Formation Of Mature Lamellar Bone Research Articles

Heterotopic Ossification at Uncommon Sites: A Case Series of 4 Rare Cases

Heterotopic ossification (HO) is a condition of formation of mature lamellar bone in the extra skeletal soft tissue where bone does not usually exist. It is most commonly seen in muscle tissue and central nervous system following trauma. In this case series, we have reported 4 rare cases of heterotopic bone formations at uncommon sites. One case of HO in clear cell renal cell carcinoma, one case of HO in tendoachilles, one case of HO in intramuscular vascular malformation and one case HO in abdominal incision scar. HO is a rare entity. In most of the cases exact etiology is unknown. Further studies needed for more conclusive information regarding the clinical significance of heterotopic ossification.

Unveiling the time course mechanism of bone fracture healing by transcriptional profiles.

Bone fracture healing is a time-consuming and high-priority orthopedic problem worldwide. Discovering the potential mechanism of bone healing at a time course and transcriptional level may better help manage bone fracture. In this study, we analyze a time-course bone fracture-healing transcriptional data set in a rat model (GSE592, GSE594, and GSE1371) of Gene Expression Omnibus (GEO). RNA was obtained from female Sprague-Dawley rats with femoral fracture at the initial time (day 3) as well as early (week 1), middle (week 2), and late (week 4) time periods, with nonfracture rats used as control. Gene Ontology (GO) functional analysis and pathway examinations were performed for further measurements of GSEA and hub genes. Results indicated that the four stages of bone fracture healing at the initial, early, middle, and late time periods represent the phases of hematoma formation, callus formation, callus molding, and mature lamellar bone formation, respectively. Extracellular organization was positively employed throughout the four stages. At the hematoma formation phase, the muscle contraction process was downregulated. Antibacterial peptide pathway was downregulated at all phases. The upregulation of Fn1 (initial, early, middle, and late time periods), Col3a1 (initial, early, and middle time periods), Col11a1 (initial and early time periods), Mmp9 (middle and late time periods), Mmp13 (early, middle, and late time periods) and the downregulation of RatNP-3b (initial, early, middle, and late time periods) were possible symbols for bone fracture healing and may use as therapeutic targets. These findings suggest some new potential pathways and genes in the process of bone fracture healing and further provide insights that can be used in targeted molecular therapy for bone fracture healing.

Effectiveness of Prophylactic Interventions in Neurogenic Heterotopic Ossification (NHO): A Systematic Review.

Neurogenic heterotopic ossification (NHO) is the formation of mature lamellar bone in peri-articular tissues following a neurological insult, most commonly traumatic brain injury (TBI) or spinal cord injury (SCI). NHO is a debilitating condition associated with significant morbidity and reduced quality of life. However, its pathophysiology remains poorly understood. While surgery is the mainstay of treatment once NHO has been diagnosed, prophylactic options are limited and not well studied. This review aimed to determine the efficacy of various interventions used in the primary prevention of NHO. We conducted an electronic literature search using five databases (PubMed, Embase, ScienceDirect, Cochrane Library, and Cumulative Index to Nursing and Allied Health Literature (CINAHL)) for records published until April 10, 2022. We identified 2,610 potentially eligible records across all databases. Nine reports met our eligibility criteria and were included in this review. Four were clinical trials (three randomized control trials, one nonrandomized trial), four were observational studies, and one was a systematic review/meta-analysis. The medications/interventions used included: warfarin, pulse low-intensity electromagnetic field therapy (PLIMF), bisphosphonates, and nonsteroidal anti-inflammatory drugs (NSAIDs). We did not find conclusive evidence to recommend the use of bisphosphonates and warfarin in the prevention of NHO. On the contrary, we found NSAIDs and PLIMF as effective prophylactic options based on the results of high-quality randomized control trials. Further prospective randomized studies with prolonged follow-ups are needed to confirm the long-term efficacy of these preventive interventions.

Study on osteoinductive activity of biotin film by low-energy electron beam deposition.

Biotin film was prepared by low-energy electron beam deposition (LEBD). The molecular structure, chemical composition and micromorphology of the biotin film were investigated by 1HNMR, FTIR, XPS, AFM and SEM. The results showed the molecular structure of a monolayer of biotin film is fully consistent with the molecular structure of the initial biotin powders. The contact angle test showed that the biotin film exhibit good hydrophilicity. The release kinetics of biotin film was tested by UV-Vis method. It was found that the film was almost completely released in about two weeks. The cell viability of MC3T3-E1 cells on the surface of the biotin film was attaining 100.54±1.7% (P<0.05), showing excellent biocompatibility and biosafety. Titanium implant with surface of biotin film was implanted into the femoral head of rabbits as experimental group. The animals were euthanized after four weeks. Compared with the control group, mature lamellar bone formation was observed with dense trabecular bone, and the expression of Coll-I, Runx2 and BMP-2 was better. The results showed that the repair effect of bone defect in the experimental group was excellent.

Biomineralized Composite Liquid Crystal Fiber Scaffold Promotes Bone Regeneration by Enhancement of Osteogenesis and Angiogenesis.

Liquid crystals (LCs) are appealing biomaterials for applications in bone regenerative medicine due to their tunable physical properties and anisotropic viscoelastic behavior. This study reports a novel composite poly (L-lactide) (PLLA) scaffold that is manufactured by a simple electrospinning and biomineralization technique that precisely controls the fibrous structure in liquid LC phase. The enriched-LC composites have superior mineralization ability than neat PLLA; furthermore BMSC cells were inoculated onto the HAP-PLLA/LC with hydroxyapatite (HAP) composite scaffold to test the capability for osteogenesis in vitro. The results show that the PLLA/LC with HAP produced by mineralization leads to better cell compatibility, which is beneficial to cell proliferation, osteogenic differentiation, and expression of the angiogenic CD31 gene. Moreover, in vivo studies showed that the HAP-PLLA/LC scaffold with a bone-like environment significantly accelerates new and mature lamellar bone formation by development of a microenvironment for vascularized bone regeneration. Thus, this bionic composite scaffold in an LC state combining osteogenesis with vascularized activities is a promising biomaterial for bone regeneration in defective areas.

Cervical Ossification of Ligamentum Flavum: Elaborating anUnderappreciated but Occasional ContributortoMyeloradiculopathy in Aging PopulationBased onSynthesis of Individual Participant Data.

PurposeCervical ossification of ligamentum flavum (COLF) is a rare clinical entity which can occasionally contribute to severe myeloradiculopathy. Many orthopedists are unfamiliar with or underestimate this pathology. Therefore, a comprehensive research is obligatory to reappraise the epidemiological, radiological, clinical and histopathological characteristics of COLF-myeloradiculopathy based on synthesis of individual patient data.MethodsFollowing Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, PubMed, EMBASE, Scopus and Web of Science databases were searched for studies discussing COLF-myeloradiculopathy from the inception to December 2020.ResultsA total of 94 cases from 54 studies were identified. The annual publications demonstrated a steady increase, and most reports were from Japan and China. The mean age was 58.76±13.39 years and nearly 60% of cases occurred in the 55–64 and 65–74 years age group. The male-female ratio was 1.4:1. Most cases belonged to East Asian population (60.64%). COLF predominately appeared in the lower cervical and cervicothoracic spine (76.60%) and mainly affected C4-5 (23.29%) and C5-6 (21.23%). Single-segment type ossification accounted for 62.76 and 45.45% of ossification lesions distributed bilaterally. The majority of COLF (81.1%) were spontaneous, and motor disturbance (76.4%), spinal ataxia (62.5%) and sensory disturbance (58.9%) were the most common manifestations. Histopathologically, it’s a metaplastic process of endochondral ossification with the formation of mature lamellar bone which was distinguished from calcification of ligamentum flavum. About 21.28% of concurrent COLF and COPLL cases were identified as a separated group, with unique characteristics.ConclusionCOLF is an underappreciated but potentially growing pathogeny of myeloradiculopathy in aging population, though its distinct epidemiological, radiological, clinical and histopathological features are not fully supported by current evidence. However, our findings will provide several referential data for future researches to shed light on COLF.

Bone augmentation by replica-based bone formation

ObjectiveThe sources of iliac crest bone grafts are limited. Alternatives are evaluated due to the progress in biomaterial sciences. Synthetical hydroxyapatite (HA), ß-tricalcium phosphate (ß-TCP) or biphasic compounds, or even a mélange of HA and ß-TCP will replace bovine ceramics. The goal is maintenance of replica-based-bone formation (RBBF) for bone augmentation. Methods2 female and 2 male patients between 41 and 73 years with 5 sinus elevations were evaluated. Sinus elevations with lateral fenestration, trapezoidal-muco-periosteal flaps and filling with micro-chambered beads (1.5 mm) was performed. A porcine-collagenous membrane and the refixated flap covered the defect. A biopsy program over 20 months was confirm confirm the maintenance of the newly formed bone. ResultsA fast bone formation was pronounced. The biopsies revealed mature lamellar bone and full osseointegration of the ß-TCP implant. The biopsy after 20 months showed compact bone with osseointegration of minor rests of the ceramic implant. The defect revealed a mature bone stock already after 5 weeks. SignificanceThe introduction of the replica-based-bone formation (RBBF) around micro-chambered beads will change the paradigm of bone augmentation. The next step of the ongoing study has to redefine the interval for implant insertion.The clinical approach confirms the breakthrough to primary mature lamellar bone formation and will permit reduction of placement time for a dental implant.

Improved Osseointegration of a TiNbSn Alloy with a Low Young\u2019s Modulus Treated with Anodic Oxidation

Ti6Al4V alloy orthopedic implants are widely used as Ti6Al4V alloy is a biocompatible material and resistant to corrosion. However, Ti6Al4V alloy has higher Young’s modulus compared with human bone. The difference of elastic modulus between bone and titanium alloy may evoke clinical problems because of stress shielding. To resolve this, we previously developed a TiNbSn alloy offering low Young’s modulus and improved biocompatibility. In the present study, the effects of sulfuric acid anodic oxidation on the osseointegration of TiNbSn alloy were assessed. The apatite formation was evaluated with Scanning electron microscopy, X-ray diffraction, X-ray photoelectron spectroscopy and transmission electron microscopy analyses. The biocompatibility of TiNbSN alloy was evaluated in experimental animal models using pull-out tests and quantitative histological analyses. The results of the surface analyses indicated that sulfuric anodic oxidation induced abundant superficial apatite formation of the TiNbSn alloy disks and rods, with a 5.1-µm-thick oxide layer and submicron-sized pores. In vivo, treated rods showed increased mature lamellar bone formation and higher failure loads compared with untreated rods. Overall, our findings indicate that anodic oxidation with sulfuric acid may help to improve the biocompatibility of TiNbSn alloys for osseointegration.

Clinical analysis of 11 children with primary osteoma cutis

Objective To investigate clinical manifestations, pathological features and outcomes of primary osteoma cutis in children. Methods Eleven children with confirmed primary osteoma cutis diagnosed in Department of Dermatology, Beijing Children′s Hospital between 2011 and 2018 were included into this study. The clinical manifestations, histopathological features, and outcomes were analyzed retrospectively. Results Among the 11 patients, 7 were males and 4 were females. Primary osteoma cutis occurred within 22 months after birth in all the children, the median age of onset was 1 month, and the disease occurred during the first 6 months of life in 10 children. The skin lesions were characterized by skin-colored or reddish indurated papules, plaques or nodules of varying size with slight epidermal atrophy. Three patients had local skin lesions, and 8 had multiple skin lesions. Serum calcium and parathyroid hormone levels were within normal limits in all the children, and no developmental deformity was observed at birth in any of the children. Histopathological examination revealed the formation of mature lamellar bone in the dermis in all the cases, which involved the subcutaneous adipose tissue in 5 cases. The skin lesions became stable 8 - 18 months after the occurrence in 10 patients, which was consistent with primary plaque-like osteoma cutis. Only 1 patient underwent a slowly progressive course, and the skin lesions involved subcutaneous deep tissues, leading to dyskinesia, which was consistent with progressive osseous heteroplasia. Conclusions Primary osteoma cutis in children mostly occurs in infancy, whose clinical manifestations are atrophic, indurated plaques or nodules, and its main pathological feature is the formation of mature lamellar bone. Long-term follow-up is needed, and attention should be paid to the occurrence of progressive osseous heteroplasia. Key words: Ossification, heterotopic; Child; Osteoma cutis; Primary

Challenges of heterotopic ossification-Molecular background and current treatment strategies.

Heterotopic ossification (HO) is an abnormal formation of mature lamellar bone within extraskeletal soft tissues, such as muscles, tendons, and ligaments. This process is thought to be induced by inflammation associated with tissue injuries. HO is classified using two subtypes: resulting from injury or genetically inherited. HO formation is associated with polytrauma patients with traumatic brain injuries and spinal cord injuries. Moreover, HO is also considered to be a post-operative risk factor in some orthopaedic procedures. In this review, we summarize our current understanding of the pathology of different types of HO and discuss its current and future therapies. Thus far, research has revealed cellular and molecular pathways leading to HO formation and proposed several possible mechanisms leading to HO and conserved signalling pathways common in the different HO subtypes. Non-steroidal anti-inflammatory drug treatment and localized low-dose irradiation are currently the only available prophylactic treatments for HO. However, they are not always effective and do not target the osteogenic processes directly. New therapeutic strategies targeting the pathological processes of HO, such as bone morphogenetic protein (BMP) inhibitors like noggin, BMP type 1 receptor inhibitor, and nuclear retinoid acid receptor-gamma (RARγ) agonists, are currently being investigated. In-depth understanding of the HO pathological process could help to develop effective therapeutic strategies.

Mechanically enhanced lipo-hydrogel with controlled release of multi-type drugs for bone regeneration

Hydrogel is an excellent candidate in the field of drug delivery and tissue regeneration. However, hydrogel used as drug carriers is facing several problems including limited optional drug and burst drug release, besides hydrogel is still confronting some challenges in mechanical property involving decreased hydrogel's strength caused by interface separation between hydrogel and other solid composition. In this research, we designed a mechanical enhanced and release-controlling liposome modified hydrogel via hydrogen bone and hydrogel network micro-cross-linking double network as artificial scaffold for promoting the angiogenesis and osteogenesis in bone regeneration. Specifically, photo-cross linkable gelatin derivative (GelMA) was combined with drug loaded liposome by bonding effects, which lead to double improvement in mechanical property, such as compression, stretching, torsion and resiliency. Furthermore, the ability to control phased release was observed in the composite hydrogel including the early release of hydrophilic drug (deferoxamine), mid-term release of bioactive macromolecule (bovine serum albumin and bone morphogenetic protein 2) and long-term release of liposoluble medicine (paclitaxel). In vitro study revealed that, this composite hydrogel significantly promoted osteogenic and angiogenesis differentiation without significant influence on cell adhesion, proliferation. Finally, the composite hydrogel demonstrated a superior capacity in accelerating new and mature lamellar bone formation in distal femoral defect of Sprague-Dawley rats. Thus, the liposome modified hydrogel could supply a promising strategy for extending the application of hydrogel in drug delivery and tissue reconstruction.

Strontium Hydroxyapatite scaffolds engineered with stem cells aid osteointegration and osteogenesis in osteoporotic sheep model

Osteoporotic fracture healing is an orthopaedic challenge due to excessive bone resorption and impaired osteogenesis. Majority of current treatment strategies focus on regulating bone resorption and the potential application of Mesenchymal Stem Cells (MSCs) in promoting osteogenesis has not been explored much. Furthermore, the present study has put forth a novel approach, wherein the synergistic action of Strontium (Sr) and MSCs in a single implant may facilitate osteoporotic bone healing.Strontium Hydroxyapatite (SrHA) synthesized by wet precipitation was fabricated into tissue engineered Strontium incorporated Hydroxyapatite (cSrHA) using sheep adipose tissue derived MSCs (ADMSCs). Porosity, radiopacity and cytocompatibility of SrHA scaffolds were found appropriate for orthopaedic applications. cSrHA scaffolds exhibited an in vitro Alkaline Phosphatase activity of 20 μmol pnp/30 min comparable to that of Hydroxyapatite (HA) – control scaffold, proving its osteogenic efficacy. Implantation studies in sheep osteoporotic model depicted enhanced osteogenic ability with mature lamellar bone formation in cSrHA implanted group, compared to bare HA, SrHA and tissue engineered HA implanted groups. Histomorphometry data substantiated improved osteogenesis on par with material resorption, as cSrHA implanted group exhibited highest regeneration ratio of 0.38 ± 0.05. Density histograms from micro CT further signified the enhanced osteointegrative ability of cSrHA implants. Results of the study depicted the therapeutic potential of cSrHA in osteoporotic bone healing and proposes the use of allogenic ADMSCs for fabricating “Off the Shelf Tissue Engineered Products”.

Chitosan composite scaffold combined with bone marrow-derived mesenchymal stem cells for bone regeneration: in vitro and in vivo evaluation.

The study aimed to develop a chitosan (CS)-based scaffold for repairing calvarial bone defects. We fabricated composite scaffolds made of CS and bovine-derived xenograft (BDX), characterized their physicochemical properties including pore size and porosity, absorption, degradation, and compressive strength, compared their efficacy to support in vitro proliferation and differentiation of human jaw bone marrow-derived mesenchymal stem cells (hJBMMSCs), and evaluated their bone regeneration capacity in critical-size rat calvarial defects. The CS/BDX (mass ratio of 40:60) composite scaffold with porosity of 46.23% and pore size of 98.23 μm exhibited significantly enhanced compressive strength than the CS scaffold (59.33 ± 4.29 vs. 18.82 ± 2.49 Kpa). The CS/BDX (40:60) scaffold induced better cell attachment and promoted more osteogenic differentiation of hJBMMSCs than the CS scaffold. The CS/BDX (40:60) scaffold seeded with hJBMMSCs was the most effective in supporting new bone formation, as evidenced by better histomorphometry results, larger new bone area, and more obvious mature lamellar bone formation compared to other groups in rat calvarial defects 8 weeks after implantation. These results suggest that CS/BDX composite scaffold combining with hJBMMSCs has the potential for bone defect regeneration.

Inorganic Strengthened Hydrogel Membrane as Regenerative Periosteum.

Periosteum plays the pivotal role in neomineralization, vascularization and protection during bone tissue regeneration. However, many artificial periosteum focused only on protection and lacked of the osteogenesis and angiogenesis functional capacity. In this study, we developed a novelty inorganic strengthened gelatin hydrogel membrane via inorganic and organic co-cross-linked double network as artificial periosteum for enhancing the durable angiogenesis and osteogenesis in bone reconstruction. Mesoporous bioactive glass nanoparticles (MBGNs) chemically modified with photo-cross-linkable gelatin derivative (GelMA) were further incorporated into GelMA to fabricate an organic/inorganic co-cross-linked hydrogel membrane (GelMA-G-MBGNs). The GelMA-G-MBGNs hydrogel membrane displayed better mechanical property, durable degradation time, pH stable, biomineralization and long-term ion release. In vitro study demonstrated that, when compared with GelMA or GelMA/MBGNs, the GelMA-G-MBGN membrane significantly promoted osteogenic differentiation while maintaining stable local pH, which is conducive to cell adhesion and proliferation. Finally, the GelMA-G-MBGN membrane shows a superior artificial periosteum with superior capacity in angiogenesis and osteogenesis for accelerating new and mature lamellar bone formation in rat calvarial critical size defect. This co-cross-linked hydrogel membrane implied a promising strategy for the development of advanced periosteum biomaterials with excellent handle and bone repairing properties.

Traumatic Heterotrophic Ossification Of Quadriceps Femoris – A Case Report

Background - Formation  of mature lamellar bone  at unusual sites like soft tissues, which  normally does not exhibit properties of ossification is known as Heterotopic ossification (HO). It  has  a  multi-factorial  etiology with multiple risk factors. Trauma is one of such inciting event. Case report - We are reporting a rare case of Heterotopic ossification of right quadriceps femoris in a 26 year old young adult, with severe knee stiffness, with  no  improvement  following  conservative treatment, which was successfully treated with surgical excision, obtaining good clinical results. Key words - Heterotopic ossification, quadriceps femoris, knee stiffness, surgical excision

A Novel Method of Neo-osseous Flap Prefabrication: Induction of Free Calvarial Periosteum with Bioactive Glass.

Reconstruction of craniofacial bone defects is a primary focus of craniofacial surgery. Although autogenous bone grafts remain as the gold standard, alloplastic materials have also gained widespread popularity due to their off-the-shelf availability, ease of use, and durability. In addition to replacing the missing bone, some of these alloplastic materials have also been found to induce new bone formation. In this study, the phenomenon of neo-osseous induction with bioactive glass was investigated for different implant-soft tissue configurations. Thirty-two male, Wistar albino rats were divided into four equally numbered study groups. In group 1 (FP), adipofascial groin flaps were prefabricated with free periosteal grafts. In group 2 (FPB), adipofascial groin flaps were prefabricated with free periosteal grafts and bioactive glass. In group 3 (FB), adipofascial groin flaps were prefabricated with bioactive glass. In group 4 (control), adipofascial groin flaps were not prefabricated. Morphometric analyses of the prefabricated structures were performed using micro-CT. The histologic properties of the ectopic ossification were assessed by using a modified scoring system. Group 1 (FP) showed the greatest rate of mature lamellar bone formation. Group 2 (FBP) showed the greatest amount of bone density and volume. However, the addition of bioactive glass in group 2 (FBP) decreased the rate of mature lamellar bone formation when compared with group 1 (FP). Ectopic ossification was not observed in the control group. Bioactive glass can be successfully used in the prefabrication of vascularized compound structures for the reconstruction of complex bone defects. However, interference with the periosteal induction of mature lamellar bone formation should be taken into consideration, especially in pediatric bone defects, which primarily rely on spontaneous osteogenesis through periosteal induction.

Electrospun Yarn Reinforced NanoHA Composite Matrix as a Potential Bone Substitute for Enhanced Regeneration of Segmental Defects.

Nanohydroxyapatite (nanoHA) is a well-established synthetic bone substitute with excellent osteoconduction and osteointegration. However, brittleness coupled with slow degradation curtails its load-bearing and bone regeneration potential, respectively. To address these limitations, nanoHA composite matrix reinforced with electrospun fibrous yarns was fabricated and tested in vitro and in vivo. Different weight percentages (5, 10, 15 wt%) and varying lengths (short and continuous) of poly(l-lactic acid) yarns were randomly dispersed in a gelatinous matrix containing nanoHA. This significantly improved the compressive strength as well as work of fracture, especially for continuous yarns at high weight percentages (10 and 15 wt%). Incorporation of yarns did not adversely affect the pore size (50-350 μm) or porosity of the scaffolds as well as the in vitro cellular response. Finally, when tested in a critical-sized femoral segmental defect in rat, the nanocomposite scaffolds induced osteoblast cell infiltration at 2 months that subsequently underwent increased mature lamellar bone formation at 4 months, in both the mid and peripheral defect regions. Histomorphometric analysis demonstrated that new bone formation and biomaterial degradation were significantly enhanced in the composite scaffold when compared to commercially available HA. Overall, the composite matrix reinforced with electrospun yarns proved to be a potential bone substitute having an appropriate balance between mechanical strength, porosity, biodegradation, and bone regeneration ability.

Heterotopic ossification after hip arthroscopy.

Heterotopic ossification (HO) after hip arthroscopy is the abnormal formation of mature lamellar bone within extra skeletal soft tissues. HO may lead to pain, impaired range of motion and possibly revision surgery. There has been a substantial amount of recent research on the pathophysiology, prophylaxis and treatment of HO associated with open and arthroscopic hip surgery. This article reviews the literature on the aforementioned topics with a focus on their application in hip arthroscopy.

Adaptive immune response inhibits ectopic mature bone formation induced by BMSCs/BCP/plasma composite in immune-competent mice.

A combination of autologous bone marrow stromal cells (BMSCs) and biomaterials is a strategy largely developed in bone tissue engineering, and subcutaneous implantation in rodents or large animals is often a first step to evaluate the potential of new biomaterials. This study aimed at investigating the influence of the immune status of the recipient animal on BMSCs-induced bone formation. BMSCs prepared from C57BL/6 mice, composed of a mixture of mesenchymal stromal and monocytic cells, were combined with a biomaterial that consisted of biphasic calcium phosphate (BCP) particles and plasma clot. This composite was implanted subcutaneously either in syngenic C57BL/6 immune-competent mice or in T-lymphocyte-deficient Nude (Nude) mice. Using histology, immunohistochemistry, and histomorphometry, we show here that this BMSC/BCP/plasma clot composite implanted in Nude mice induces the formation of mature lamellar bone associated to hematopoietic areas and numerous vessels. Comparatively, implantation in C57BL/6 results in the formation of woven bone without hematopoietic tissue, a lower number of new vessels, and numerous multinucleated giant cells (MNGCs). In situ hybridization, which enabled to follow the fate of the BMSCs, revealed that BMSCs implanted in Nude mice survived longer than BMSCs implanted in C57BL/6 mice. Quantitative expression analysis of 280 genes in the implants indicated that the differences between C57BL/6 and Nude implants corresponded almost exclusively to genes related to the immune response. Gene expression profile in C57BL/6 implants was consistent with a mild chronic inflammation reaction characterized by Th1, Th2, and cytotoxic T-lymphocyte activation. In the implants retrieved from T-deficient Nude mice, Mmp14, Il6st, and Tgfbr3 genes were over-expressed, suggesting their putative role in bone regeneration and hematopoiesis. In conclusion, we show here that the T-mediated inflammatory microenvironment is detrimental to BMSCs-induced bone formation and shortens the survival of implanted cells. Conversely, the lack of T-lymphocyte reaction in T-deficient animals is beneficial to BMSCs-induced mature bone formation. This should be taken into account when evaluating cell/biomaterial composites in these models.

Optimization of reparative osteogenesis with using of calcium phosphate osteoplastic materials (literature review)

The analysis of domestic and foreign scientific sources on the possibilities of calcium phosphate osteoplastic materials for optimization of the reparative osteogenesis was done. It was found that different kinds of texture and geometric shapes of calcium phosphate osteoplastic materials make it possible to fill the defects of various configurations. Impregnation of granules, blocks and cylinders with hydrophilic surface with sterile physiological saline, autologous blood, blood products, bone marrow cells provide such texture of the material which might be easily modeled with a scalpel according to the shape of the defect, and thus it is useful in the surgical field. Synthetic nature of calcium phosphate materials ensures their safety in clinical practice, preventing the risk of infections, the occurrence of immune and genetic incompatibility, rejection reaction, suppuration, and allergic reactions. Xenografs of bovine bones also demonstrate safety concerning allergic reactions, bovine spongiform encephalopathy and other infections because of deproteinisation and high temperature processing (above 800 ºC) in time of their producing. Above all calcium-phosphate osteoplastic materials have osteoconductive, osteostimulative and secondary osteoinductive features, and impregnation of some implants with antibiotic allows to create on the site of implantation anti-bacterial and anti-inflammatory effects. Osteocondution caused by macro-, micropores and rough structure of osteoplastic materials, osteostimulation caused by their ability to adsorb growth factors on their surface and calcium ions from implants, and the secondary osteoinduction caused by bone morphogenetic proteins which absorb from tissue environment of the bone defect and blood on their surface or comprise to the implant. It was found that calcium phosphate osteoplastic materials are able to optimize angiogenesis, adhesion, proliferation of osteogenic cells and their differentiation into osteoblasts in the area of the defect and, consequently, newly development of bone tissue directly on the surface and in the cavities of the implant. It was shown that initially granulation tissue with blood vessels or osteoid, and after that trabecular mesh of woven bone tissue with a gradual formation of mature lamellar bone to be formed. Due to the phenomenon of precipitation and association with newly formed bone tissue of dissolved crystals of implanted calcium phosphate materials and activity of osteoblasts it is subjected to mineralization and remodeling resulting in the formation of bone tissue with architectonics which according to the law of Julius Wolff meets concrete functional load acting on bone. Simultaneously with bone formation due to the activity of osteoclasts and macrophages calcium phosphate osteoplastic materials are subjected to gradual resorption with speed ranging from some months to 11 years. The latter depends on many factors among which there are physical and chemical characteristics of material, size and structure of pores, geometrical shape, architectonics of the surface, impregnating substances before implantation, technical nuances of producing as well as type of bone which it implanted in. Different expressiveness of the above mentioned properties of implants must be considered in case of application in each clinical situation.