Fibulin-2: A potential regulator of immune dysfunction after bone trauma.

OBJECTIVES: To reveal the relationship between the fibulin-2 protein and immune dysfunction after bone trauma. METHODS: Individuals who were admitted to the study were divided into a bone trauma group, a recovered from bone trauma group and a volunteer without bone trauma group based on the reason for admission. Fibulin-2 levels in the three groups were compared. Fibulin-2-knockout (fibulin-2-/- ) mice and wild-type (WT) mice were used to detect susceptibility to infection. Hematoxylin and eosin (HE) staining and immunohistochemical staining were employed to observe pathological changes in each organ from fibulin-2-/- mice and WT mice. RESULTS: In total, 132 patients were enrolled in this study. The fibulin-2 level in the bone trauma group was lower than that in the recovered bone trauma group (3.39 ± 1.41 vs. 4.30 ± 1.38 ng/mL, t = 2.948, p < .05) and also lower than that in the volunteers without bone trauma group (3.39 ± 1.41 vs. 4.73 ± 1.67 ng/mL, t = 4.135, p < .05). Fibulin-2-/- mice are more prone to infection. Compared with those in WT mice, spleen function and thymus function in fibulin-2-/- mice were impaired. Immunohistochemical staining revealed that compared with those in WT mice, significantly fewer CD4+ T cells, CD8+ T cells, and CD19+ B cells were noted in the spleen and thymus of fibulin-2-/- mice. CONCLUSIONS: The plasma fibulin-2 level was lower in patients with bone trauma. Decreased fibulin-2 is associated with immune dysfunction after bone trauma.

[How I treat... a fracture of the coronoid apophysis, choice between conservative attitude and surgical treatment]. / Comment je traite...une fracture de l'apophyse coronoïde, entre attitude conservatrice et traitement chirurgical.

Fractures of the coronoid process are the rarest mandibular fractures and are mostly associated with other maxillofacial fractures. They are most often encountered in trauma. The CT-scanner is the gold standard for locating and characterizing this lesion. Although the diagnosis is made radiologically, clinical examination may reveal various symptoms specific to this fracture, which may appear frustrated when other facial fractures are associated. In most cases, conservative treatment by intermaxillary fixation is preferred. However, in specific cases, surgical intervention such as coronoidectomy or open reduction with osteosynthesis is indicated. The type of fracture, its location, the delay before its management, the clinic and the presence of associated fractures guide the therapeutic attitude. Surgical management must be followed by early and intensive physiotherapy to avoid zygomatico-coronoid ankylosis, the main complication of this fracture.

Les fractures de l'apophyse coronoïde sont les fractures mandibulaires les plus rares et majoritairement associées à d'autres fractures maxillo-faciales. Elles se rencontrent le plus souvent lors de traumatisme. Le CT-scanner est le gold standard pour localiser et caractériser cette lésion. Bien que le diagnostic soit radiologique, l'examen clinique peut révéler différents symptômes propres à cette fracture et qui peuvent paraître frustres lorsque d'autres fractures du massif facial y sont associées. Dans la majorité des cas, le traitement conservateur par fixation intermaxillaire est privilégié. Mais dans des indications précises, une intervention chirurgicale, comme une coronoïdectomie ou une réduction ouverte avec ostéosynthèse, est indiquée. Le type de fracture, sa localisation, le délai avant sa prise en charge, la clinique et la présence de fractures associées guident l'attitude thérapeutique. Une prise en charge chirurgicale doit être suivie de physiothérapie précoce et intensive pour éviter l'ankylose zygomatico-coronoïde, principale complication de cette fracture.

Microtomographic, histomorphometric, and molecular features show a normal alveolar bone healing process in iNOS-deficient mice along a compensatory upregulation of eNOS and nNOS isoforms.

METHODOLOGY: Inducible nitric oxide synthase (iNOS) is one of the enzymes responsible for the synthesis of nitric oxide (NO), which is an important signaling molecule with effects on blood vessels, leukocytes, and bone cells. However, the role of iNOS in alveolar bone healing remains unclear. This study investigated the role of iNOS in alveolar bone healing after tooth extraction in mice. C57Bl/6 wild type (WT) and iNOS genetically deficient (iNOS-KO) mice were subjected to upper incision tooth extraction, and alveolar bone healing was evaluated by micro-computed tomography (µCT) and histological/histomorphometric, birefringence, and molecular methods. RESULTS: The expression of iNOS had very low control conditions, whereas a significant increase is observed in healing sites of WT mice, where iNOS mRNA levels peak at 7d time point, followed by a relative decrease at 14d and 21d. Regarding bone healing, both WT and iNOS-KO groups showed the usual phases characterized by the presence of clots, granulation tissue development along the inflammatory cell infiltration, angiogenesis, proliferation of fibroblasts and extracellular matrix synthesis, bone neoformation, and remodeling. The overall micro-computed tomography and histomorphometric and birefringence analyses showed similar bone healing readouts when WT and iNOS-KO strains are compared. Likewise, Real-Time PCR array analysis shows an overall similar gene expression pattern (including bone formation, bone resorption, and inflammatory and immunological markers) in healing sites of WT and iNOS-KO mice. Moreover, molecular analysis shows that nNOS and eNOS were significantly upregulated in the iNOS-KO group, suggesting that other NOS isoforms could compensate the absence of iNOS. CONCLUSION: The absence of iNOS does not result in a significant modulation of bone healing readouts in iNOS-KO mice. The upregulation of nNOS and eNOS may compensate iNOS absence, explaining the similar bone healing outcome in WT and iNOS-KO strains.

Single-cell mapping of regenerative and fibrotic healing responses after musculoskeletal injury.

After injury, a cascade of events repairs the damaged tissue, including expansion and differentiation of the progenitor pool and redeposition of matrix. To guide future wound regeneration strategies, we compared single-cell sequencing of regenerative (third phalangeal element [P3]) and fibrotic (second phalangeal element [P2]) digit tip amputation (DTA) models as well as traumatic heterotopic ossification (HO; aberrant). Analyses point to a common initial response to injury, including expansion of progenitors, redeposition of matrix, and activation of transforming growth factor ß (TGF-ß) and WNT pathways. Surprisingly, fibrotic P2 DTA showed greater transcriptional similarity to HO than to regenerative P3 DTA, suggesting that gene expression more strongly correlates with healing outcome than with injury type or cell origin. Differential analysis and immunostaining revealed altered activation of inflammatory pathways, such as the complement pathway, in the progenitor cells. These data suggests that common pathways are activated in response to damage but are fine tuned within each injury. Modulating these pathways may shift the balance toward regenerative outcomes.

Risk Factors to Persistent Pain Following Musculoskeletal Injuries: A Systematic Literature Review.

BACKGROUND: Musculoskeletal (MSK) injury is one of the major causes of persistent pain. OBJECTIVE: This systematic literature review explored the factors that lead to persistent pain following a MSK injury in the general population, including athletes. METHODS: A primary literature search of five electronic databases was performed to identify cohort, prospective, and longitudinal trials. Studies of adults who diagnosed with a MSK injury, such as sprains, strains or trauma, were included. RESULTS: Eighteen studies involving 5372 participants were included in this review. Participants' ages ranged from 18-95 years. Most of the included studies were of prospective longitudinal design. Participants had a variety of MSK injuries (traumatic and non-traumatic) causing persistent pain. Multiple factors were identified as influencing the development of persistent pain following a MSK injury, including high pain intensity at baseline, post-traumatic stress syndrome, presence of medical comorbidities, and fear of movement. Scarcity of existing literature and the heterogeneity of the studies made meta-analysis not possible. CONCLUSIONS: This systematic review highlighted factors that might help predict persistent pain and disability following MSK injury in the general population, including athletes. Identification of these factors may help clinicians and other health care providers prevent the development of persistent pain following a MSK injury.

Exosomes from adipose-derived stem cells regulate M1/M2 macrophage phenotypic polarization to promote bone healing via miR-451a/MIF.

OBJECTIVES: Bone defects caused by diseases and trauma are usually accompanied by inflammation, and the implantation of biomaterials as a common repair method has also been found to cause inflammatory reactions, which affect bone metabolism and new bone formation. This study investigated whether exosomes from adipose-derived stem cells (ADSC-Exos) plays an immunomodulatory role in traumatic bone defects and elucidated the underlying mechanisms. METHODS: ADSC-Exos were loaded by a biomaterial named gelatine nanoparticles (GNPs), physical and chemical properties were analysed by zeta potential, surface topography and rheology. A rat model of skull defect was used for our in vivo studies, and micro-CT and histological staining were used to analyse histological changes in the bone defect area. RT-qPCR and western blotting were performed to verify that ADSC-Exos could regulate M1/M2 macrophage polarization. MicroRNA (miRNA) array analysis was conducted to determine the miRNA expression profiles of ADSC-Exos. After macrophages were treated with a miR-451a mimic, miR-451a inhibitor and ISO-1, the relative expression of genes and proteins was measured by RT-qPCR and western blotting. RESULTS: In vivo, micro-CT and histological staining showed that exosome-loaded GNPs (GNP-Exos) hydrogel, with good biocompatibility and strong mechanical adaptability, exhibited immunomodulatory effect mainly by regulating macrophage immunity and promoting bone tissue healing. Immunofluorescence further indicated that ADSC-Exos reduced M1 marker (iNOS) expression and increased M2 marker (CD206) expression. Moreover, in vitro studies, western blotting and RT-qPCR showed that ADSC-Exos inhibited M1 macrophage marker expression and upregulated M2 macrophage marker expression. MiR-451a was enriched in ADSC-Exos and targeted macrophage migration inhibitory factor (MIF). Macrophages treated with the miR-451a mimic showed lower expression of M1 markers. In contrast, miR-451a inhibitor treatment upregulated the expression of M1 markers and downregulated the expression of M2 markers, while ISO-1 (a MIF inhibitor) treatment upregulated miR-451a expression and downregulated M1 macrophage marker expression. CONCLUSION: GNP-Exos can effectively regulate bone immune metabolism and further promote bone healing partly through immune regulation of miR-451a, which may provide a therapeutic direction for bone repair.

Effects of non-Fourier bioheat transfer on bone drilling temperature in orthopedic surgery: Theoretical and in vitro experimental investigation.

The mechanical drilling process is a typical step in treating bone fractures to fix broken parts with screws and plates. Drilling generates a significant amount of heat and elevates the temperature of the bone, which can cause thermal osteonecrosis and damage to the surrounding bone tissue and nerves. Thermal inertia between heat flux and temperature gradient in nonhomogeneous interior structural medium-like biological tissues is arguable. Therefore, this paper proposes an analytical model of heat propagation in bone drilling for orthopedic surgery based on the hyperbolic Pennes bioheat transfer equation (HPBTE). Drilling experiments in bovine cortical bone samples were also carried out using an infrared thermography approach to confirm the proposed analytical model. Around the drilled hole surface, thermal necrosis is spread out from 1 to 10 mm. Increased feed rate reduces necrosis penetration distance and increases intense bone necrosis. The HPBTE includes thermal relaxation time effect and internal convective function of tissue perfusion rate. As these factors are not considered in the parabolic heat transfer equation (PHTE), the results show that the HPBTE is more accurate in predicting temperature and thermal osteonecrosis than the PHTE. As a result, proposed analytical model is a handy tool for calculating temperature to avoid thermal damage while improving process efficiency. Furthermore, it has the capability of controlling the manual or robotic drilling procedure for minimally invasive operations.

Evaluation of the effects of preconditioned human stem cells plus a scaffold and photobiomodulation administration on stereological parameters and gene expression levels in a critical size bone defect in rats.

We assessed the impact of photobiomodulation (PBM) plus adipose-derived stem cells (ASCs) during the anabolic and catabolic stages of bone healing in a rat model of a critical size femoral defect (CSFD) that was filled with a decellularized bone matrix (DBM). Stereological analysis and gene expression levels of bone morphogenetic protein 4 (BMP4), Runt-related transcription factor 2 (RUNX2), and stromal cell-derived factor 1 (SDF1) were determined. There were six groups of rats. Group 1 was the untreated control or DBM. Study groups 2-6 were treated as follows: ASC (ASC transplanted into DBM, then implanted in the CSFD); PBM (CSFD treated with PBM); irradiated ASC (iASC) (ASCs preconditioned with PBM, then transplanted into DBM, and implanted in the CSFD); ASC + PBM (ASCs transplanted into DBM, then implanted in the CSFD, followed by PBM administration); and iASC + PBM (the same as iASC, except CSFDs were exposed to PBM). At the anabolic step, all treatment groups had significantly increased trabecular bone volume (TBV) (24.22%) and osteoblasts (83.2%) compared to the control group (all, p = .000). However, TBV in group iASC + PBM groups were superior to the other groups (97.48% for osteoblast and 58.8% for trabecular bone volume) (all, p = .000). The numbers of osteocytes in ASC (78.2%) and iASC + PBM (30%) groups were remarkably higher compared to group control (both, p = .000). There were significantly higher SDF (1.5-fold), RUNX2 (1.3-fold), and BMP4 (1.9-fold) mRNA levels in the iASC + PBM group compared to the control and some of the treatment groups. At the catabolic step of bone healing, TBV increased significantly in PBM (30.77%), ASC + PBM (32.27%), and iASC + PBM (35.93%) groups compared to the control group (all, p = .000). There were significantly more osteoblasts and osteocytes in ASC (71.7%, 62.02%) (p = .002, p = .000); PBM (82.54%, 156%), iASC (179%, 23%), and ASC + PBM (108%, 110%) (all, p = .000), and iASC + PBM (79%, 100.6%) (p = .001, p = .000) groups compared to control group. ASC preconditioned with PBM in vitro plus PBM in vivo significantly increased stereological parameters and SDF1, RUNX2, and BMP4 mRNA expressions during bone healing in a CSFD model in rats.

The role of stem cell-derived exosomes in the repair of cutaneous and bone tissue.

Exosomes are extracellular vesicles secreted by various cell types, which play important roles in physiological processes. In particular, stem cell-derived exosomes have been shown to play crucial functions in intercellular communication during the tissue healing process. This review summarizes the effects of exosomes derived from different stem cell sources on the repair of cutaneous and bone tissue, focusing on the different pathways that could be involved in the regeneration process. The biogenesis, isolation, and content of exosomes have also been discussed. The effectiveness of exosomes is broadly demonstrated for skin and bone regeneration in animal models, supporting the basis for clinical translation of exosomes as a ready-to-use cell-free therapeutic for skin and bone regeneration.

"Do-not-touch" lesions of bone revisited.

Incidental bone lesions are encountered frequently in day-to-day practice. Many of these lesions are indeterminate requiring referral to specialist centres for further characterisation with or without biopsy; however, as biopsy has its own drawbacks, not all lesions can be subjected to biopsy. The primary role of a radiologist in these situations is to characterise these lesions based on their imaging appearances into aggressive lesions requiring biopsy and non-aggressive lesions that do not require a biopsy. The term "do-not-touch lesion" is used to describe a lesion with typical radiographic appearances that can be characterised based on radiographic appearances alone without needing a biopsy. With recent advances in imaging, many incidental lesions can be characterised into do-not-touch lesions based on their imaging appearances alone using a single imaging technique or using a combination of imaging techniques and, less frequently, with the additional help of serological investigations, without the need for biopsy. Hence, the definition of do-not-touch lesions of bone needs a revisit. In this article, we attempt to redefine do-not-touch lesions of bone and propose an imaging-based classification for characterisation of these lesions.

The first case of C4-Blast related death in Malaysia: A multidisciplinary approach illustrated with emphasis on conjoint anthropologic and radiologic expertise in forensic identification of skeletal remains.

BACKGROUND: Blast related deaths are often shrouded by diagnostic and medicolegal complexities requiring multidisciplinary expertise in order to gauge accurate identification of the victims and document scientific investigations comprehensively. In the advent of more sophisticated technology, anthropologic methods can now be applied into post mortem imaging interpretation. The traditional imaging roles of characterizing osseous fragmentation, detecting and localizing foreign bodies can be expanded to simulate and support physical anthropologic examination to assist in documentation for court proceedings. CASE PRESENTATION: An assemblage of unidentified, incomplete, highly fragmented skeletal remains were found scattered on a bare area of land in a forest. There was evidence of an explosion given the pattern of scattered evidentiary material of explosive and ballistic nature. Laboratory analysis of white powder found within the explosive material confirmed the presence of high impact C4-explosive trace containing cyclotrimethylene trinitramin [Royal Demolition Explosive (RDX)] & pentaerythritol tetranitrate (PETN). It took meticulous multidisciplinary efforts to confirm the identity of the victim that was marred by the severe fragmentation and skeletalization of the remains. The initial radiologic interpretation focused more on identification of foreign bodies and supporting documentation of fragmentation. With the current availability of post computed tomography (PMCT) in our center, we reexamined the value and potential of PMXR and PMCT as an adjunctive tool for biological profiling. CONCLUSION: This was the first case of C4-blast related death reported in Malaysia. The multidisciplinary approach in efforts to identify the victim may serve as a guide in managing, coordinating and maximizing the expertise of different forensic specialists, with emphasis on anthropologic and radiologic collaboration.

Is extracellular matrix (ECM) a promising scaffold biomaterial for bone repair?

The increasing demand for bone grafts and the scarcity of donors worldwide are promoting researchers to seek alternatives. The extracellular matrix (ECM) has been reported to enhance properties of osteoconduction and osteoinduction by simulating the molecular structure of bone and facilitating cell infiltration for bone repair. As one of several novel biomaterials, ECM has many desirable properties, including biocompatibility, bioactivity, and biosafety. Thus, we evaluated whether ECM is a promising scaffold biomaterial for bone repair. In this review, we explore ECM composition, the sources and fabrication methods, especially the decellularization technique, of ECM scaffolds. Furthermore, we highlight recent progress in the use of ECM as a scaffold biomaterial for bone repair. Generally, ECM is used in 1) three-dimensional (3D) cell cultures to promote osteogenic differentiation, 2) combinations with other biomaterials to increase their osteogenic effects, 3) 3D printing to produce customized or patient-tailored scaffolds for bone repair, and 4) hydrogels derived from ECM used for bone repair. In addition, we focus on future prospects for application of ECM as a scaffold material used for bone repair. From this review, we expect to have a perfect understanding of ECM-based scaffold materials in the hope that this leads to further research of the production of ECM biomaterials to meet the clinical needs for bone repair.

The gunshot-related injuries in trauma (GRIT) study: A profile of patients affected by gunshot-related orthopaedic injuries across South Africa.

BACKGROUND: South Africa (SA) has one of the highest gun-related mortality rates in the world - 20 people per day. The available data, however, do not reflect the substantial number of patients suffering non-lethal firearm injuries. Gunshot-related injury has been recognised as a highly costly healthcare problem by individual treating centres in SA and other countries; however, no 'national picture' has been examined in detail. OBJECTIVES: To explore the burden of gunshot-related orthopaedic injuries across SA. METHODS: A multicentre research network was established in SA, and 37 orthopaedic units across 9 provinces participated. A prospective, observational cohort study was performed during a 2-week period in 2019. Patients were screened, enrolled and reported by local orthopaedic teams. Patients were included if they had at least one acute gunshot-related orthopaedic fracture referred to the orthopaedic service. Patients were asked additional questions around baseline health-related quality-of-life (HRQOL) and personal circumstances. Follow-up was at 8 weeks after injury. RESULTS: Thirty-seven centres enrolled 135 patients over the 2-week study period. Western Cape Province had the highest number of reported cases (n=52; 39%), followed by Gauteng (n=35; 26%) and KwaZulu-Natal (n=29; 21%). The median age of patients was 30.5 years and the majority were male (89%). Forty-three percent of patients had been either shot or stabbed prior to this injury. Fifty-two percent of all patients required fracture fixation surgery and 11% required wound debridement without fracture fixation. HRQOL data were collected successfully at baseline, but follow-up data were available for <25% of cases. CONCLUSIONS: Gunshot-related orthopaedic injuries represent a significant burden of disease in the SA healthcare environment. This study highlights several areas for further research in the management of the injuries and associated outcomes.

Development of castor polyurethane scaffold (Ricinus communisL.) and its effect with stem cells for bone repair in an osteoporosis model.

The development of 'smart' scaffolds has achieved notoriety among current prospects for bone repair, especially for chronic osteopathy, such as osteoporosis. Millions of individuals in the world suffer from poor bone healing due to osteoporosis. The objective of this work was to produce and characterize castor polyurethane (PU) scaffolds (Ricinus communisL.)andevaluate itsin vitrobiocompatibility with stem cells and osteoinductive effectin vivoon bone failures in a leporid model of osteoporosis. The material was characterized using Fourier-transform infrared spectroscopy, thermogravimetric analysis, SEM, and porosity analysis. Then, the biocompatibility was assessed by adhesion using SEM and cytotoxicity in a 3-(4, 5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2H-tetrazolium assay. The osteoinductive effectin vivowas determined in bone defects in rabbit tibias (Oryctolagus cuniculus) submitted to castor PU scaffold, castor PU scaffold associated with stem cells, and negative control, after four and eight weeks, evaluated by computed microtomography and histopathology. The scaffolds were porous, with an average pore size of 209.5 ± 98.2 µm, absence of cytotoxicity, and positive cell adhesivenessin vitro.All the animals presented osteoporosis, characterized by multifocal osteoblastic inactivity and areas of mild fibrosis. There were no statistical differences between these treatments in the fourth week of treatment. In the eighth week, the treatment with castor PU scaffold alone induced more significant bone formation when compared to the other groups, followed by treatment with an association between castor PU scaffold and stem cells. The castor PU scaffold was harmless to cell culture, favoring cell adhesiveness and proliferation, in addition to inducing bone neoformation in osteoporotic rabbits.

Animal scavenging on pig cadavers in the Lowveld of South Africa.

Scavenging animals often scatter skeletal remains of forensic interest and leave bite marks. This study aimed to identify scavenging animals in the rural Lowveld of South Africa and to describe their scattering pattern and bite marks on bone. Ten pig cadavers (Sus scrofa domesticus) (40-80 kg) were placed at the Wits Rural Facility, Limpopo, South Africa during the summer and winter seasons. Motion activated cameras recorded the scavenging. Scavenger species were identified and their behaviors, scattering pattern, and bite marks were described. Scavenging was primarily by vultures (hooded, white-backed, and lappet-faced). Marabou stork, slender and banded mongoose, genet, civet, warthog and honey badger also actively scavenged. Vultures began to scavenge the pig cadavers after 18hrs in summer and between 26 and 28 h in winter and skeletonized pig cadavers rapidly between 5 and 98 min. Skeletonization occurred more rapidly and diffusely in summer while winter cases were densely scattered. Overall the scattered remains were within an area of 157.9 m2/1705.5 ft2 with a radius of 7.09 m/23.3 ft. Vultures cleaned bones thoroughly with very minimal markings - primarily nonspecific scores. The described scattering pattern and bite marks will assist in the recovery and analysis of scavenged remains.

The need for adaptable global guidance in health systems strengthening for musculoskeletal health: a qualitative study of international key informants.

BACKGROUND: Musculoskeletal (MSK) conditions, MSK pain and MSK injury/trauma are the largest contributors to the global burden of disability, yet global guidance to arrest the rising disability burden is lacking. We aimed to explore contemporary context, challenges and opportunities at a global level and relevant to health systems strengthening for MSK health, as identified by international key informants (KIs) to inform a global MSK health strategic response. METHODS: An in-depth qualitative study was undertaken with international KIs, purposively sampled across high-income and low and middle-income countries (LMICs). KIs identified as representatives of peak global and international organisations (clinical/professional, advocacy, national government and the World Health Organization), thought leaders, and people with lived experience in advocacy roles. Verbatim transcripts of individual semi-structured interviews were analysed inductively using a grounded theory method. Data were organised into categories describing 1) contemporary context; 2) goals; 3) guiding principles; 4) accelerators for action; and 5) strategic priority areas (pillars), to build a data-driven logic model. Here, we report on categories 1-4 of the logic model. RESULTS: Thirty-one KIs from 20 countries (40% LMICs) affiliated with 25 organisations participated. Six themes described contemporary context (category 1): 1) MSK health is afforded relatively lower priority status compared with other health conditions and is poorly legitimised; 2) improving MSK health is more than just healthcare; 3) global guidance for country-level system strengthening is needed; 4) impact of COVID-19 on MSK health; 5) multiple inequities associated with MSK health; and 6) complexity in health service delivery for MSK health. Five guiding principles (category 3) focussed on adaptability; inclusiveness through co-design; prevention and reducing disability; a lifecourse approach; and equity and value-based care. Goals (category 2) and seven accelerators for action (category 4) were also derived. CONCLUSION: KIs strongly supported the creation of an adaptable global strategy to catalyse and steward country-level health systems strengthening responses for MSK health. The data-driven logic model provides a blueprint for global agencies and countries to initiate appropriate whole-of-health system reforms to improve population-level prevention and management of MSK health. Contextual considerations about MSK health and accelerators for action should be considered in reform activities.

Age-related alterations and senescence of mesenchymal stromal cells: Implications for regenerative treatments of bones and joints.

The most common clinical manifestations of age-related musculoskeletal degeneration are osteoarthritis and osteoporosis, and these represent an enormous burden on modern society. Mesenchymal stromal cells (MSCs) have pivotal roles in musculoskeletal tissue development. In adult organisms, MSCs retain their ability to regenerate tissues following bone fractures, articular cartilage injuries, and other traumatic injuries of connective tissue. However, their remarkable regenerative ability appears to be impaired through aging, and in particular in age-related diseases of bones and joints. Here, we review age-related alterations of MSCs in musculoskeletal tissues, and address the underlying mechanisms of aging and senescence of MSCs. Furthermore, we focus on the properties of MSCs in osteoarthritis and osteoporosis, and how their changes contribute to onset and progression of these disorders. Finally, we consider current treatments that exploit the enormous potential of MSCs for tissue regeneration, as well as for innovative cell-free extracellular-vesicle-based and anti-aging treatment approaches.

3D-Printing Biodegradable PU/PAAM/Gel Hydrogel Scaffold with High Flexibility and Self-Adaptibility to Irregular Defects for Nonload-Bearing Bone Regeneration.

A three-dimensional (3D) printed biodegradable hydrogel scaffold with a strong self-expanding ability to conform to the contour of irregular bone defects and be closely adjacent to host tissues is reported herein. The scaffold has a triple cross-linked network structure consisting of photo-cross-linked polyacrylamide (PAAM) and polyurethane (PU) as the primary IPN network and chemical cross-linked gelatin (Gel) as the secondary network, which confers the scaffold with good mechanical properties. The addition of PU in the polymerization process of acrylamide (AAM) can improve the ultraviolet (UV) photocuring efficiency of the hydrogel and incorporate abundant hydrogen bonds between the PAAM copolymer chain and the PU chain. The results show that the hydrogel scaffold contains regular structures with smooth morphology, excellent dimensional stability, and uniform aperture. The degradation rate of the hydrogel scaffold is controllable through adjusting cross-linking agents and can be up to about 60% after degradation for 28 days. More importantly, the rapid self-inflating characteristic of the scaffold in water, that is, the volume of hydrogel scaffold can increase to about 8 times that of their own in an hour and can generate a slight compressive stress on the surrounding host tissue, thus stimulating the reconstruction and growth of new bone tissues. The in vitro experiment indicates that the scaffold is nontoxic and biocompatible. The in vivo experiment shows that the PU/PAAM/Gel chemically cross-linked scaffold displays the desirable osteogenic capability. This UV-curable 3D printed self-adaptive and degradable hydrogel scaffold holds great potential for nonload-bearing bone repair.

The Combination of Concentrated Growth Factor and Adipose-Derived Stem Cell Sheet Repairs Skull Defects in Rats.

BACKGROUND: The goal of this study was to create a biomaterial which combines concentrated growth factor (CGF) with an adipose-derived stem cell (ADSC) sheet to promote the repair of skull defects in rats. METHODS: We determined the optimal concentration of CGF extract by investigating the effects of different concentrations (0, 5%, 10%, and 20%) on the proliferation and differentiation of ADSCs. Then we created a complex combining CGF with an ADSC sheet, and tested the effects on bone repair in four experimental rat groups: (A) control; (B) ADSC sheet; (C) CGF particles; (D) combination of CGF + ADSCs. Eight weeks after the procedure, osteogenesis was assessed by micro-CT and hematoxylin and eosin staining. RESULTS: We found that the concentration of CGF extract that promoted optimal ADSC proliferation and differentiation in vitro was 20%. In turn, bone regeneration was promoted the most by the combination of CGF and ADSCs. CONCLUSION: In this study, we determined the optimal ratio of CGF and ADSCs to be used in a biomaterial for bone regeneration. The resulting CGF/ADSCs complex promotes maxillofacial bone defect repair in rats.