Stem Cells For Bone Regeneration Research Articles

The Use of Stem Cells in Bone Regeneration of Cleft Lip and Palate Patients: A Systematic Review.

Background and Objectives: Cleft lip alone or a combination of cleft lip and palate (CLP) is a common developmental abnormality in the craniofacial region. This umbrella review aims to identify promising avenues for treatment using stem cell therapy. Materials and Methods: Systematic reviews from 2014 to 2024 were searched among databases like PubMed, Medline, and Google Scholar. PRISMA guidelines were employed to ensure the thoroughness of the search. A quality assessment (ROBIS) of the included reviews was conducted to ensure the reliability and validity of the synthesized evidence. Results: Five systematic reviews were selected for this umbrella review. Results show that stem cell therapy, specifically using mesenchymal stem cells (MSCs) and adipocyte stem cells (ADSCs), promotes bone regeneration in CLP deformities. Although multiple studies have established the effectiveness of diverse types of stem cells in treating CLP, important considerations including safety concerns, methodological variability, and the need for standardization have been identified. The fact that the number of relevant systematic reviews that matched our inclusion criteria was limited could affect this research's robustness and may limit the breadth and depth of evidence synthesis. Definitive conclusions could not be reached due to variation among treatments and outcomes. Conclusions: The examined studies highlight the potential of stem cell therapy as a complementary approach to existing treatments for CLP. However, there are challenges that need to be addressed, including concerns regarding safety, variations in methodologies, and the need for standardization. Exploring the potential of other stem cell types may further enhance treatment outcomes for CLP patients.

EFFECT OF STEM CELL THERAPY ON BONE REPAIR OF THE MAXILLA AND MANDIBLE

Maxillary and mandibular defects can result from a number of issues, such as periodontal disease, tumors, trauma and congenital anomalies, and can affect not only speech and mastication, but also aesthetics and self-esteem. In this sense, stem cell therapy is a promising, effective and safe option in the growing search for new forms of treatment for these dysfunctions. In this context, the aim of this study is to evaluate, through a literature review, the use of stem cells in bone regeneration of the maxillary and mandibular bones. The information was obtained through a bibliographic search carried out in February and March 2024 on the Scielo, Pubmed, Medline and Google Scholar platforms using the descriptors "Stem Cells", "Bone Repair", "Mandible", "Maxilla" and their Portuguese versions. Only papers published in English and Portuguese that dealt with the use of stem cells to regenerate defects in the mandible and maxilla were selected. During the search, x papers were initially selected, which 18 were included after consulting the abstracts and then reading them in full. Mesenchymal stem cells have been shown to improve and accelerate healing processes and increase bone density in the long term, thus promoting a faster and more complete recovery for patients, reducing the need for autologous grafts or synthetic materials. However, they have been shown to have a limited effect in cases of extensive bone defects. It can be concluded that stem cell therapy is an effective and safe alternative for promoting bone regeneration in cases of maxillary and mandibular defects, but further controlled studies are still needed to improve its performance by developing more efficient application strategies.

Role of Adipose-Derived Mesenchymal Stem Cells in Bone Regeneration.

Bone regeneration involves multiple factors such as tissue interactions, an inflammatory response, and vessel formation. In the event of diseases, old age, lifestyle, or trauma, bone regeneration can be impaired which could result in a prolonged healing duration or requiring an external intervention for repair. Currently, bone grafts hold the golden standard for bone regeneration. However, several limitations hinder its clinical applications, e.g., donor site morbidity, an insufficient tissue volume, and uncertain post-operative outcomes. Bone tissue engineering, involving stem cells seeded onto scaffolds, has thus been a promising treatment alternative for bone regeneration. Adipose-derived mesenchymal stem cells (AD-MSCs) are known to hold therapeutic value for the treatment of various clinical conditions and have displayed feasibility and significant effectiveness due to their ease of isolation, non-invasive, abundance in quantity, and osteogenic capacity. Notably, in vitro studies showed AD-MSCs holding a high proliferation capacity, multi-differentiation potential through the release of a variety of factors, and extracellular vesicles, allowing them to repair damaged tissues. In vivo and clinical studies showed AD-MSCs favoring better vascularization and the integration of the scaffolds, while the presence of scaffolds has enhanced the osteogenesis potential of AD-MSCs, thus yielding optimal bone formation outcomes. Effective bone regeneration requires the interplay of both AD-MSCs and scaffolds (material, pore size) to improve the osteogenic and vasculogenic capacity. This review presents the advances and applications of AD-MSCs for bone regeneration and bone tissue engineering, focusing on the in vitro, in vivo, and clinical studies involving AD-MSCs for bone tissue engineering.

The Application and Research Progress of Hydrogel Loading Stem Cells in Bone Regeneration

The Application and Research Progress of Hydrogel Loading Stem Cells in Bone Regeneration

Effects of Oral Cavity Stem Cell Sources and Serum-Free Cell Culture on Hydrogel Encapsulation of Mesenchymal Stem Cells for Bone Regeneration: An In Vitro Investigation.

To develop a stem cell delivery model and improve the safety of stem cell transplantation for bone regeneration, this study aimed to determine the effects of stem cell sources, serum-free cell culture, and hydrogel cell encapsulation on the growth and osteogenic differentiation of mesenchymal stem cells (MSCs) from the oral cavity. The study groups were categorized according to stem cell sources into buccal fat pad adipose (hBFP-ADSCs) (Groups 1, 4, and 7), periodontal ligament (hPDLSCs) (Groups 2, 5, and 8), and dental pulp-derived stem cells (hDPSCs) (Groups 3, 6, and 9). MSCs from each source were isolated and expanded in three types of sera: fetal bovine serum (FBS) (Groups 1-3), human serum (HS) (Groups 4-6), and synthetic serum (SS) (StemPro™ MSC SFM) (Groups 7-9) for monolayer (m) and hydrogel cell encapsulation cultures (e). Following this, the morphology, expression of MSC cell surface antigens, growth, and osteogenic differentiation potential of the MSCs, and the expression of adhesion molecules were analyzed and compared. SS decreased variations in the morphology and expression levels of cell surface antigens of MSCs from three cell sources (Groups 7m-9m). The levels of osteoblastic differentiation of the hPDLSCs and hBFP-ADSCs were increased in SS (Groups 8m and 7m) and the cell encapsulation model (Groups 1e, 4e, 7e-9e), but the promoting effects of SS were decreased in a cell encapsulation model (Groups 7e-9e). The expression levels of the alpha v beta 3 (ITG-αVβ3) and beta 1 (ITG-β1) integrins in the encapsulated cells in FBS (Group 1e) were higher than those in the SS (Group 7e). Human PDLSCs and BFP-ADSCs were the optimum stem cell source for stem cell encapsulation by using nanohydroxyapatite-calcium carbonate microcapsule-chitosan/collagen hydrogel in serum-free conditions.

Therapy with bone marrow mesenchymal stem cells in bone regeneration in children with osteonecrosis secondary to sickle cell disease.

This study aimed to describe the evolution of bone regeneration in children with hip osteonecrosis associated with sickle cell disease, treated with bone marrow-derived mesenchymal stem cell implants at the Professor Edgar Santos University Hospital Complex. A non-randomized clinical trial was conducted with 48 patients of both sexes, aged between 11 and 18years, diagnosed with femoral head osteonecrosis secondary to sickle cell disease. Patient selection was based on strict criteria, including confirmed diagnosis of sickle cell anemia and a stage of osteonecrosis compatible with the proposed treatment. Bone regeneration assessment was performed through radiographic examinations and magnetic resonance imaging, following the Ficat & Arlet criteria and the Salter-Thompson classification. Statistical analysis revealed a significant association between the patients' age and positive treatment outcomes, suggesting that autologous bone marrow cell implantation is a safe and effective approach in the early stages of osteonecrosis. The majority of patients (87.5%) reported complete pain relief, while 10.42% experienced significant symptom improvement. Only one patient (2.08%) did not observe improvement. The results indicate that cell therapy can regenerate or slow the progression of bone necrosis, reducing the need for more invasive surgical procedures. The study demonstrates the potential of bone marrow-derived mesenchymal stem cell implantation in treating hip osteonecrosis in children with sickle cell disease, emphasizing the importance of long-term monitoring of bone structure stability.

Discovery of multipotent progenitor cells from human induced membrane: Equivalent to periosteum-derived stem cells in bone regeneration

BackgroundThe periosteum stem cells (PSCs) plays a critical role in bone regeneration and defect reconstruction. Insertion of polymethyl methacrylate (PMMA) bone cement can form an induced membrane(IM) and showed promising strategy for bone defect reconstruction, the underlying mechanism remains unclear. Our study sought to determine whether IM-derived cells(IMDCs) versus PSCs have similar characteristics in bone regeneration. MethodsIM and periosteum were harvested from ten bone defect patients treated with PMMA, the IMDCs and PSCs were isolated respectively. Morphological, functional and molecular evaluation was performed and matched for comparison. ResultsBoth progenitor-like IMDCs and PSCs were successfully isolated. In vitro, we found IMDCs were similar to PSCs in morphology, colony forming capacity and expression of surface marker(CD90+, CD73+, CD105+, CD34-/CD45-). Meanwhile, these IMSCs displayed multipotency with chondrogenic, adipogenic and osteogenic differentiation, but differed in some IMSCs(3/10) population showing relatively poor osteogenic differentiation. The molecular profiles suggests that cell cycle and DNA replication signaling pathways were associated with these varying osteogenic potential. In vivo, we established a cell-based tissue-engineered bone by seeding IMDSs/PSCs to demineralized bone matrix (DBM) scaffold and demonstrated both IMDSs and PSCs enhanced bone regeneration in SCID mice bone defect model compared with DBM alone. ConclusionOur data demonstrated IM containing multipotent progenitor cells similar to that periosteum promoting bone regeneration, and indicated the existence of multiple subsets in osteogenic differentiation. Overall, the study provided a cellular and molecular insights in understanding the successful or failed outcome of bone defect healing.The translational potential of this article: This study confirmed IMDCs and PSCs share similar regeneration capacity and inform a translation potential of that cellular therapy applying IMDCs in bone defect repair.

Macrophages-bone marrow mesenchymal stem cells crosstalk in bone healing.

Bone healing is associated with many orthopedic conditions, including fractures and osteonecrosis, arthritis, metabolic bone disease, tumors and periprosthetic particle-associated osteolysis. How to effectively promote bone healing has become a keen topic for researchers. The role of macrophages and bone marrow mesenchymal stem cells (BMSCs) in bone healing has gradually come to light with the development of the concept of osteoimmunity. Their interaction regulates the balance between inflammation and regeneration, and when the inflammatory response is over-excited, attenuated, or disturbed, it results in the failure of bone healing. Therefore, an in-depth understanding of the function of macrophages and bone marrow mesenchymal stem cells in bone regeneration and the relationship between the two could provide new directions to promote bone healing. This paper reviews the role of macrophages and bone marrow mesenchymal stem cells in bone healing and the mechanism and significance of their interaction. Several new therapeutic ideas for regulating the inflammatory response in bone healing by targeting macrophages and bone marrow mesenchymal stem cells crosstalk are also discussed.

A Calvarial Defect Model to Investigate the Osteogenic Potential of Umbilical Cord Stem Cells in Bone Regeneration.

The standard graft material for alveolar cleft repair (ACR) is autogenous iliac crest. A promising alternative potential graft adjunct-newborn human umbilical cord mesenchymal stem cells (h-UCMSCs)-has yet to be explored in vivo. Their capacity for self-renewal, multipotent differentiation, and proliferation allows h-UCMSCs to be harnessed for regenerative medicine. This study sought to evaluate the efficacy of using tissue-derived h-UCMSCs and their osteogenic capabilities to improve ACR in a murine model. Foxn1 mice were separated into three groups with the following calvarial defects: no treatment (empty defect; n = 6), poly(D,L-lactide-co-glycolide) (PLGA) scaffold ( n = 6), or h-UCMSCs with PLGA ( n = 4). Bilateral 2-mm-diameter parietal bone critical-sized defects were created using a dental drill. Microcomputed tomography (microCT) imaging was performed 1, 2, 3, and 4 weeks postoperatively. The mice were euthanized 4 weeks postoperatively for RNAScope, immunohistochemical, and histological analysis. No mice experienced complications during the follow-up period. MicroCT imaging and histological analysis demonstrated that the no-treatment and PLGA-only defects remained patent without significant defect size differences across groups. In contrast, the h-UCMSCs with PLGA group had significantly greater bone fill on microCT and histological analysis. This study demonstrates a successful calvarial defect model for the investigation of h-UCMSC-mediated osteogenesis and bone repair. Evidence reveals that PLGA alone has neither short-term effects on bone formation nor any unwanted side effects, making it an attractive scaffold. Further investigation using h-UCMSCs with PLGA in larger animals is warranted to advance future translation to patients requiring ACR. The authors' results demonstrate a successful murine calvarial defect model for the investigation of h-UCMSC-mediated osteogenesis and bone repair, and they provide preliminary evidence for the safe and efficacious use of this graft adjunct in alveolar cleft repair.

Potential of Oral Cavity Stem Cells for Bone Regeneration: A Scoping Review

Bone loss is a common problem that ranges from small defects to large defects after trauma, surgery, or congenital malformations. The oral cavity is a rich source of mesenchymal stromal cells (MSCs). Researchers have documented their isolation and studied their osteogenic potential. Therefore, the objective of this review was to analyze and compare the potential of MSCs from the oral cavity for use in bone regeneration. Methods: A scoping review was carried out following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) guidelines. The databases reviewed were PubMed, SCOPUS, Scientific Electronic Library Online (SciELO), and Web of Science. Studies using stem cells from the oral cavity to promote bone regeneration were included. Results: A total of 726 studies were found, of which 27 were selected. The MSCs used to repair bone defects were (I) dental pulp stem cells of permanent teeth, (II) stem cells derived from inflamed dental pulp, (III) stem cells from exfoliated deciduous teeth, (IV) periodontal ligament stem cells, (V) cultured autogenous periosteal cells, (VI) buccal fat pad-derived cells, and (VII) autologous bone-derived mesenchymal stem cells. Stem cells associate with scaffolds to facilitate insertion into the bone defect and to enhance bone regeneration. The biological risk and morbidity of the MSC-grafted site were minimal. Successful bone formation after MSC grafting has been shown for small defects with stem cells from the periodontal ligament and dental pulp as well as larger defects with stem cells from the periosteum, bone, and buccal fat pad. Conclusions: Stem cells of maxillofacial origin are a promising alternative to treat small and large craniofacial bone defects; however, an additional scaffold complement is required for stem cell delivery.

Success and use of Stem Cells in Bone Regeneration of the Oral Cavity Systematic Review

Tissue engineering using mesenchymal stem cells (MSCs) is a recent therapy modality that has multiple advantages. One of them is the ability to accelerate hard and soft tissue repair processes thanks to, in part, its proliferative and regenerative capacities, improving morbidity postoperative of the patients. Therefore, the main objective of this review system is to be able to identify the current uses of MSCs in regenerative therapies bones of the oral cavity. In recent years, various articles have been published in where we talk about the advances that have been made in regenerative treatments. The regeneration of lost oral tissues is the objective of research in MSCs. For this reason, it is important that the main characteristics of therapies with MSCs are understood by clinicians so that they can be used in the future. Objective: To describe the success and use of MSCs for bone regeneration of the oral cavity. Material and method: A search in the PUBMED, STEM CELLS databases JOURNAL and MICROSOFT ACADEMIC was made to include clinical studies (randomized and controlled), case controls or series of cases that describe the use of human mesenchymal cells (MSC’s) for bone regeneration surgeries in the oral cavity, specifically. Results: 147 articles were found, after reading the title and abstracts 107 articles were selected, 99 were eliminated after evaluating inclusion criteria and exclusion, 8 articles were selected to carry out a complete reading of the text. The selected articles are: 2 randomized clinical cases, 3 cases nonrandomized controlled trials and 3 case series reports. the site for obtaining MSCs that used the most corresponds to the bone marrow. with the results of the articles included in this study, it is observed that the mesenchymal cells intraoral would have the capacity to carry out new formation of bone tissue. Conclusion: It is necessary to specify a storage and transport protocol for the MSCs. Studies using MSCs extracted from other donor sites are lacking. intraoral. Good results were found in tissue regenerative treatments bone tissue incorporating cellular technology into its procedures.

Identification and characterization of NFATc1+ skeletal stem cells in bone regeneration.

Skeletal stem cells (SSCs) fuel adult bone with stemness resources to maintain homeostasis and support regeneration, which depends on the precise determination of the osteogenic lineage commitment of SSCs. In this study, using Cre-loxP reporter lineage tracking, we identified and characterized a population of NFATc1+ SSCs in bone regeneration. Pre-existing NFATc1+ SSCs are involved in early bone callus formation. Subsequently, these NFATc1+ SSCs produce osteolineage descendants in the subsequent stages of regeneration. The Ca2+-triggered transcriptional activity of NFATc1 constitutes the pre-imprinted memory of the trajectory to intrinsically orchestrate osteogenesis of SSCs. Inhibition of Ca2+/NFATc1 signaling in SSCs directly impairs osteogenesis and bone regeneration. In summary, our findings provide a mechanistic understanding of adult bone regeneration through the regulation of NFATc1+ SSCs.

Nanotopographical 3D-Printed Poly(ε-caprolactone) Scaffolds Enhance Proliferation and Osteogenic Differentiation of Urine-Derived Stem Cells for Bone Regeneration.

3D-printing technology can be used to construct personalized bone substitutes with customized shapes, but it cannot regulate the topological morphology of the scaffold surface, which plays a vital role in regulating the biological behaviors of stem cells. In addition, stem cells are able to sense the topographical and mechanical cues of surface of scaffolds by mechanosensing and mechanotransduction. In our study, we fabricated a 3D-printed poly(ε-caprolactone) (PCL) scaffold with a nanotopographical surface and loaded it with urine-derived stem cells (USCs) for application of bone regeneration. The topological 3D-printed PCL scaffolds (TPS) fabricated by surface epiphytic crystallization, possessed uniformly patterned nanoridges, of which the element composition and functional groups of nanoridges were the same as PCL. Compared with bare 3D-printed PCL scaffolds (BPS), TPS have a higher ability for protein adsorption and mineralization in vitro. The proliferation, cell length, and osteogenic gene expression of USCs on the surface of TPS were significantly higher than that of BPS. In addition, the TPS loaded with USCs exhibited a good ability for bone regeneration in cranial bone defects. Our study demonstrated that nanotopographical 3D-printed scaffolds loaded with USCs are a safe and effective therapeutic strategy for bone regeneration.

Use of stem cells in bone regeneration in cleft palate patients: review and recommendations.

This study was conducted to review the efficacy of different sources of stem cells in bone regeneration of cleft palate patients. The majority of previous studies focused on the transplantation of bone marrow mesenchymal stem cells. However, other sources of stem cells have also gained considerable attention, and dental stem cells have shown especially favorable outcomes. Additionally, approaches that apply the co-culture and co-transplantation of stem cells have shown promising results. The use of different types of stem cells, based on their accessibility and efficacy in bone regeneration, is a promising method in cleft palate bone regeneration. In this regard, dental stem cells may be an ideal choice due to their efficacy and accessibility. In conclusion, stem cells, despite the lengthy procedures required for culture and preparation, are a suitable alternative to conventional bone grafting techniques.

Efficacy of Application of Periodontal Ligament Stem Cells in Bone Regeneration: A Systematic Review of Animal Studies

Introduction: We aimed to systematically review the animal studies that have investigated the efficacy of periodontal ligament stem cells (PDLSCs) in bone regeneration. Methods: Web of science, Scopus, PubMed, Embase, Cochrane Library, and ProQuest were searched to September 2022 for animal studies investigating bone regeneration using PDLSCs. Results: Twenty studies were included. Calvaria and alveolar defects were treated with stem cells. The cells were mainly carried with hydrogel, hydroxyapatite, and collagen scaffolds. PDLSCs promoted osteogenesis compared with cell-free scaffolds, except in one study where biphasic calcium phosphate block scaffolds alone or with Bone morphogenic protein 2 had superior outcomes in calvaria defects. Controversial results were reported when comparing the osteogenic potential of PDLSCs and bone marrow stem cells. Two studies reported higher potential in BMSCs, and two others reported higher bone formation and more bone quality in PDLSCs. Conclusion: With the limitations of this study, PDLSCs might have promising potential to accelerate bone regeneration in artificial defects; however, due to high heterogeneity in the outcomes of the present studies, before moving forward to human experiments, further preclinical in vivo studies are needed.

Application of Human Adipose-Derived Stem cells for Bone Regeneration of the Skull in Humans.

Archeological archives report cranioplasty as 1 of the oldest surgical procedures; however, it was not until the last century that true advances have been made. Alternative approaches are necessary to achieve optimal closure of the defect with fewer adverse effects. We aim to evaluate the use of human adipose-derived stem cells (hADSCs) alone or seeded in scaffolds as the main treatment for cranial bone defects and to assess human patient outcomes. A systematic review was performed by querying PubMed, Ovid MEDLINE, EMBASE, and Cumulative Index to Nursing and Allied Health Literature databases with the MeSH terms: "adipose-derived stem cells," "cranial bone defect," "stromal vascular factor," "fat grafting," as well as synonyms in combinations determined by our search strategy. We included human models that used hADSCs as primary therapy. We excluded studies in languages other than English. One hundred ninety-four studies were identified after removal of duplicates. Four articles that used hADSCs as the main therapy to treat calvarial defects in humans were included. One article applied the cell therapy alone, and 3 used β-tricalcium phosphate granules as a scaffold to seed the hADSCs. Bone regeneration was reached in a short and intermediate period using autologous hADSCs in humans with no major adverse effects in all 4 articles included. A long-term follow-up study (6 years) exhibited late infections and reabsorption of the β-tricalcium phosphate scaffold seeded with hADSCs.

Use of mesenchymal stem cells for guided bone regeneration in the dental setting: a review

The use of mesenchymal stem cells for bone regeneration in the oral cavity due to its differentiation capacity is part of the most promising scientific advances in regenerative medicine. The knowledge about this cell therapy obtained in recent times has been raising the expectations of health professionals; however there is still much to discover. The objective was to analyze the current evidence on the use of stem cells for guided bone regeneration in the dental field, through the bibliographic search of 30 indexed publications in Spanish and English registered from 2010 to 2020 in the databases: scielo , pubmed and academic google. The results demonstrated its effectiveness in planned bone regeneration in specialties such as periodontics and maxillofacial surgery; however, more research and the search for solutions are still required to facilitate its obtaining, maintenance and cultivation. In addition, it is necessary to know its indications and contraindications for a successful treatment.

Increased Expression of miR-7a-5p and miR-592 during Expansion of Rat Dental Pulp Stem Cells and Their Implication in Osteogenic Differentiation

Dental pulp stem cells (DPSCs) possess strong osteogenic differentiation potential and are promising cell sources in regenerative medicine. However, such differentiation capacity progressively declines during their in vitro expansion. MicroRNAs (miRNAs) play important roles in modulating stem cell differentiation. This study aimed (1) to determine if miR-7a-5p and miR-592 are involved in maintaining and regulating osteogenic differentiation of DPSCs, and (2) to explore their potential regulatory pathways. We found that the expression of miR-7a-5p and miR-592 was significantly upregulated during the expansion of rat DPSCs (rDPSCs). Overexpression of these miRNAs inhibited the osteogenic/odontogenic differentiation of rDPSCs, as evidenced by calcium deposition and osteogenic/odontogenic gene expression. RT-qPCR determined that miR-592 could downregulate heat shock protein B8, whose expression is reduced during the expansion of rDPSCs. Furthermore, RNA-seq and bioinformatics analysis identified significant signaling pathways of miR-7a-5p and miR-592 in regulating osteogenic differentiation, including TNF, MAPK, and PI3K-Akt pathways. We conclude that upregulating miR-7a-5p and miR-592 suppresses the osteogenic differentiation of rDPSCs during their in vitro expansion, likely via TNF, MAPK, and PI3K-Akt pathways. The results may shed light on application of miR-7a-5p and miR-592 for maintaining osteo-differentiation potential in stem cells for bone regeneration and bone-related disease treatment.

Bone marrow aspirate: a viable source of stem cells for bone regeneration. A systematic review

This systematic review evaluated the effectiveness of bone marrow aspirate (BMA) to enhance bone repair in humans. Comprehensive survey of ramdomized clinical trials published up to June 2021 and listed in PubMed/MEDLINE, EMBASE, and Cochrane Library databases following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Two reviewers independently searched eligible studies, made a final article selection, and extracted the data of the selected studies to evaluate it qualitatively. Overall, 13 studies were included in the review. Experimental models involved Posttraumatical aseptic nonunions of long bones of the upper limb, alveolar ridges following tooth extraction, atrophic mandibular fracture, benign bone lesions, bilateral tibial lengthening, fracture of intracapsular neck femur, maxillary horizontal ridge augmentation, non-traumatic femoral head necrosis, and sinus maxillary augmentation. The analyses included radiography, tomography, biopsies, and clinical evaluations. Ten studies reported enahanced bone formation (primary outcome) with combined use or not of BMA with other biomaterials and three studies found no benefit resulting from the use of BMA to treat bony defects. Secundary outcomes related to the healing process were also evaluated and positive, such as postoperative complications and pain visual analogue score. Within the limits of the present study, it can be concluded that BMA can improve the early stages of bone healing process.

Comparison of Autologous Blood Clots with Fibrin Sealant as Scaffolds for Promoting Human Muscle-Derived Stem Cell-Mediated Bone Regeneration.

Background. Fibrin sealant has been used as a scaffold to deliver genetically modified human muscle-derived stem cells (hMDSCs) for bone regeneration. Alternatively, autologous blood clots are safe, economic scaffolds. This study compared autologous blood clot (BC) with fibrin sealant (FS) as a scaffold to deliver lenti-BMP2/GFP-transduced hMDSCs for bone regeneration. Methods. In vitro osteogenic differentiation was performed using 3D pellet culture and evaluated using microCT and Von Kossa staining. The lenti-GFP transduced cells were then mixed with human blood for evaluation of osteogenic differentiation. Furthermore, a murine critical- sized calvarial defect model was utilized to compare BC and FS scaffolds for lenti-BMP2/GFP-transduced hMDSCs mediated bone regeneration and evaluated with micro-CT and histology. Results. Lenti-BMP2/GFP transduced hMDSCs formed significantly larger mineralized pellets than non-transduced hMDSCs. hMDSCs within the human blood clot migrated out and differentiated into ALP+ osteoblasts. In vivo, BC resulted in significantly less new bone formation within a critical-sized calvarial bone defect than FS scaffold, despite no difference observed for GFP+ donor cells, osteoclasts, and osteoblasts in the newly formed bone. Conclusions. Human lenti-BMP2/GFP-transduced hMDSCs can efficiently undergo osteogenic differentiation in vitro. Unexpectedly, the newly regenerated bone in BC group was significantly less than the FS group. The autologous blood clot scaffold is less efficacious for delivering stem cells for bone regeneration than fibrin sealant.