First-generation APC is represented by platelet-rich plasma (PRP). While different protocols have been documented for PRP preparation, they overall consist of two cycles of centrifugation and have important limitations related to the use of an anticoagulant first and an activator afterward, which may interfere with the natural healing process and the release of bioactive molecules. The second generation of platelet concentrates is represented by leukocyte and platelet-rich fibrin (L-PRF). L-PRF protocols involve a single centrifugation cycle and do not require the use of anticoagulants and activators, which makes the preparation more straight forward, less expensive, and eliminates potential risks associated with the use of activators. However, since no anticoagulant is employed, blood undergoes rapid clotting within the blood collection tube; hence, a timely management of L-PRF is crucial. This review provides an overview on the most documented protocols for APC preparations and critically discusses the main differences between first- and second-generation APCs in terms of cell content, protein release, and the formation of a 3D fibrin network. It appears evident that the inconsistency in reporting protocol parameters by most studies has contributed to conflicting conclusions regarding the efficacy of different APC formulations and has significantly limited the ability to interpret the results of individual clinical studies. In the future, the use of a standardized classification system, together with a detailed reporting on APC protocol parameters is warranted to make study outcomes comparable. This will also allow to clarify important aspects on the mechanism of action of APCs (like the role of leukocytes and centrifugation parameters) and to optimize the use of APCs in regenerative medicine.

Skin Numbness after Total Knee Arthroplasty: Complication or Side-Effect?

Peri-incisional numbness occurs frequently after Total Knee Arthroplasty (TKA), yet its impact on clinical outcomes remains controversial. With some studies reporting 100% incidence and patients often perceiving it as a minor inconvenience, its categorisation as a complication is controversial. This study investigates the prevalence and temporal changes of numbness post-TKA to refine the informed consent process and improve patient satisfaction. A convenience sample of patients who underwent primary cemented TKA was studied. Demographic data, scar length, tourniquet time, and WOMAC scores were collected. Patients were grouped based on time from surgery, and areas of numbness for light touch and pinprick sensations measured. The study included 49 patients with a mean age of 68.9 years. While all patients reported numbness, the area decreased for both pinprick and light touch sensations over time. No significant correlation was found between WOMAC scores and the area of numbness. Numbness post-TKA is common, and the affected area contracts over time, implying a natural healing process. The study's findings challenge the perception of numbness as a complication and emphasise the importance of informed consent in managing patient expectations. 1. Postoperative numbness around the incision site following TKA is a common occurrence with minimal clinical impact on patients. 2. It is important to inform patients that this numbness will improve, although some residual numbness may remain.

Fused Deposition Modeling 3D-Printed Scaffolds for Bone Tissue Engineering Applications: A Review.

The emergence of bone tissue engineering as a trend in regenerative medicine is forcing scientists to create highly functional materials and scaffold construction techniques. Bone tissue engineering uses 3D bio-printed scaffolds that allow and stimulate the attachment and proliferation of osteoinductive cells on their surfaces. Bone grafting is necessary to expedite the patient's condition because the natural healing process of bones is slow. Fused deposition modeling (FDM) is therefore suggested as a technique for the production process due to its simplicity, ability to create intricate components and movable forms, and low running costs. 3D-printed scaffolds can repair bone defects in vivo and in vitro. For 3D printing, variousmaterials including metals, polymers, and ceramics are often employed but polymeric biofilaments are promising candidates for replacing non-biodegradable materials due to their adaptabilityand environment friendliness. This review paper majorly focuses on the fused deposition modeling approach for the fabrication of 3D scaffolds. In addition, it also provides information on biofilaments used in FDM 3D printing, applications, and commercial aspects of scaffolds in bone tissue engineering.

Inhibitory Effect of Alternanthera Sessilis, Cucurbita Maxima and Aerva Lanata on Whewellite Urinary Crystals

Phosphate stones, such as struvite (magnesium ammonium phosphate hexahydrate), brushite (calcium hydrogen phosphate dihydrate), and oxalates like whewellite (calcium oxalate monohydrate) are different kinds of urinary stones. Such kidney stones can be treated with herbs for natural healing and side effects-free results. These urinary crystals are traditionally created in the lab using the gel growth process and a silica gel medium at a specified pH. The inhibitory effects can be analysed by using the extracts of herbal plants. In the present study, ethanol extracts of leaves of Alternanthera sessilis, seeds of Cucurbita maxima and flowers of Aerva lanata are investigated for their inhibitory activity against the whewellite urinary crystals. They are characterized using Fourier transform infrared spectrum and their crystalline nature is examined through powder X-ray diffraction. Asymmetric and symmetric stretching unit of C=O in oxalate appears at 1620 cm-1 and 1400, 1310 cm-1 respectively. The monoclinic crystal system with a space group of P21/n is confirmed from the powder X-ray diffraction studies. The results indicated that among the three ethanol extracts, leaves of Alternanthera sessilis, seeds of Cucurbita maxima and flowers of Aerva lanata- the flowers of Aerva lanata exhibited inhibition towards whewellite crystals. KEYWORDS Extract, flowers, herbs, oxalates, pH, seeds

Electrospun Biomimetic Periosteum Capable of Controlled Release of Multiple Agents for Programmed Promoting Bone Regeneration.

The effective repair of large bone defects remains a major challenge due to its limited self-healing capacity. Inspired by the structure and function of the natural periosteum, an electrospun biomimetic periosteum is constructed to programmatically promote bone regeneration using natural bone healing mechanisms. The biomimetic periosteum is composed of a bilayer with an asymmetric structure in which an aligned electrospun poly(ε-caprolactone)/gelatin/deferoxamine (PCL/GEL/DFO) layer mimics the outer fibrous layer of the periosteum, while a random coaxial electrospun PCL/GEL/aspirin (ASP) shell and PCL/silicon nanoparticles (SiNPs) core layer mimics the inner cambial layer. The bilayer controls the release of ASP, DFO, and SiNPs to precisely regulate the inflammatory, angiogenic, and osteogenic phases of bone repair. The random coaxial inner layer can effectively antioxidize, promoting cell recruitment, proliferation, differentiation, and mineralization, while the aligned outer layer can promote angiogenesis and prevent fibroblast infiltration. In particular, different stages of bone repair are modulated in a rat skull defect model to achieve faster and better bone regeneration. The proposed biomimetic periosteum is expected to be a promising candidate for bone defect healing.

Development of Biocompatible Digital Light Processing Resins for Additive Manufacturing Using Visible Light-Induced RAFT Polymerization.

Patients with bone diseases often experience increased bone fragility. When bone injuries exceed the body's natural healing capacity, they become significant obstacles. The global rise in the aging population and the escalating obesity pandemic are anticipated to lead to a notable increase in acute bone injuries in the coming years. Our research developed a novel DLP resin for 3D printing, utilizing poly(ethylene glycol diacrylate) (PEGDA) and various monomers through the PET-RAFT polymerization method. To enhance the performance of bone scaffolds, triply periodic minimal surfaces (TPMS) were incorporated into the printed structure, promoting porosity and pore interconnectivity without reducing the mechanical resistance of the printed piece. The gyroid TPMS structure was the one that showed the highest mechanical resistance (0.94 ± 0.117 and 1.66 ± 0.240 MPa) for both variants of resin composition. Additionally, bioactive particles were introduced to enhance the material's biocompatibility, showcasing the potential for incorporating active compounds for specific applications. The inclusion of bioceramic particles produces an increase of 13% in bioactivity signal for osteogenic differentiation (alkaline phosphatase essay) compared to that of control resins. Our findings highlight the substantial improvement in printing precision and resolution achieved by including the photoabsorber, Rose Bengal, in the synthesized resin. This enhancement allows for creating intricately detailed and accurately defined 3D-printed parts. Furthermore, the TPMS gyroid structure significantly enhances the material's mechanical resistance, while including bioactive compounds significantly boosts the polymeric resin's biocompatibility and bioactivity (osteogenic differentiation).

Prospects for integrating the Far East recreational potential into the medical rehabilitation system

In this article, we generalize the results a research study into natural healing resources in the Far East. The regions of the Russian Far East possess a significant and unique natural potential for comprehensive medical rehabilitation. The main therapeutic resources of the area, including its climate, mineral waters, and therapeutic muds, are characterized. Issues associated with the task of integrated use of natural and physical resources in effective spa treatment and comprehensive rehabilitation are discussed. The major action mechanisms of natural therapeutic factors widely used in spa treatment are outlined, and the possibilities of their integration with the system of medical rehabilitation are substantiated.

Effects of platelet‐rich fibrin on post‐extraction wound healing and wound pain: A meta‐analysis

AbstractWe conducted a meta‐analysis to assess the effect of platelet‐rich fibrin (PRF) on post‐extraction wound healing and pain, with a view to providing a reliable basis for the selection of treatment options in clinical practice. A computerised search of PubMed, EMBASE, Cochrane Library, China National Knowledge Infrastructure and Wanfang databases for studies on the effect of PRF on post‐extraction wound healing and pain compared with natural healing (control group) was performed from the time of creation of the respective databases to July 2023. Literature screening, data extraction and quality assessment were done independently by two authors. Meta‐analysis was performed using RevMan 5.4 software. Fourteen studies with a total of 508 patients were finally included. Meta‐analysis showed that the use of PRF relieved patients' wound pain (standardised mean differences [SMDs]: −1.78, 95% confidence intervals [CIs]: −2.61 to −0.94, p < 0.001), promoted soft tissue healing of extraction wounds (SMD: 1.09, 95% CIs: 0.26–1.91, p = 0.010) and also reduced the incidence of alveolar osteitis (AO) in patients after tooth extraction (2.42% vs. 10.14%, odds ratio: 0.27, 95% CIs: 0.11–0.65, p = 0.004). Current clinical evidence suggests that the use of PRFs can reduce patients' postoperative wound pain, promote soft tissue healing of extraction wounds and reduce the incidence of postoperative AO compared with natural healing. However, due to limitations in the number and quality of studies, large‐scale randomised controlled trials are still needed to validate the results of this study in the future.

Interpositional bone graft with cortical and cancellous calvarial bone for addressing the bone gap after reduction malarplasty: a case report

Asians typically exhibit prominent zygomas; therefore, several attempts have been made to reduce these structures to achieve a softer appearance. The intraoral approach is preferred because of its shorter surgical duration and lower invasiveness; however, it is associated with serious complications, such as nonunion. In revisional surgery, the intraoral approach poses limitations in accessing the upper part of the zygoma and the lateral orbital rim area due to its restricted operative field. Therefore, we developed an intraoral interpositional bone graft technique that enabled almost complete reconstruction. A 40-year-old woman presented with persistent depression in the left infraorbital and cheek regions after two revision operations after reduction malarplasty. Based on computed tomography (CT) scan findings, reconstruction using bone grafts was planned. Calvarial bone was harvested and divided into cortical and cancellous parts. The cortical bone was sculpted into an L-shape and inserted into the gap between the maxilla and the lower zygoma body. The hard-to-reach lateral orbital rim area was filled with cancellous bone without fixation. Follow-up CT scans showed that the cortical bone grafts were well-maintained and stabilized with titanium plates, while the cancellous bone had undergone significant resorption and was replaced by new bone, indicative of successful natural healing.

A novel and efficient murine model for investigating tendon-to-bone healing

BackgroundTendon-to-bone healing is a critical challenge in sports medicine, with its cellular and molecular mechanisms yet to be explored. An efficient murine model could significantly advance our understanding of this process. However, most existing murine animal models face limitations, including a propensity for bleeding, restricted operational space, and a steep learning curve. Thus, the need for a novel and efficient murine animal model to investigate the cellular and molecular mechanisms of tendon-to-bone healing is becoming increasingly evident.MethodsIn our study, forty-four 9-week-old male C57/BL6 mice underwent transection and reattachment of the Achilles tendon insertion to investigate tendon-to-bone healing. At 2 and 4 weeks postoperatively, mice were killed for histological, Micro-CT, biomechanical, and real-time polymerase chain reaction tests.ResultsHistological staining revealed that the original tissue structure was disrupted and replaced by a fibrovascular scar. Although glycosaminoglycan deposition was present in the cartilage area, the native structure had been destroyed. Biomechanical tests showed that the failure force constituted approximately 44.2% and 77.5% of that in intact tissues, and the ultimate tensile strength increased from 2 to 4 weeks postoperatively. Micro-CT imaging demonstrated a gradual healing process in the bone tunnel from 2 to 4 weeks postoperatively. The expression levels of ACAN, SOX9, Collagen I, and MMPs were detected, with all genes being overexpressed compared to the control group and maintaining high levels at 2 and 4 weeks postoperatively.ConclusionsOur results demonstrate that the healing process in our model is aligned with the natural healing process, suggesting the potential for creating a new, efficient, and reproducible mouse animal model to investigate the cellular and molecular mechanisms of tendon-to-bone healing.Graphical abstract

3D Niche-Inspired Scaffolds as a Stem Cell Delivery System for the Regeneration of the Osteochondral Interface.

The regeneration of the osteochondral unit represents a challenge due to the distinct cartilage and bone phases. Current strategies focus on the development of multiphasic scaffolds that recapitulate features of this complex unit and promote the differentiation of implanted bone-marrow derived stem cells (BMSCs). In doing so, challenges remain from the loss of stemness during in vitro expansion of the cells and the low control over stem cell activity at the interface with scaffolds in vitro and in vivo. Here, this work scaffolds inspired by the bone marrow niche that can recapitulate the natural healing process after injury. The construct comprises an internal depot of quiescent BMSCs, mimicking the bone marrow cavity, and an electrospun (ESP) capsule that "activates" the cells to migrate into an outer "differentiation-inducing" 3D printed unit functionalized with TGF-β and BMP-2 peptides. In vitro, niche-inspired scaffolds retained a depot of nonproliferative cells capable of migrating and proliferating through the ESP capsule. Invasion of the 3D printed cavity results in location-specific cell differentiation, mineralization, secretion of alkaline phosphatase (ALP) and glycosaminoglycans (GAGs), and genetic upregulation of collagen II and collagen I. In vivo, niche-inspired scaffolds are biocompatible, promoted tissue formation in rat subcutaneous models, and regeneration of the osteochondral unit in rabbit models.