scholarly journals Engineering Immunomodulatory and Osteoinductive Implant Surfaces via Mussel Adhesion-Mediated Ion Coordination and Molecular Clicking

Author(s):  
Tao Wang ◽  
Jiaxiang Bai ◽  
Min Lu ◽  
Chenglong Huang ◽  
Dechun Geng ◽  
...  

Abstract Immune action and new tissue formation are two distinct but overlapping stages involved in tissue regeneration process. However, current biomaterial design is trapped into a one-sided consideration with either focusing on the regulation of immune response or paying attention to induction of new tissue formation. Bone implants also face the same problem. In this work, we designed a dual-effect bone implant with immunomodulatory activity with direct osteogenicity by a mussel adhesion-mediated ion coordination and molecular clicking strategy. The mussel-inspired chemistry for surface adhesion, bioclickable way for molecular conjugation, and coordination means for ion loading led to an immunoactive Zn2+ ion and osteoinductive BMP-2 peptide co-modified coating on bone implants. We demonstrated that the dual-effect coating could better improve cytocompatibility and promote the polarization of macrophages to M2 phenotype in vitro and in vivo. Moreover, the Zn2+ ion and BMP-2 peptide co-modified bone implants showed optimal osteogenicity and osseointegration, thus improving implant stability in vivo. We anticipate this study would provide new ideas and solutions for engineering implants with immunoactivity and tissue inductivity to precisely adapt tissue regeneration microenvironment.

2012 ◽  
Vol 529-530 ◽  
pp. 475-479 ◽  
Author(s):  
Ruggero Bosco ◽  
Michele Iafisco ◽  
Jeroen van den Beucken ◽  
Sander C.G. Leeuwenburgh ◽  
John A. Jansen

The possibility to develop a bone implant with bioactive aspects and in situ drug-delivery properties, in order to provide local treatment in vivo, is a big challenge. Where conventional surface modifications for bone implants focused on the deposition of ceramic (mostly calcium phosphate, CaP) coatings, current surface engineering approaches attempt to incorporate active features to render bone implant surfaces capable to direct biological performance. Biomimetic apatite nanocrystals (nAp) represent, among the CaPs, an elective material for bone applications and their surface functionalization with drugs allows them to act as a drug-delivery vehicle. Since load-bearing bone implants are increasingly used in patients with compromised health conditions, surface engineering is important to warrant the performance of these implants under such conditions. In view of this, bisphosphonates (BPs) represent a treatment modality for a variety of disorders of bone metabolism associated to bone loss, including Paget's bone disease, osteoporosis, fibrous dysplasia and bone metastases. In this work, we have synthesized and characterized bioinspired nAp and evaluated their functionalization with alendronate. In vitro tests will be used to evaluate the efficacy of the functionalized compound to impede the formation of osteoclasts and to show that alendronate-functionalized nAp can significantly reduce osteoclasteogenesis. Finally, alendronate-functionalized nAp (FnAp) has been deposited on titanium implants via the electrospray deposition technique in order to develop inorganic-organic coatings for bone implants with improved functionality.


2022 ◽  
Vol 13 (1) ◽  
Author(s):  
Tao Wang ◽  
Jiaxiang Bai ◽  
Min Lu ◽  
Chenglong Huang ◽  
Dechun Geng ◽  
...  

AbstractImmune response and new tissue formation are important aspects of tissue repair. However, only a single aspect is generally considered in previous biomedical interventions, and the synergistic effect is unclear. Here, a dual-effect coating with immobilized immunomodulatory metal ions (e.g., Zn2+) and osteoinductive growth factors (e.g., BMP-2 peptide) is designed via mussel adhesion-mediated ion coordination and molecular clicking strategy. Compared to the bare TiO2 group, Zn2+ can increase M2 macrophage recruitment by up to 92.5% in vivo and upregulate the expression of M2 cytokine IL-10 by 84.5%; while the dual-effect of Zn2+ and BMP-2 peptide can increase M2 macrophages recruitment by up to 124.7% in vivo and upregulate the expression of M2 cytokine IL-10 by 171%. These benefits eventually significantly enhance bone-implant mechanical fixation (203.3 N) and new bone ingrowth (82.1%) compared to the bare TiO2 (98.6 N and 45.1%, respectively). Taken together, the dual-effect coating can be utilized to synergistically modulate the osteoimmune microenvironment at the bone-implant interface, enhancing bone regeneration for successful implantation.


2021 ◽  
Vol 22 (22) ◽  
pp. 12560
Author(s):  
Su Hee Kim ◽  
Donghak Kim ◽  
Misun Cha ◽  
Soo Hyun Kim ◽  
Youngmee Jung

A dome-shaped elastic poly (l-lactide-co-caprolactone) (PLCL) scaffold with a channel and pore structure was fabricated by a combinative method of 3D printing technology and the gel pressing method (13 mm in diameter and 6.5 mm in thickness) for patient-specific regeneration. The PLCL scaffold was combined with adipose decellularized extracellular matrix (adECM) and heart decellularized extracellular matrix (hdECM) hydrogels and human adipose-derived stem cells (hADSCs) to promote adipogenesis and angiogenesis. These scaffolds had mechanical properties similar to those of native adipose tissue for improved tissue regeneration. The results of the in vitro real-time PCR showed that the dECM hydrogel mixture induces adipogenesis. In addition, the in vivo study at 12 weeks demonstrated that the tissue-engineered PLCL scaffolds containing the hydrogel mixture (hdECM/adECM (80:20)) and hADSCs promoted angiogenesis and adipose tissue formation, and suppressed apoptosis. Therefore, we expect that our constructs will be clinically applicable as material for the regeneration of patient-specific large-sized adipose tissue.


2020 ◽  
Vol 48 (3) ◽  
pp. 755-764
Author(s):  
Benjamin B. Rothrauff ◽  
Rocky S. Tuan

Bone possesses an intrinsic regenerative capacity, which can be compromised by aging, disease, trauma, and iatrogenesis (e.g. tumor resection, pharmacological). At present, autografts and allografts are the principal biological treatments available to replace large bone segments, but both entail several limitations that reduce wider use and consistent success. The use of decellularized extracellular matrices (ECM), often derived from xenogeneic sources, has been shown to favorably influence the immune response to injury and promote site-appropriate tissue regeneration. Decellularized bone ECM (dbECM), utilized in several forms — whole organ, particles, hydrogels — has shown promise in both in vitro and in vivo animal studies to promote osteogenic differentiation of stem/progenitor cells and enhance bone regeneration. However, dbECM has yet to be investigated in clinical studies, which are needed to determine the relative efficacy of this emerging biomaterial as compared with established treatments. This mini-review highlights the recent exploration of dbECM as a biomaterial for skeletal tissue engineering and considers modifications on its future use to more consistently promote bone regeneration.


2021 ◽  
Vol 19 ◽  
pp. 228080002110068
Author(s):  
Hsien-Te Chen ◽  
Hsin-I Lin ◽  
Chi-Jen Chung ◽  
Chih-Hsin Tang ◽  
Ju-Liang He

Here, we present a bone implant system of phase-oriented titanium dioxide (TiO2) fabricated by the micro-arc oxidation method (MAO) on β-Ti to facilitate improved osseointegration. This (101) rutile-phase-dominant MAO TiO2 (R-TiO2) is biocompatible due to its high surface roughness, bone-mimetic structure, and preferential crystalline orientation. Furthermore, (101) R-TiO2 possesses active and abundant hydroxyl groups that play a significant role in enhancing hydroxyapatite formation and cell adhesion and promote cell activity leading to osseointegration. The implants had been elicited their favorable cellular behavior in vitro in the previous publications; in addition, they exhibit excellent shear strength and promote bone–implant contact, osteogenesis, and tissue formation in vivo. Hence, it can be concluded that this MAO R-TiO2 bone implant system provides a favorable active surface for efficient osseointegration and is suitable for clinical applications.


Cancers ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 855
Author(s):  
Paola Serrano Martinez ◽  
Lorena Giuranno ◽  
Marc Vooijs ◽  
Robert P. Coppes

Radiotherapy is involved in the treatment of many cancers, but damage induced to the surrounding normal tissue is often inevitable. Evidence suggests that the maintenance of homeostasis and regeneration of the normal tissue is driven by specific adult tissue stem/progenitor cells. These tasks involve the input from several signaling pathways. Irradiation also targets these stem/progenitor cells, triggering a cellular response aimed at achieving tissue regeneration. Here we discuss the currently used in vitro and in vivo models and the involved specific tissue stem/progenitor cell signaling pathways to study the response to irradiation. The combination of the use of complex in vitro models that offer high in vivo resemblance and lineage tracing models, which address organ complexity constitute potential tools for the study of the stem/progenitor cellular response post-irradiation. The Notch, Wnt, Hippo, Hedgehog, and autophagy signaling pathways have been found as crucial for driving stem/progenitor radiation-induced tissue regeneration. We review how these signaling pathways drive the response of solid tissue-specific stem/progenitor cells to radiotherapy and the used models to address this.


Nutrients ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1860
Author(s):  
Patricia Diez-Echave ◽  
Izaskun Martín-Cabrejas ◽  
José Garrido-Mesa ◽  
Susana Langa ◽  
Teresa Vezza ◽  
...  

Limosilactobacillus reuteri INIA P572 is a strain able to produce the antimicrobial compound reuterin in dairy products, exhibiting a protective effect against some food-borne pathogens. In this study, we investigated some probiotic properties of this strain such as resistance to gastrointestinal passage or to colonic conditions, reuterin production in a colonic environment, and immunomodulatory activity, using different in vitro and in vivo models. The results showed a high resistance of this strain to gastrointestinal conditions, as well as capacity to grow and produce reuterin in a human colonic model. Although the in vitro assays using the RAW 264.7 macrophage cell line did not demonstrate direct immunomodulatory properties, the in vivo assays using a Dextran Sulphate Sodium (DSS)-induced colitic mice model showed clear immunomodulatory and protective effects of this strain.


2017 ◽  
Vol 49 (1) ◽  
pp. e26
Author(s):  
A. Cappon ◽  
G. Villano ◽  
S. Quarta ◽  
A. Biasiolo ◽  
C. Turato ◽  
...  

2019 ◽  
Vol 8 (12) ◽  
pp. 2091 ◽  
Author(s):  
Stuart B. Goodman ◽  
Jiri Gallo

Clinical studies, as well as in vitro and in vivo experiments have demonstrated that byproducts from joint replacements induce an inflammatory reaction that can result in periprosthetic osteolysis (PPOL) and aseptic loosening (AL). Particle-stimulated macrophages and other cells release cytokines, chemokines, and other pro-inflammatory substances that perpetuate chronic inflammation, induce osteoclastic bone resorption and suppress bone formation. Differentiation, maturation, activation, and survival of osteoclasts at the bone–implant interface are under the control of the receptor activator of nuclear factor kappa-Β ligand (RANKL)-dependent pathways, and the transcription factors like nuclear factor κB (NF-κB) and activator protein-1 (AP-1). Mechanical factors such as prosthetic micromotion and oscillations in fluid pressures also contribute to PPOL. The treatment for progressive PPOL is only surgical. In order to mitigate ongoing loss of host bone, a number of non-operative approaches have been proposed. However, except for the use of bisphosphonates in selected cases, none are evidence based. To date, the most successful and effective approach to preventing PPOL is usage of wear-resistant bearing couples in combination with advanced implant designs, reducing the load of metallic and polymer particles. These innovations have significantly decreased the revision rate due to AL and PPOL in the last decade.


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