Primed IFN-γ-Umbilical Cord Stem Cells Ameliorate Temporomandibular Joint Osteoarthritis.

Temporomandibular joint osteoarthritis (TMJOA) is a degenerative disorder affecting the temporomandibular joint (TMJ), marked by persistent inflammation and structural damage to the joint. Only symptomatic treatment is available for managing TMJOA. Human umbilical cord mesenchymal stem cells (hUC-MSCs) show potential for treating TMJOA via their immune-modulating actions in the disease area. In addition, stimulation of inflammatory cytokines such as interferon-gamma in hUC-MSCs improves the therapeutic activity of naïve stem cells. Emerging evidence indicates that macrophages play significant roles in regulating joint inflammation through diverse secreted mediators in the pathogenesis of TMJOA. This study was conducted to evaluate the effects of inflammatory cytokine-stimulated hUC-MSCs in repairing TMJOA-induced cartilage lesions and the role of macrophages in the disease. Our in vitro data showed that stimulated hUC-MSCs induce M2 polarization of macrophages and enhance the expression of anti-inflammatory molecules. These effects were subsequently validated in vivo. In a rat model of TMJOA, stimulated hUC-MSCs ameliorated inflammation and increased M2 macrophages ratio. Our results indicate that hUC-MSCs stimulated by inflammatory cytokines modulate the activation of M2 macrophages, thereby shifting the local osteoarthritis microenvironment toward a prochondrogenic state and facilitating cartilage repair in inflammatory conditions. Stimulating hUC-MSCs with inflammatory cytokines could potentially offer an effective therapeutic approach for TMJOA, with macrophages playing a pivotal role in immune modulation.

Efficacy of IFN-γ-Primed Umbilical Cord-Derived Mesenchymal Stem Cells on Temporomandibular Joint Osteoarthritis.

BACKGROUND: Temporomandibular joint osteoarthritis (TMJOA) is a degenerative disease affecting the cartilage and subchondral bone, leading to temporomandibular joint pain and dysfunction. The complex nature of TMJOA warrants effective alternative treatments, and mesenchymal stem cells (MSCs) have shown promise in regenerative therapies. The aim of this study is twofold: firstly, to ascertain the optimal interferon-gamma (IFN-γ)-primed MSC cell line for TMJOA treatment, and secondly, to comprehensively evaluate the therapeutic efficacy of IFN-γ-primed mesenchymal stem cells derived from the human umbilical cord matrix in a rat model of TMJOA. METHODS: We analyzed changes in the expression of several key genes associated with OA protection in MSC-secreted compounds. Following this, we performed co-culture experiments using a transwell system to predict gene expression changes in primed MSCs in the TMJOA environment. Subsequently, we investigated the efficacy of the selected IFN-γ-primed human umbilical cord matrix-derived MSCs (hUCM-MSCs) for TMJOA treatment in a rat model. RESULTS: IFN-γ-primed MSCs exhibited enhanced expression of IDO, TSG-6, and FGF-2. Moreover, co-culturing with rat OA chondrocytes induced a decrease in pro-inflammatory and extracellular matrix degradation factors. In the rat TMJOA model, IFN-γ-primed MSCs with elevated IDO1, TSG-6, and FGF2 expression exhibited robust anti-inflammatory and therapeutic capacities, promoting the improvement of the inflammatory environment and cartilage regeneration. CONCLUSION: These findings underscore the importance of prioritizing the mitigation of the inflammatory milieu in TMJOA treatment and highlight IFN-γ-primed MSCs secreting these three factors as a promising, comprehensive therapeutic strategy.

Efficacy of pure beta tricalcium phosphate graft in dentoalveolar surgery: a retrospective evaluation based on serial radiographic images.

BACKGROUND: The use of beta-tricalcium phosphate (beta-TCP) in dental surgery is limited owing to its rapid absorption compared to mixed formulations of hydroxyapatite. However, newly developed pure beta-TCP crystals have demonstrated slow absorption; hence, they last longer within the defect and act as a scaffold until new bone formation. The oral environment is unique and can prove unfavorable for bone grafts due to the high infection rate in the oral cavity and the fragile condition of the oral mucosa. The aim of this study was to evaluate the feasibility of using pure beta-TCP bone grafts in various dental treatments. METHODS: Panoramic X-ray images of 25 patients who underwent bone grafting during dental surgery were analyzed. A specially treated pure beta-TCP crystal, Neo Bone® (Neo Bone®, SN Biologics Co., Ltd, Seoul, Korea), was used in this study. The bone density at the graft site was compared with that of the surrounding bone using the ImageJ software (Wayne Rasband, NIH USA). RESULTS: Six months after surgery, the bone graft density was similar to that of the surrounding bone in 20 patients and increased in 5 patients. No adverse effects, such as infection, dehiscence, or graft failure, were observed. CONCLUSION: The newly developed pure beta-TCP crystal was slowly absorbed and served as support until new bone formation at the defect site, thus demonstrating its potential for use in various oral conditions requiring bone grafting.

Effective Technical Protocol for Producing a Mono-Iodoacetate-Induced Temporomandibular Joint Osteoarthritis in a Rat Model.

An animal model of osteoarthritis (OA) induced by monosodium iodoacetate (MIA) can be effectively adjusted based on the concentration of MIA to control the onset, progression, and severity of OA as required. The rat temporomandibular joint osteoarthritis (TMJOA) model using MIA is a useful tool for studying the effectiveness of disease-modifying OA drugs in TMJOA research. However, the intricate and complex anatomy of the rat TMJ often poses challenges in achieving consistent TMJOA induction during experiments. In the previous article, a reference point was established by drawing parallel lines based on the line connecting the external ear and the zygomatic arch. However, this is not suitable for the anatomical characteristics of the rat. We used the zygomatic arch as a reference, which is a technical protocol that considers it. In our protocol, we designated a point ∼1 mm away from the point where the zygomatic arch bends toward the ear as the injection site. To ensure precise injection of MIA and increase the likelihood of inducing OA, it is recommended to insert the needle at a 45° angle so that the needle tip contacts the joint projection. To confirm TMJOA induction, we identified changes in the condyle using in vivo microcomputed tomography (CT) in a rat model of MIA-induced OA and measured the degree of pain-related inflammation using head withdrawal threshold (HWT) measurements. Micro-CT scanning revealed typical OA-like lesions, including degenerative changes and subchondral bone remodeling induced by MIA in the TMJ. Pain, a major clinical feature of OA, showed an appropriate response corresponding to the structural changes shown in micro-CT scanning. In addition, the MIA concentration suitable for long-term observation of lesions was determined through ex vivo micro-CT imaging and HWT measurements. The 8 mg concentration exhibited a significant difference compared with others, confirming the sustained presence of lesions, particularly through changes in subchondral bone over an extended period. Consequently, we have successfully established a reliable rat TMJOA induction model and identified the MIA concentration suitable for long-term observation of subchondral bone research, which will greatly contribute to the study of TMJOA-an incurable disease lacking specific treatment options. The Clinical Trial Registration number is 2021-12-208.

Biocompatibility evaluation of peo-treated magnesium alloy implants placed in rabbit femur condyle notches and paravertebral muscles.

BACKGROUND: Magnesium alloys have been receiving much attention for use in biodegradable metal implants because of their excellent mechanical properties and biocompatibility. However, their rapid breakdown and low bioactivity can cause the implant to lose mechanical integrity before the bone is completely healed. Moreover, hydrogen gas released during degradation can significantly delay the tissue regeneration process. To solve the instability of magnesium alloys, Zn and Ca can be added to improve the mechanical properties and biocompatibility. One other way to improve the mechanical properties of Mg is plasma electrolytic oxidation (PEO), which provides a dense, thick ceramic-like coating on the Mg surface. In this study, high-purity Mg was selected as the control, and Mg-1wt%Zn-0.1wt%Ca alloy and PEO-treated Mg-1wt%Zn-0.1wt%Ca alloy were selected as the test materials; the results of radiographic and histological analyses of their biocompatibility are reported herein. MATERIALS AND METHOD: Nineteen New Zealand white rabbits were used in the study. Rod-bars (Ø2.7 × 13.6 mm) were placed on both paravertebral muscles, and cannulated screws (Ø2.7x10mm) were placed on both femur condyle notches. Each animal was implanted in all four sites. X-rays were taken at 0, 2, 4, 8, and 12 weeks, micro-CT, and live-CT were taken at 4, 8, and 12 weeks. At weeks 4, 8, and 12, individuals representing each group were selected and sacrificed to prepare specimens for histopathological examination. RESULT: The results confirm that in vivo, Mg-1wt%Zn-0.1wt%Ca alloy had higher corrosion resistance than high-purity Mg and safely degraded over time without causing possible side effects (foreign body or inflammatory reactions, etc.). In addition, PEO treatment of Mg-1wt%Zn-0.1wt%Ca alloy had a positive effect on fracture recovery by increasing the bonding area with bone. CONCLUSION: Our results suggest that PEO treatment of Mg-1wt%Zn-0.1wt%Ca alloy can be a promising biomaterials in the field of various clinical situations such as orthopedic and maxillofacial surgerys.

An additional lysis procedure during arthrocentesis of the temporomandibular joint.

BACKGROUND: Arthrocentesis of the temporomandibular joint (TMJ) is an easy, highly efficient, minimally invasive procedure for treating temporomandibular joint disorders (TMDs). However, in some cases of mouth opening limitation (MOL), routine arthrocentesis is ineffective due to severe fibrotic adhesion in the superior joint space of the TMJ. In this condition, mechanical lysis of the adhesions might be needed to resolve the MOL, as well as other symptoms, such as chronic pain. Currently, this can be achieved by arthroscopic surgery or open TMJ surgery. The objective of this study was to introduce and evaluate our trial of the adhesion lysis procedure during arthrocentesis of the TMJ using normal 18-gauge needles. RESULTS: In this study, 40 patients with MOL due to disc derangement underwent conventional arthrocentesis at first and then physical detachment was conducted using the same needle. The change in maximum mouth opening (MMO) and the pain at the TMJ were recorded before, during, and after treatment according to our protocol. The mean increase in MMO after conventional arthrocentesis was 6.6 ± 4.2mm. The mean increase in MMO after the detachment procedure with the same needle was 4.2 ± 2.0 mm. The MMO in ten patients was significantly increased after the detachment procedure than after arthrocentesis alone. In all cases, the pain intensity in the TMJ significantly decreased over time, whereas the MMO increased over time. No adverse effect was observed in all joints during our observation periods. CONCLUSION: We confirmed that our simple lysis procedure with the same needle of the arthrocentesis of the TMJ could not only improve the MMO more than after a conventional arthrocentesis but also resolve severe adhesion of the joint space that was ineffective by conventional arthrocentesis. Although this additional lysis procedure is simple, it might reduce the number of cases of more invasive procedures such as arthroscopic surgery or open TMJ surgery.

Recent Trends in Orthognathic Surgery in Asia.

Anatomy and standards of beauty are different between Asians and Westerners. Unlike Westerners, Asians have a wide and prominent jaw shape but prefer a slim and soft face shape. To achieve this goal, maxillary setback and/or posterior impaction surgeries are popular among upper jaw surgery, and various adjuvant surgeries are performed simultaneously on the mandible to obtain the so-called oval shape or V-line face. In addition, according to the development of virtual surgery software and orthodontic treatment techniques, the surgery-first approach is now accepted as a reliable option for orthognathic surgery if it is indicated.

Efficient Design of a Clear Aligner Attachment to Induce Bodily Tooth Movement in Orthodontic Treatment Using Finite Element Analysis.

Clear aligner technology has become the preferred choice of orthodontic treatment for malocclusions for most adult patients due to their esthetic appeal and comfortability. However, limitations exist for aligner technology, such as corrections involving complex force systems. Composite attachments on the tooth surface are intended to enable active control of tooth movements. However, unintended tooth movements still occur. In this study, we present an effective attachment design of an attachment that can efficiently induce tooth movement by comparing and analyzing the movement and rotation of teeth between a general attachment and an overhanging attachment. The 3D finite element modes were constructed from CBCT data and used to analyze the distal displacement of the central incisor using 0.5- and 0.75-mm-thick aligners without an attachment, and with general and overhanging attachments. The results show that the aligner with the overhanging attachment can effectively reduce crown tipping and prevent axial rotation for an intended distal displacement of the central incisor. In all models, an aligner with or without attachments was not capable of preventing the lingual inclination of the tooth.

Effect of Human Umbilical Cord Matrix-Derived Mesenchymal Stem Cells on Bisphosphonate-Related Osteonecrosis of the Jaw.

BACKGROUND: Bisphosphonate-related osteonecrosis of the jaw (BRONJ) is a severe sequela caused by bisphosphonates (BPs), which are widely used to treat osteoporosis or other malignancies. However, the mechanism underlying BRONJ remains unclear. Recently, human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) have been studied for treatment of diverse diseases and injuries. This study aimed to investigate the therapeutic effects of hUC-MSCs in BRONJ. METHODS: The therapeutic effects of hUC-MSCs were examined in rat bone marrow (rBM)-derived cells using cell viability, colony-forming, and real-time PCR assays and FACS for analyzing essential proinflammatory and bone regeneration markers in vitro. To demonstrate the in vivo therapeutic and adverse effects of transfused hUC-MSCs, micro-CT, H&E staining, IHC (Angiogenesis marker gene expression) staining, and parathyroid hormone (PTH)/calcium assay were conducted in a BRONJ-induced animal model. RESULTS: BP-induced cytotoxicity and inflammation in rBM-derived cells decreased, after co-culture with hUC-MSCs. The expression levels of bone regeneration markers (RUNX2, OSX, and BMP-2) significantly increased in BP-treated rBM-derived cells, after co-culture with hUC-MSCs. The BP-induced abnormal shift in RANKL/OPG expression ratio in rBM-derived cells was normalized by hUC-MSCs. Consistent with these in vitro results, transfused hUC-MSCs markedly decreased BRONJ and significantly healed injured mucosa in the BRONJ-induced animal model. The animals exhibited serious destruction of the kidney structure and increases in serum PTH and calcium levels, which were significantly normalized by hUC-MSC transfusion. CONCLUSION: hUC-MSCs exerted therapeutic effects on BRONJ in vitro and in vivo through their anti-cytotoxicity, anti-inflammatory activity and ability to recover bone regeneration.

Onlay-graft of 3D printed Kagome-structure PCL scaffold incorporated with rhBMP-2 based on hyaluronic acid hydrogel.

The onlay-graft, one of the most difficult graft conditions, is used for diverse clinical conditions, including plastic and dental surgery. The graft should withstand continuous pressure from overlying tissues and have excellent bone formation capability in a limited bone contact situation. We recently developed a 3D printed Kagome-structured polycaprolactone (PCL) scaffold that has a stronger mechanical property. This study evaluated the clinical feasibility of this scaffold for onlay-graft use. The value of the scaffold containing recombinant human bone morphogenetic protein-2 in a hyaluronate-based hydrogel (rhBMP-2/HA) to enhance bone regeneration was also assessed. 3D-printed Kagome-PCL scaffolds alone (n= 12, group I) or loaded with rhBMP-2/HA (n= 12, group II) were grafted using a rat calvarial onlay-graft model. Following sacrifice at 2, 4, and 8 weeks, all 3D-printed Kagome-PCL scaffolds were accurately positioned and firmly integrated to the recipient bone. Micro-computed tomography and histology analyses revealed a constant height of the scaffolds over time in all animals. New bone grew into the scaffolds in both groups, but with greater volume in group II. These results suggest the promising clinical feasibility of the 3D-printed Kagome-PCL scaffold for onlay-graft use and it could substitute the conventional onlay-graft in the plastic and dental reconstructive surgery in the near future.

Association of maxillary dental developmental abnormality with precocious puberty: a case-control study.

BACKGROUND: Dental studies of precocious puberty have focused on examination of jaw and dentition growth. The aim of the study was to analyze the relationship between precocious puberty and maxillary dental developmental abnormalities (DDAs). METHODS: This retrospective study was conducted on the Korean patients in whom dental panoramic and hand-wrist radiographs had been taken before they were 15 years of age. The maxillary DDAs were assessed as mesiodens, congenital missing teeth, peg-shape lateral incisors, or impacted teeth. The chronological ages of the control group members were within the normal range of the hand-wrist bone age. Others with a peak luteinizing hormone of ≥ 5 and < 5 IU/L were allocated to central precocious puberty (CPP) and peripheral precocious puberty (PPP), respectively. RESULTS: Of the enrolled 270 patients, 195, 52, and 23 were allocated to the control, CPP, and PPP groups, respectively. The maxillary DDAs were significantly more prevalent in the CPP group than in the other groups. Among those with maxillary DDA, the mesiodens predominated. Age- and sex-adjusted multivariate analysis revealed maxillary DDA (odds ratio, 3.36; 95% CI, 1.60-7.05) and especially mesiodens (odds ratio, 5.52; CI, 2.29-13.28) to be significantly associated with CPP. CONCLUSIONS: Maxillary DDAs were significantly more prevalent in the CPP group than in the PPP or control groups. Among the many types of maxillary DDAs, mesiodens was significantly associated with CPP and may be considered a predictor of the development of CPP.

Temporomandibular joint disc plication with MITEK mini anchors: surgical outcome of 65 consecutive joint cases using a minimally invasive approach.

BACKGROUND: The purpose of this study is to introduce our modified disc plication technique using MITEK mini anchors and to evaluate the clinical outcome for patients with internal derangement (ID) of the temporomandibular joint (TMJ). PATIENTS AND METHODS: We evaluated 65 joints in 46 patients, comprised 32 women and 14 men, who first visited the Asan Medical Center from December 2012 to December 2016. The age of the patients ranged from 14 to 79 years, with a mean age of 36.6 years. The patients presented with joint problems including pain, joint noise, and mouth opening limitation (MOL). Patients who met our inclusion criteria underwent unilateral or bilateral disc repositioning surgery with our minimally invasive disc plication technique using MITEK mini anchors and No. 2-0 Ethibond® braided polyester sutures. The variables taken into account in this study were the range of maximum mouth opening (MMO), painful symptoms (evaluated with the visual analog scale, VAS), and the type of noise (click, popping, crepitus) in the TMJ. RESULTS: Preoperative examination revealed painful symptoms in 50.7% (n = 35) of the operated joints (n = 69) and the presence of clicks in 56.5% (n = 39). Postoperative examination revealed that 4.3% (n = 3) of the operated joints had painful symptoms with lower intensity than that in the preoperative condition. Additionally, 17.4% (n = 12) had residual noise in the TMJ, among which two were clicking and the other 10 had mild crepitus. The intensity of the postoperative residual noise was significantly decreased in all cases compared to that in the preoperative condition. Among patients with MOL below 38 mm (n = 18), the mean MMO was 31.4 mm preoperatively and 44.2 mm at 6 months postoperatively, with a mean increase of 13.8 mm. A barely visible scar at the operation site was noted during the postoperative observation period, with no significant complications such as facial palsy or permanent occlusal disharmony. CONCLUSION: Subjective symptoms in all patients improved following the surgery. TMJ disc plication using MITEK mini anchors with our minimally invasive approach may be a feasible and effective surgical option for treating TMJ ID patients who are not responsive to conservative treatment.

Anti-Inflammatory Effect of Adipose-Derived Stromal Vascular Fraction on Osteoarthritic Temporomandibular Joint Synoviocytes.

BACKGROUND: Osteoarthritis (OA) in the temporomandibular joint (TMJ) in the TMJ (TMJ-OA) is difficult to treat, and new alternative treatments are needed. Recently, adipose-derived stem cells (ASCs) have been introduced as a promising cell source because of their anti-inflammatory effects. However, the cost and availability of these cells limited broader applications of stem cell therapy. Thus, Thus, stromal vascular fraction (SVF) containing sufficient amount of ASCs at low cost can be an alternative. In this study, we aimed to demonstrate the use of uncultured, optimally isolated SVF for the treatment of TMJ-OA. METHODS: First, we optimized the method of isolation to harvest high-quality SVFs with a large yield of ASCs. Then, we analyzed the quantity of ASCs in the SVF and performed characterization of stem cell homology. Subsequently, to evaluate the anti-inflammatory effect of high-quality SVF, an in vitro study was performed to assess the expression patterns of inflammatory cytokines including prostaglandin E2 (PGE2), IL-6, and CXCL8/IL-8, COX2, TNF, IFN, CCL2/MCP-1 and CCL5/RANTES in co-culture with synoviocytes derived from the synovial fluid in the TMJ-OA patients. RESULTS: The SVF containing approximately 32% ASCs was isolated via the our optimized isolation method. The SVF significantly down-regulated certain inflammatory cytokines such as PGE2, CXCL8/IL-8 in TMJ-OA tissue-derived synoviocytes. CONCLUSION: Although further study is needed, our study suggests that transplantation of adipose tissue-derived SVF cells might be a feasible and a novel therapeutic option for TMJ-OA in the future.

Histological Review of Demineralized Dentin Matrix as a Carrier of rhBMP-2.

In 2007, recombinant human bone morphogenetic protein-2 (rhBMP-2) was approved for use in humans at a concentration of 1.5 mg/mL with absorbable collagen sponges as an alternative to autogenous bone grafts for alveolar ridge augmentation, defects associated with extraction sockets, and sinus augmentation. However, the use of supraphysiological doses and the insufficient retention of rhBMP-2, when delivered through collagen sponge, result in dose-dependent side effects related to off-label use. Demineralized dentin matrix (DDM), an osteoinducing bone substrate, has been used as an rhBMP-2 carrier since 1998. In addition, DDM has both microparticle and nanoparticle structures, which do not undergo remodeling, unlike bone. In vitro, DDM is a suitable carrier for BMP-2, with the continued release over 30 days at concentrations sufficient to stimulate osteogenic differentiation. In this review, we discuss the histological outcomes of DDM loaded with rhBMP-2 to highlight the biological functions of exogenous rhBMP-2 associated with the DDM carrier in clinical applications in implant dentistry. Impact Statement Demineralized dentin matrix (DDM) has been used as an recombinant human bone morphogenetic protein (rhBMP-2) carrier and osteo-inducing bone substrate to facilitate continued release and stimulate osteogenic differentiation. In this review, we discuss the histological outcomes of DDM loaded with rhBMP-2 in order to highlight the biological functions of exogenous rhBMP-2 associated with the DDM carrier in clinical applications in implant dentistry.

Comparison of Squamous Cell Carcinoma of the Tongue between Young and Old Patients.

BACKGROUND: The worldwide incidence of squamous cell carcinoma of the tongue (SCCOT) in young patients has been increasing. We investigated clinicopathologic features of this unique population and compared them with those of SCCOT in the elderly to delineate its pathogenesis. METHODS: We compared clinicopathological parameters between patients under and over 45 years old. Immunohistochemical assays of estrogen receptor, progesterone receptor, androgen receptor, p53, p16, mdm2, cyclin D1, and glutathione S-transferase P1 were also compared between them. RESULTS: Among 189 cases, 51 patients (27.0%) were under 45 years of age. A higher proportion of women was seen in the young group, but was not statistically significant. Smoking and drinking behaviors between age groups were similar. Histopathological and immunohistochemical analysis showed no significant difference by age and sex other than higher histologic grades observed in young patients. CONCLUSIONS: SCCOT in young adults has similar clinicopathological features to that in the elderly, suggesting that both progress via similar pathogenetic pathways.

Corrigendum: Dental alloplastic bone substitutes currently available in Korea.

[This corrects the article on p. 51 in vol. 45, PMID: 31106133.].

Therapeutic effect of mesenchymal stem cells derived from human umbilical cord in rabbit temporomandibular joint model of osteoarthritis.

Osteoarthritis (OA) is a degenerative condition of the temporomandibular joint (TMJ) characterised by chronic inflammation and damage to joint structures. Because of the complexity of TMJ-OA, only symptomatic treatments are currently available. Recent reports have shown that many of stem cells can exert anti-inflammatory and tissue-regenerating effects. In this study, we investigated the potential cartilage-regenerating and anti-inflammatory effects of human umbilical cord matrix-mesenchymal stem cells (hUCM-MSCs) for the treatment of TMJ-OA. hUCM-MSC lines, isolated from different donors, which showed different activities in vitro. Using a selected cell line, we used different concentrations of hUCM-MSCs to assess therapeutic effects in a rabbit model of monosodium iodoacetate-induced TMJ-OA. Compared with the untreated control group, the potential regenerative result and anti-inflammatory effects of hUCM-MSCs were evident at all the tested concentrations in rabbits with induced TMJ-OA. The median dose of hUCM-MSCs showed the prominent cartilage protective effect and further cartilage regeneration potential. This effect occurred via upregulated expression of growth factors, extracellular matrix markers, and anti-inflammatory cytokines, and reduced expression of pro-inflammatory cytokines. The anti-inflammatory effect of hUCM-MSCs was comparable to that of dexamethasone (DEX). However, only hUCM-MSCs showed potential chondrogenesis effects in this study. In conclusion, our results indicate that hUCM-MSCs may be an effective treatment option for the treatment of TMJ-OA.

Postulated release profile of recombinant human bone morphogenetic protein-2 (rhBMP-2) from demineralized dentin matrix.

Demineralized dentin matrix (DDM) has been used as a recombinant human bone morphogenetic protein-2 (rhBMP-2) carrier in many clinical trials. To optimize the clinical safety and efficacy of rhBMP-2 with DDM, efforts have been made to improve the delivery of rhBMP-2 by 1) lowering the administered dose, 2) localizing the protein, and 3) prolonging its retention time at the action site as well as the bone forming capacity of the carrier itself. The release profile of rhBMP-2 that is associated with endogenous BMP in dentin has been postulated according to the type of incorporation, which is attributed to the loosened interfibrillar space and nanoporous dentinal tubule pores. Physically adsorbed and modified, physically entrapped rhBMP-2 is sequentially released from the DDM surface during the early stage of implantation. As DDM degradation progresses, the loosened interfibrillar space and enlarged dentinal tubules release the entrapped rhBMP-2. Finally, the endogenous BMP in dentin is released with osteoclastic dentin resorption. According to the postulated release profile, DDM can therefore be used in a controlled manner as a sequential delivery scaffold for rhBMP-2, thus sustaining the rhBMP-2 concentration for a prolonged period due to localization. In addition, we attempted to determine how to lower the rhBMP-2 concentration to 0.2 mg/mL, which is lower than the approved 1.5 mg/mL.

Use of uniformly sized muscle fiber fragments for restoration of muscle tissue function.

Treatment of extensive muscle loss due to traumatic injury, congenital defects, or tumor ablations is clinically challenging. The current treatment standard is grafting of autologous muscle flaps; however, significant donor site morbidity and graft tissue availability remain a problem. Alternatively, muscle fiber therapy has been attempted to treat muscle injury by transplanting single fibers into the defect site. However, irregularly organized long fibers resulted in low survivability due to delay in vascular and neural integration, thus limiting the therapeutic efficacy. Therefore, no effective method is available to permanently restore extensive muscle injuries. To address the current limitations, we developed a novel method that produces uniformly sized native muscle fiber fragments (MFFs) for muscle transplantation. We hypothesized that fragmentation of muscle fibers into small and uniformly sized fragments would allow for rapid reassembly and efficient engraftment within the defect site, resulting in accelerated recovery of muscle function. Our results demonstrate that the processed MFFs have a dimension of approximately 100 µm and contain living muscle cells on extracellular matrices. In preclinical animal studies using volumetric defect and urinary incontinence models, histological and functional analyses confirmed that the transplanted MFFs into the injury sites were able to effectively integrate with host muscle tissue, vascular, and neural systems, which resulted in significant improvement of muscle function and mass. These results indicate that the MFF technology platform is a promising therapeutic option for the restoration of muscle function and can be applied to various muscle defect and injury cases.