scholarly journals Bioactive Factors-imprinted Scaffold Vehicles for Promoting Bone Healing: The Potential Strategies and the Confronted Challenges for Clinical Production

2020 ◽  
Vol 1 (1) ◽  
pp. 37-54
Author(s):  
Peng-Peng Xue ◽  
Jian-dong Yuan ◽  
Qing Yao ◽  
Ying-Zheng Zhao ◽  
He-Lin Xu
Keyword(s):  
Bone Morphogenetic Proteins ◽  
Bone Healing ◽  
Half Life ◽  
Wound Repair ◽  
Large Scale ◽  
Bone Repair ◽  
Callus Formation ◽  
Fracture Repair ◽  
Enzyme Degradation

Abstract Wound repair of bone is a complicated multistep process orchestrated by inflammation, angiogenesis, callus formation, and bone remodeling. Many bioactive factors (BFs) including cytokine and growth factors (GFs) have previously been reported to be involved in regulating wound healing of bone and some exogenous BFs such as bone morphogenetic proteins (BMPs) were proven to be helpful for improving bone healing. In this regard, the BFs reported for boosting bone repair were initially categorized according to their regulatory mechanisms. Thereafter, the challenges including short half-life, poor stability, and rapid enzyme degradation and deactivation for these exogenous BFs in bone healing are carefully outlined in this review. For these issues, BFs-imprinted scaffold vehicles have recently been reported to promote the stability of BFs and enhance their half-life in vivo. This review is focused on the incorporation of BFs into the modulated biomaterials with various forms of bone tissue engineering applications: firstly, rigid bone graft substitutes (BGSs) were used to imprint BFs for large scale bone defect repair; secondly, the soft sponge-like scaffold carrying BFs is discussed as filling materials for the cavity of bone defects; thirdly, various injectable vehicles including hydrogel, nanoparticles, and microspheres for the delivery of BFs were also introduced for irregular bone fracture repair. Meanwhile, the challenges for BFs-imprinted scaffold vehicles are also analyzed in this review.

scholarly journals Image-Based Radiodensity Profilometry Measures Early Remodeling at the Bone-Callus Interface in Sheep

2021 ◽  
Author(s):  
Tianyi Ren
Keyword(s):  
Bone Healing ◽  
Callus Formation ◽  
Early Stage ◽  
Numerical Models ◽  
Fracture Repair ◽  
Density Gradients ◽  
Intact Bone ◽  
Processing Techniques ◽  
Early Healing

Bone healing has been traditionally described as a four-phase process: inflammatory response, soft callus formation, hard callus development, and remodeling. The remodeling phase has been largely neglected in most numerical mechanoregulation models of fracture repair in favor of capturing early healing using a pre-defined callus domain. However, in vivo evidence suggests that remodeling occurs concurrently with repair and causes changes in cortical bone adjacent to callus that are typically neglected in numerical models of bone healing. The objective of this study was to use image processing techniques to quantify this early-stage remodeling in ovine osteotomies. To accomplish this, we developed a numerical method for radiodensity profilometry with optimization-based curve fitting to mathematically model the bone density gradients in the radial direction across the cortical wall and callus. After assessing data from 26 sheep, we defined a dimensionless density fitting function that revealed significant remodeling occurring in the cortical wall adjacent to callus during early healing, a 23% average reduction in density compared to intact. This fitting function is robust for modeling radial density gradients in both intact bone and fracture repair scenarios and can capture a wide variety of the healing responses. The fitting function can also be scaled easily for comparison to numerical model predictions and may be useful for validating future mechanoregulatory models of coupled fracture repair and remodeling.

scholarly journals Interactions between MSCs and Immune Cells: Implications for Bone Healing

2015 ◽  
Vol 2015 ◽  
pp. 1-17 ◽  
Author(s):  
Tracy K. Kovach ◽  
Abhijit S. Dighe ◽  
Peter I. Lobo ◽  
Quanjun Cui
Keyword(s):  
Fracture Healing ◽  
Bone Healing ◽  
Immune Cells ◽  
Bone Repair ◽  
Repair Process ◽  
The United States ◽  
Fracture Repair ◽  
Cell Based Therapy

It is estimated that, of the 7.9 million fractures sustained in the United States each year, 5% to 20% result in delayed or impaired healing requiring therapeutic intervention. Following fracture injury, there is an initial inflammatory response that plays a crucial role in bone healing; however, prolonged inflammation is inhibitory for fracture repair. The precise spatial and temporal impact of immune cells and their cytokines on fracture healing remains obscure. Some cytokines are reported to be proosteogenic while others inhibit bone healing. Cell-based therapy utilizing mesenchymal stromal cells (MSCs) is an attractive option for augmenting the fracture repair process. Osteoprogenitor MSCs not only differentiate into bone, but they also exert modulatory effects on immune cells via a variety of mechanisms. In this paper, we review the current literature on bothin vitroandin vivostudies on the role of the immune system in fracture repair, the use of MSCs in the enhancement of fracture healing, and interactions between MSCs and immune cells. Insight into this paradigm can provide valuable clues in identifying cellular and noncellular targets that can potentially be modulated to enhance both natural bone healing and bone repair augmented by the exogenous addition of MSCs.

scholarly journals Zn-Containing Membranes for Guided Bone Regeneration in Dentistry

Polymers ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 1797
Author(s):  
Manuel Toledano ◽  
Marta Vallecillo-Rivas ◽  
María T. Osorio ◽  
Esther Muñoz-Soto ◽  
Manuel Toledano-Osorio ◽  
...  
Keyword(s):  
Mechanical Properties ◽  
Bone Regeneration ◽  
Bone Healing ◽  
Bone Repair ◽  
Complex Modulus ◽  
Bacterial Colonization ◽  
Guided Bone Regeneration ◽  
M2 Macrophage

Barrier membranes are employed in guided bone regeneration (GBR) to facilitate bone in-growth. A bioactive and biomimetic Zn-doped membrane with the ability to participate in bone healing and regeneration is necessary. The aim of the present study is to state the effect of doping the membranes for GBR with zinc compounds in the improvement of bone regeneration. A literature search was conducted using electronic databases, such as PubMed, MEDLINE, DIMDI, Embase, Scopus and Web of Science. A narrative exploratory review was undertaken, focusing on the antibacterial effects, physicochemical and biological properties of Zn-loaded membranes. Bioactivity, bone formation and cytotoxicity were analyzed. Microstructure and mechanical properties of these membranes were also determined. Zn-doped membranes have inhibited in vivo and in vitro bacterial colonization. Zn-alloy and Zn-doped membranes attained good biocompatibility and were found to be non-toxic to cells. The Zn-doped matrices showed feasible mechanical properties, such as flexibility, strength, complex modulus and tan delta. Zn incorporation in polymeric membranes provided the highest regenerative efficiency for bone healing in experimental animals, potentiating osteogenesis, angiogenesis, biological activity and a balanced remodeling. Zn-loaded membranes doped with SiO2 nanoparticles have performed as bioactive modulators provoking an M2 macrophage increase and are a potential biomaterial for promoting bone repair. Zn-doped membranes have promoted pro-healing phenotypes.

scholarly journals Anabolic and antiresorptive actions of locally delivered bisphosphonates for bone repair

2018 ◽  
Vol 7 (10) ◽  
pp. 548-560 ◽  
Author(s):  
I. Qayoom ◽  
D. B. Raina ◽  
A. Širka ◽  
Š. Tarasevičius ◽  
M. Tägil ◽  
...  
Keyword(s):  
Bone Resorption ◽  
Bone Regeneration ◽  
Bone Morphogenetic Proteins ◽  
Bone Repair ◽  
Biological Effects ◽  
Research Groups ◽  
Preclinical Models ◽  
Implant Fixation ◽  
Local Use

During the last decades, several research groups have used bisphosphonates for local application to counteract secondary bone resorption after bone grafting, to improve implant fixation or to control bone resorption caused by bone morphogenetic proteins (BMPs). We focused on zoledronate (a bisphosphonate) due to its greater antiresorptive potential over other bisphosphonates. Recently, it has become obvious that the carrier is of importance to modulate the concentration and elution profile of the zoledronic acid locally. Incorporating one fifth of the recommended systemic dose of zoledronate with different apatite matrices and types of bone defects has been shown to enhance bone regeneration significantly in vivo. We expect the local delivery of zoledronate to overcome the limitations and side effects associated with systemic usage; however, we need to know more about the bioavailability and the biological effects. The local use of BMP-2 and zoledronate as a combination has a proven additional effect on bone regeneration. This review focuses primarily on the local use of zoledronate alone, or in combination with bone anabolic factors, in various preclinical models mimicking different orthopaedic conditions. Cite this article: I. Qayoom, D. B. Raina, A. Širka, Š. Tarasevičius, M. Tägil, A. Kumar, L. Lidgren. Anabolic and antiresorptive actions of locally delivered bisphosphonates for bone repair: A review. Bone Joint Res 2018;7:548–560. DOI: 10.1302/2046-3758.710.BJR-2018-0015.R2.

scholarly journals Exposure to a youthful circulation rejuvenates bone repair through modulation of β-catenin

2015 ◽  
Vol 6 (1) ◽  
Author(s):  
Gurpreet S. Baht ◽  
David Silkstone ◽  
Linda Vi ◽  
Puviindran Nadesan ◽  
Yasha Amani ◽  
...  
Keyword(s):  
Bone Repair ◽  
Repair Process ◽  
Osteoblastic Differentiation ◽  
Fracture Repair ◽  
Ageing Population ◽  
Haematopoietic Cells ◽  
Age Dependent ◽  
Old Mice

Abstract The capacity for tissues to repair and regenerate diminishes with age. We sought to determine the age-dependent contribution of native mesenchymal cells and circulating factors on in vivo bone repair. Here we show that exposure to youthful circulation by heterochronic parabiosis reverses the aged fracture repair phenotype and the diminished osteoblastic differentiation capacity of old animals. This rejuvenation effect is recapitulated by engraftment of young haematopoietic cells into old animals. During rejuvenation, β-catenin signalling, a pathway important in osteoblast differentiation, is modulated in the early repair process and required for rejuvenation of the aged phenotype. Temporal reduction of β-catenin signalling during early fracture repair improves bone healing in old mice. Our data indicate that young haematopoietic cells have the capacity to rejuvenate bone repair and this is mediated at least in part through β-catenin, raising the possibility that agents that modulate β-catenin can improve the pace or quality of fracture repair in the ageing population.

BMPs as Adsorptive Proteins for Ceramic Scaffolds

2011 ◽  
Vol 493-494 ◽  
pp. 808-812
Author(s):  
K. Ito ◽  
Masaru Murata ◽  
J. Hino ◽  
Junichi Tazaki ◽  
T. Akazawa ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Bone Morphogenetic Proteins ◽  
Bone Repair ◽  
Bone Growth ◽  
Blood Compatibility ◽  
Sodium Dodecyl ◽  
Major Band ◽  
Fluid Permeability ◽  
Inducing Factors

Body fluid permeability and blood compatibility of biomaterials are especially critical properties for regenerative bone therapy [1, 2]. To have a role in bone repair, biomaterials must have the adsorptive performance of various bone growth factors. The bone-inductive property of rabbit dentin was discovered in 1967 [3]. In our previous study, we have been researching the autograft of human demineralized dentin matrices (DDM) as a clinical study [4]. DDM is an acid-insoluble collagenous material. On the other hand, hydroxyapatite (HAp) is a mineralized material. Commercially available HAp block (APACERAM-AX®,85%-porosity with micropore) has been used as the artificial biomaterial in bone therapy [5]. Bone morphogenetic proteins (BMPs) are the strong hard tissue-inducing factors [6]. In this study, we investigated the existence of BMP-2 and -7, among proteins adsorbed to DDM and HAp, using immunoblottong analyses. The DDM granules and HAp blocks (64mm3) were implanted subcutaneously in 8-week-old Wistar rats, and sacrificed at 2 days after the implantation. Explanted DDM and HAp were homogenized by the ultrasonic procedure in phosphate-buffered saline (PBS) and the adsorbed proteins were separated on a 5-20% sodium dodecyl sulphate (SDS) polyacrylamide gradient gel by electrophoresis. For Western blotting, proteins in the gel were transferred to a polyvinylidene difluoride membrane and detected by anti-BMP-2 monoclonal antibody and anti-BMP-7 monoclonal antibody. BMP-2 and BMP-7 were detected as a major band at 50 kDa among proteins collected from the in vivo implanted DDM and HAp. BMP-2 was detected the second major band at 125 kDa in HAp and both BMP-2 and BMP-7 were detected the some minor bands in DDM and HAp. The bands of BMP-2 were stronger than those of BMP-7 in all. The DDM and HAp adsorbed BMP-2 and BMP-7. These results indicate that DDM is a useful bone substitute as much as HAp, adsorbed to the bone-inducing factors, in the bone engineering field.

scholarly journals Evaluation of longitudinal time-lapsedin vivomicro-CT for monitoring fracture healing in mouse femur defect models

2019 ◽  
Author(s):  
Esther Wehrle ◽  
Duncan C Tourolle né Betts ◽  
Gisela A Kuhn ◽  
Ariane C Scheuren ◽  
Sandra Hofmann ◽  
...  
Keyword(s):  
Fracture Healing ◽  
Radiation Effects ◽  
Callus Formation ◽  
Healing Process ◽  
Fracture Repair ◽  
Micro Ct ◽  
Micro Computed Tomography ◽  
Healing Phase ◽  
Longitudinal Imaging

AbstractLongitudinalin vivomicro-computed tomography (micro-CT) is of interest to non-invasively capture the healing process of individual animals in preclinical fracture healing studies. However, it is not known whether longitudinal imaging itself has an impact on callus formation and remodeling. In this study, a scan group received weekly micro-CT measurements (week 0-6), whereas controls were only scanned post-operatively and at week 5 and 6. Registration of consecutive scans using a branching scheme (bridged vs. unbridged defect) combined with a two-threshold approach enabled assessment of localized bone turnover and mineralization kinetics relevant for monitoring callus remodeling. Weekly micro-CT application did not significantly change any of the assessed callus parameters in the defect and periosteal volumes. This was supported by histomorphometry showing only small amounts of cartilage residuals in both groups, indicating progression towards the end of the healing period. Also, immunohistochemical staining of Sclerostin, previously associated with mediating adverse radiation effects on bone, did not reveal differences between groups.The established longitudinalin vivomicro-CT-based approach allows monitoring of healing phases in mouse femur defect models without significant effects of anesthesia, handling and radiation on callus properties. Therefore, this study supports application of longitudinalin vivomicro-CT for healing-phase-specific monitoring of fracture repair in mice.

scholarly journals Growth and Morphogenetic Factors in Bone Induction: Role of Osteogenin and Related Bone Morphogenetic Proteins in Craniofacial and Periodontal Bone Repair

1992 ◽  
Vol 3 (1) ◽  
pp. 1-14 ◽  
Author(s):  
Ugo Ripamonti ◽  
A. Hari Reddi
Keyword(s):  
Bone Formation ◽  
Bone Morphogenetic Proteins ◽  
Bone Repair ◽  
Bone Development ◽  
Demineralized Bone Matrix ◽  
Bone Matrix ◽  
Prototype Model ◽  
Bone Induction ◽  
New Bone Formation

Bone has considerable potential for repair as illustrated by the phenomenon of fracture healing. Repair and regeneration of bone recapitulate the sequential stages of development. It is well known that demineralized bone matrix has the potential to induce new bone formation locally at a heterotopic site of implantation. The sequential development of bone is reminiscent of endochondral bone differentiation during bone development. The collagenous matrix-induced bone formation is a prototype model for matrix-cell interactions in vivo. The developmental cascade includes migration of progenitor cells by chemotaxis, attachment of cells through fibronectin, proliferation of mesenchymal cells, and differentiation of bone. The bone inductive protein, osteogenin, was isolated by heparin affinity chromatography. Osteogenin initiates new bone formation and is promoted by other growth factors. Recently, the genes for osteogenin and related bone morphogenetic proteins were cloned and expressed. Recombinant osteogenin is osteogenic in vivo. The future prospects for bone induction are bright, and this is an exciting frontier with applications in oral and orthopaedic surgery.

A Critical Assessment of the Clinical Efficacy and Cellular Response to Low Intensity Pulsed Ultrasound for Fracture Repair

2010 ◽  
Vol 76 ◽  
pp. 195-206
Author(s):  
Cato T. Laurencin ◽  
Yusuf Khan
Keyword(s):  
Cellular Response ◽  
Large Scale ◽  
Bone Repair ◽  
Fracture Repair ◽  
Great Promise ◽  
Pulsed Ultrasound ◽  
Invasive Treatment ◽  
In Vivo Evaluation ◽  
Low Intensity Pulsed Ultrasound ◽  
Low Intensity

Fracture repair continues to be widely investigated, both within the clinical realm and at the fundamental research level. Clinical application of low intensity pulsed ultrasound (LIPUS) has shown great promise as an effective, minimally invasive treatment for accelerating fracture repair and has warranted further investigation into the cellular manifestation of applied ultrasound. Toward this end much has been learned about the response of osteoblasts to LIPUS stimulation. In vitro and in vivo evaluation of cellular response to LIPUS have revealed an increase in proliferation, protein synthesis, collagen synthesis, membrane permeability, integrin expression, and increased cytosolic calcium, to name a few, further clarifying its utility and overall impact on cellular behavior. Considerable effects of LIPUS on the cells of musculoskeletal soft tissue have been reported as well. The growing body of research in this area suggests that LIPUS may be a powerful tool in the development of novel approaches to musculoskeletal repair and regeneration. Regenerative engineering-based approaches to musculoskeletal healing and regeneration that incorporate polymeric scaffolds and stem cells may be combined with LIPUS to move beyond bone repair to large scale multicomponent tissue repair.

Infrared Laser Light Further Improves Bone Healing When Associated with Bone Morphogenetic Proteins and Guided Bone Regeneration: An in Vivo Study in a Rodent Model

2008 ◽  
Vol 26 (2) ◽  
pp. 167-174 ◽  
Author(s):  
Antonio Luiz B. Pinheiro ◽  
Marleny E. Martinez Gerbi ◽  
Elizabeth Arruda Carneiro Ponzi ◽  
Luciana Maria Pedreira Ramalho ◽  
Aparecida M.C. Marques ◽  
...  
Keyword(s):  
Bone Regeneration ◽  
Bone Morphogenetic Proteins ◽  
Bone Healing ◽  
Laser Light ◽  
Guided Bone Regeneration ◽  
Infrared Laser ◽  
Rodent Model ◽  
In Vivo Study
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