Biomimetic porous scaffolds containing decellularized small intestinal submucosa and Sr2+/Fe3+ co-doped hydroxyapatite accelerate angiogenesis/osteogenesis for bone regeneration

Author(s):  
Wei Cui ◽  
Liang Yang ◽  
Ismat Ullah ◽  
Keda Yu ◽  
Zhigang Zhao ◽  
...  

Abstract The design of bone scaffolds is predominately aimed to well reproduce the natural bony environment by imitating the architecture/composition of host bone. Such biomimetic biomaterials are gaining increasing attention and acknowledged quite promising for bone tissue engineering. Herein, novel biomimetic bone scaffolds containing decellularized small intestinal submucosa matrix (SIS-ECM) and Sr2+/Fe3+ co-doped hydroxyapatite (SrFeHA) are fabricated for the first time by the sophisticated self-assembled mineralization procedure, followed by cross-linking and lyophilization post-treatments. The results indicate the constructed SIS/SrFeHA scaffolds are characterized by highly porous structures, rough microsurface and improved mechanical strength, as well as efficient releasing of bioactive Sr2+/Fe3+ and ECM components. These favorable physico-chemical properties endow SIS/SrFeHA scaffolds with an architectural/componential biomimetic bony environment which appears to be highly beneficial for inducing angiogenesis/osteogenesis both in vitro and in vivo. In particular, the cellular functionality and bioactivity of endotheliocytes/osteoblasts are significantly enhanced by SIS/SrFeHA scaffolds, and the cranial defects model further verifies the potent ability of SIS/SrFeHA to accelerate in vivo vascularization and bone regeneration following implantation. In this view these results highlight the considerable angiogenesis/osteogenesis potential of biomimetic porous SIS/SrFeHA scaffolds for inducing bone regeneration and thus may afford a new promising alternative for bone tissue engineering.

Polymers ◽  
2020 ◽  
Vol 12 (5) ◽  
pp. 1174 ◽  
Author(s):  
Shiao-Wen Tsai ◽  
Sheng-Siang Huang ◽  
Wen-Xin Yu ◽  
Yu-Wei Hsu ◽  
Fu-Yin Hsu

Collagen (COL) and hydroxyapatite (HAp) are the major components of bone, therefore, COL-HAp composites have been widely used as bone substitutes to promote bone regeneration. We have reported that HAp-CaO fibers (HANFs), which were fabricated by a sol-gel route followed by an electrospinning technique, possessed good drug-loading efficiency and limited the burst release of tetracycline. In the present study, we used HANF fragments to evaluate the effects of COL-HANF scaffolds on MG63 osteoblast-like cell behaviors. COL-HANF composite scaffolds in which the average diameter of HANFs was approximately 461 ± 186 nm were fabricated by a freeze-drying process. The alkaline phosphatase activity and the protein expression levels of OCN and BSP showed that compared with COL alone, the COL-HANF scaffold promoted the differentiation of MG63 osteoblast-like cells. In addition, the bone regeneration ability of the COL-HANF scaffold was examined by using a rabbit condylar defect model in vivo. The COL-HANF scaffold was biodegradable and promoted bone regeneration eight weeks after the operation. Hence, we concluded that the COL-HANF scaffold has potential as a bone graft for bone tissue engineering.


2018 ◽  
Vol 2018 ◽  
pp. 1-11 ◽  
Author(s):  
Weiyi Wu ◽  
Bowen Li ◽  
Yuhua Liu ◽  
Xinzhi Wang ◽  
Lin Tang

A barrier membrane (BM) is essential for guided bone regeneration (GBR) procedures. Absorbable BMs based on collagen have been widely applied clinically due to their excellent biocompatibility. The extracellular matrix (ECM) provides certain advantages that can compensate for the rapid degradation and insufficient mechanical strength of pure collagen membrane due to the porous scaffold structure. Recently, small intestinal submucosa (SIS), one of the most widely used ECM materials, has drawn much attention in bone tissue engineering. In this study, we adopted multilaminate SIS (mSIS) as a BM and evaluated its in vivo and in vitro properties. mSIS exhibited a multilaminate structure with a smooth upper surface and a significantly coarser bottom layer according to microscopic observation. Tensile strength was 13.10 ± 2.56 MPa. In in vivo experiments, we selected a rabbit mandibular defect model and subcutaneous implantation to compare osteogenesis and biodegradation properties with one of the most commonly used commercial collagen membranes. mSIS was retained for up to 3 months and demonstrated longer biodegradation time than commercial collagen membrane. Quantification of bone regeneration revealed significant differences in each group. Micro-computed tomography (micro-CT) revealed that the quantity and maturity of bones in the mSIS group were significantly higher than those in the blank control group (P < 0.05) and were similar to those in a commercial collagen membrane group (P > 0.05) at 4 and 12 weeks after surgery. Hematoxylin and eosin staining revealed large amounts of mature lamellar bone at 12 weeks in mSIS and commercial collagen membrane groups. Therefore, we conclude that mSIS has potential as a future biocompatible BM in GBR procedures.


ASAIO Journal ◽  
2002 ◽  
Vol 48 (2) ◽  
pp. 197
Author(s):  
Dai Kimura ◽  
Tatsuo Nakamura ◽  
Kenji Kaino ◽  
Yoshio Hori ◽  
Masaki Nio ◽  
...  

2017 ◽  
Vol 2017 ◽  
pp. 1-12 ◽  
Author(s):  
Jozafina Haj ◽  
Tharwat Haj Khalil ◽  
Mizied Falah ◽  
Eyal Zussman ◽  
Samer Srouji

While biologically feasible, bone repair is often inadequate, particularly in cases of large defects. The search for effective bone regeneration strategies has led to the emergence of bone tissue engineering (TE) techniques. When integrating electrospinning techniques, scaffolds featuring randomly oriented or aligned fibers, characteristic of the extracellular matrix (ECM), can be fabricated. In parallel, mesenchymal stem cells (MSCs), which are capable of both self-renewing and differentiating into numerous tissue types, have been suggested to be a suitable option for cell-based tissue engineering therapies. This work aimed to create a novel biocompatible hybrid scaffold composed of electrospun polymeric nanofibers combined with osteoconductive ceramics, loaded with human MSCs, to yield a tissue-like construct to promote in vivo bone formation. Characterization of the cell-embedded scaffolds demonstrated their resemblance to bone tissue extracellular matrix, on both micro- and nanoscales and MSC viability and integration within the electrospun nanofibers. Subcutaneous implantation of the cell-embedded scaffolds in the dorsal side of mice led to new bone, muscle, adipose, and connective tissue formation within 8 weeks. This hybrid scaffold may represent a step forward in the pursuit of advanced bone tissue engineering scaffolds.


2014 ◽  
Vol 2014 ◽  
pp. 1-10 ◽  
Author(s):  
Sahar Ansari ◽  
Marcelo O. Freire ◽  
Eun-Kyoung Pang ◽  
Alaa I. Abdelhamid ◽  
Mohammad Almohaimeed ◽  
...  

Biomaterials are widely used as scaffolds for tissue engineering. We have developed a strategy for bone tissue engineering that entails application of immobilized anti-BMP-2 monoclonal antibodies (mAbs) to capture endogenous BMPs in vivo and promote antibody-mediated osseous regeneration (AMOR). The purpose of the current study was to compare the efficacy of immobilization of a specific murine anti-BMP-2 mAb on three different types of biomaterials and to evaluate their suitability as scaffolds for AMOR. Anti-BMP-2 mAb or isotype control mAb was immobilized on titanium (Ti) microbeads, alginate hydrogel, and ACS. The treated biomaterials were surgically implanted in rat critical-sized calvarial defects. After 8 weeks,de novobone formation was assessed using micro-CT and histomorphometric analyses. Results showedde novobone regeneration with all three scaffolds with immobilized anti-BMP-2 mAb, but not isotype control mAb. Ti microbeads showed the highest volume of bone regeneration, followed by ACS. Alginate showed the lowest volume of bone. Localization of BMP-2, -4, and -7 antigens was detected on all 3 scaffolds with immobilized anti-BMP-2 mAb implanted in calvarial defects. Altogether, these data suggested a potential mechanism for bone regeneration through entrapment of endogenous BMP-2, -4, and -7 proteins leading to bone formation using different types of scaffoldsviaAMOR.


2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Jie Bai ◽  
Lijun Li ◽  
Ni Kou ◽  
Yuwen Bai ◽  
Yaoyang Zhang ◽  
...  

Abstract Background Bone tissue engineering is a new concept bringing hope for the repair of large bone defects, which remains a major clinical challenge. The formation of vascularized bone is key for bone tissue engineering. Growth of specialized blood vessels termed type H is associated with bone formation. In vivo and in vitro studies have shown that low level laser therapy (LLLT) promotes angiogenesis, fracture healing, and osteogenic differentiation of stem cells by increasing reactive oxygen species (ROS). However, whether LLLT can couple angiogenesis and osteogenesis, and the underlying mechanisms during bone formation, remains largely unknown. Methods Mouse bone marrow mesenchymal stem cells (BMSCs) combined with biphasic calcium phosphate (BCP) grafts were implanted into C57BL/6 mice to evaluate the effects of LLLT on the specialized vessel subtypes and bone regeneration in vivo. Furthermore, human BMSCs and human umbilical vein endothelial cells (HUVECs) were co-cultured in vitro. The effects of LLLT on cell proliferation, angiogenesis, and osteogenesis were assessed. Results LLLT promoted the formation of blood vessels, collagen fibers, and bone tissue and also increased CD31hiEMCNhi-expressing type H vessels in mBMSC/BCP grafts implanted in mice. LLLT significantly increased both osteogenesis and angiogenesis, as well as related gene expression (HIF-1α, VEGF, TGF-β) of grafts in vivo and of co-cultured BMSCs/HUVECs in vitro. An increase or decrease of ROS induced by H2O2 or Vitamin C, respectively, resulted in an increase or decrease of HIF-1α, and a subsequent increase and decrease of VEGF and TGF-β in the co-culture system. The ROS accumulation induced by LLLT in the co-culture system was significantly decreased when HIF-1α was inhibited with DMBPA and was followed by decreased expression of VEGF and TGF-β. Conclusions LLLT enhanced vascularized bone regeneration by coupling angiogenesis and osteogenesis. ROS/HIF-1α was necessary for these effects of LLLT. LLLT triggered a ROS-dependent increase of HIF-1α, VEGF, and TGF-β and resulted in subsequent formation of type H vessels and osteogenic differentiation of mesenchymal stem cells. As ROS also was a target of HIF-1α, there may be a positive feedback loop between ROS and HIF-1α, which further amplified HIF-1α induction via the LLLT-mediated ROS increase. This study provided new insight into the effects of LLLT on vascularization and bone regeneration in bone tissue engineering.


2010 ◽  
Vol 6 (9) ◽  
pp. 3457-3470 ◽  
Author(s):  
Tao Jiang ◽  
Syam P. Nukavarapu ◽  
Meng Deng ◽  
Ehsan Jabbarzadeh ◽  
Michelle D. Kofron ◽  
...  

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