In vivo</italic> bone regeneration with injectable chitosan/hydroxyapatite/collagen composites and mesenchymal stem cells

doi:10.1007/s11706-011-0142-4

Front Mater Sci

2011, Vol. 5

Issue (3) : 301-310 https://doi.org/10.1007/s11706-011-0142-4

RESEARCH ARTICLE

In vivo bone regeneration with injectable chitosan/hydroxyapatite/collagen composites and mesenchymal stem cells

Zhi HUANG¹, Yan CHEN², Qing-Ling FENG¹(

), Wei ZHAO³, Bo YU⁴(

), Jing TIAN⁴, Song-Jian LI⁴, Bo-Miao LIN⁵

1. Department of Materials Science and Engineering, Tsinghua University, Beijing 100084, China; 2. Department of Ultrasonic Diagnosis, Zhujiang Hospital of Southern Medical University, Guangzhou 510282, China; 3. Institute of High Energy Physics, Chinese Academy of Sciences, Beijing 100049, China; 4. Department of Orthopedics, Zhujiang Hospital of Southern Medical University, Guangzhou 510282, China; 5. Department of Radiology, Zhujiang Hospital of Southern Medical University, Guangzhou 510282, China

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Abstract

For reconstruction of irregular bone defects, injectable biomaterials are more appropriate than the preformed biomaterials. We herein develop a biomimetic in situ-forming composite consisting of chitosan (CS) and mineralized collagen fibrils (nHAC), which has a complex hierarchical structure similar to natural bone. The CS/nHAC composites with or without mesenchymal stem cells (MSCs) are injected into cancellous bone defects at the distal end of rabbit femurs. Defects are assessed by radiographic, histological diagnosis and Raman microscopy until 12 weeks. The results show that MSCs improve the biocompatibility of CS/nHAC composites and enhance new bone formation in vivo at 12 weeks. It can be concluded that the injectable CS/nHAC composites combined with MSCs may be a novel method for reconstruction of irregular bone defects.

Keywords mineralized collagen fibrils in situ-forming injectable mesenchymal stem cells tissue engineered bone

Corresponding Author(s): FENG Qing-Ling,Email:biomater@mail.tsinghua.edu.cn (Q.L.F.); YU Bo,Email:gzyubo@gmail.com (B.Y.)

Issue Date: 05 September 2011

Cite this article:

Zhi HUANG,Yan CHEN,Qing-Ling FENG, et al. In vivo bone regeneration with injectable chitosan/hydroxyapatite/collagen composites and mesenchymal stem cells[J]. Front Mater Sci, 2011, 5(3): 301-310.

URL:

https://academic.hep.com.cn/foms/EN/10.1007/s11706-011-0142-4
https://academic.hep.com.cn/foms/EN/Y2011/V5/I3/301

Fig.1 Intraoperative view of a cylindrical 7 mm × 10 mm osseous critical-sized defect at the distal femoral end of the rabbit.

Fig.2 High resolution μCT images in rabbit distal femur taken 12 weeks after implantation. The untreated defect, the formation of new bone remains restricted to the edge of the cavity and the largest part of the centre of the cavity remains free of bone. The chitosan treated defect, trabecula from the surrounding bone is growing towards the centre of the cavity, but the cavity is still visible. The CS/nHAC treated defect, most of the cavity is occupied by new bone, but the central part of the cavity is still free of bone. The CS/nHAC/MSC treated defect, trabecula from the surrounding bone is growing towards the centre of the cavity, and the central part of the cavity is occupied by new bone. (C: cavity; T: trabecula; N: new bone)

Fig.3 Bone-mineral density measured in the implanted area, with Hounsfield units (HU) at 4, 8 and 12 weeks for each group ( = 3). (a - untreated group; b - CS group; c - CS/nHAC group; d - CS/nHAC/MSC group; * - <0.05)

Fig.4 Light microscopy photographs of the histology sections taken 12 weeks after implantation for CS group: HE, 50×; HE, 200×; Masson, 50×; Masson, 200×. (BM: bone marrow; CS: chitosan; FC: fibrotic capsule)

Fig.5 Light microscopy photographs of the histology sections taken 12 weeks after implantation for CS/nHAC group: HE, 40×; HE, 200×; Masson, 40×; Masson, 400×. (NB: newly formed bone; BM: bone marrow; CS: chitosan; HA: nHAC)

Fig.6 Light microscopy photographs of the histology sections taken 12 weeks after implantation for the CS/nHAC/MSC group: HE, 20×; HE, 400×; Masson, 20×; Masson, 400×. (NB: newly formed bone; BM: bone marrow; CB: collagen bundles)

Fig.7 Raman spectra for the native bone and newly formed bone in the CS/nHAC/MSC group.

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