Testing Tissue Engineering Techniques On Goats With Coral Hydroxyapatite, CHAP And Bone Marrow Stromal Stem Cells, BMSCs

In me recent studying of using different types of tissue engineering ideas for bone defects ossification, I found two studies which I felt was worth really looking into to see how well two types of materials, the Coral Hydroxyapatite, CHAP and Bone Marrow Stromal Stem Cells, BMSCs will work in the healing of non-unions of bones. The previous post showed that the types of tissue engineered bone marrow stroma cells may not be that effective in being used for osteogeneis and/or bone healing.

Analysis & Interpretation

We see that these two studies are very similar to the article/study we looked at in the previous post since the same authors wrote these articles too. All of them are looking at the effectiveness of the coral hydroxyapatite (CHAP) and the bone marrow stroma stem cells (BMSCs).

From the 1st study, we see the same thing where only the CHAP and the BMSCs are being looked at for their effectiveness on the same type of bone defect, 2 cms. However in this study it seems that the researchers using the same type of bone formation measuring equipment noted that that the tissue engineering and the CHAP were effective after a few months. They conclude with “Tissue-engineered bone is capable of total repair of large bone defect in goats by forming normal functional new bones. CHAP can be eventually degraded completely and become the component of the newly generated bones.

From the 2nd study, I have only been able to get the abstract but still have been away to take away a few important parts. This study was similar but had a little more information which we can use for later research. the test animal were goats again. This time a 2.5 cm long defect was made to the middle of the right femur of the goats. What I would learn from this arbstract and study is that there should be two parts to the bone defect implant. If we imagine the bone defect being around 1 inch long, we realize we can’t just squeeze from type of stem cell into the bone layer and hope it will heal. There needs to be some type of scaffold or spongelike, porous, solid matrix material to hold the stem cells.

This is a lesson from tissue engineering research. For any type of implantation from grown/cultured cells, there has to be usually two parts to the implant.

1. The stem cells – For this study, we are looking at bone marrow stroma cells –

2. The medium for it to go into, or for this study, the coral hydroxyapatite – This is the matrix which the BMSCs are added into. The cells go into the empty cavities and line the inner walls of the matrix, and then the cells can interact with the cells of the surrounding natural tissues once the stem cell-scaffold is finally implanted.

The goats were actually broken up into two groups, the experimental and the control The control did have their femur also drilled with the same size of defect and had some other coral derivative added into the medium. The results showed that the MSCSs which are used to create bone with the CHAP matrix as a carrier did result in the bone healing almost properly after 4 months. The results showed that the two compounds worked well and the bones after healing was tested and had similar bone strength and rigidity as a bone which had not been drilled.

Implications For Height Increase

I think at this point it is clear that if we choose the distraction of bone idea, we would need to use the standard stem cell embedded into scaffold idea. Let’s remember that the coral hydroxyapatite is really just the non-organic, non-living mineral based element that makes the hard structure in our bone. Our bones have living and non living elements. The chondrocytes, stem cells, and such are living elements, cells. The nonliving elements are the proteins, the chemical compounds and elements, and the inorganic mineral stuff that make the bone. Bones get their hardness and have the matrix of the bone formed from the calcium derived hydroxyapatite. The researchers did note that this compound is great as a carrier/substrate because it can easily be resorbed by the bone system and leave almost a perfectly natural beone segment.

Let’s note that the stem cells which are supposed to be doing the real bone formation is the bone marrow stroma cells (BMSCs). The CHAP is used because it is so similar to the minerals already found in bone. The bonding is good and the human body doesn’t seem to reject it. This post shows us that the CHAP may be a very good candidate for a carrier/matrix element to be used in any proposed height increasing invasive implantation ideas.


From PubMed study 1 Long-term observation of large weight-bearing bone defect in goats repaired with tissue engineering technique

Nan Fang Yi Ke Da Xue Xue Bao. 2006 Jun;26(6):770-3. [Article in Chinese]  –  Chen B, Pei GX, Wang K, Tang GH.

Source – Department of Orthopedics and Traumatology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.

Abstract

OBJECTIVE:

To observe the long-term effect of tissue engineering-based repair of large weight-bearing bone defect in goats, and the final outcome of the scaffold material coral hydroxyapatite (CHAP) in vivo.

METHODS:

Fifteen Chinese goats were subjected to operations to induce a 2-cm left tibial diaphyseal defect, which was filled subsequently with CHAP and bone marrow stromal stem cells (BMSCs). The repaired defects were evaluated by ECT, X-ray and histology in the early stage and at 6, 12, 18, and 24 months postoperatively.

RESULTS:

ECT showed good bone regeneration and revascularization within 2 months postoperatively. X-ray and histology displayed eccentric and gradual bone regeneration in the early stage, and the tissue-engineered bone graft was firmly healed with the goat tibia. X-ray and histological examination at 6, 12, 18, 24 months postoperatively revealed moulding of the new bones and medullary cavity recanalization, and the structure of CHAP disappeared and gradually integrated into the new bones.

CONCLUSION:

Tissue-engineered bone is capable of total repair of large bone defect in goats by forming normal functional new bones. CHAP can be eventually degraded completely and become the component of the newly generated bones.

PMID:   16793597      [PubMed – indexed for MEDLINE]     Free full text 

From PubMed study 2 link Tissue-engineered bone repair of goat-femur defects with osteogenically induced bone marrow stromal cells.

Tissue Eng. 2006 Mar;12(3):423-33. –  Zhu L, Liu W, Cui L, Cao Y.

Source – Department of Plastic and Reconstructive Surgery, Shanghai Ninth People’s Hospital, Shanghai Tissue Engineering Center, Shanghai Second Medical University, Shanghai, China.

Abstract

Tissue engineering can generate bone tissue and has been shown to provide a better means of repairing weight-bearing bone defect. Previous studies, however, have heretofore been limited to the use of nonosteogenically induced bone marrow stromal cells (BMSCs) or the application of slow-degradation scaffolds. In this study, weight-bearing bone was engineered using osteogenically induced BMSCs. In addition, coral was used as a scaffold material, due to its proper degradation rate for the engineering and repair of a goat femur defect. A 25 mm long defect was created at the middle of the right femur in each of 10 goats. The rates of defect repair were compared in an experimental group of ten goats receiving implants containing osteogenically induced BMSCs and in the control group of goats (n = 10) receiving just coral cylinders. In the experimental group, bony union was observed by radiographic and gross view at 4 months, and engineered bone was further remodeled into newly formed cortexed bone at 8 months. There was increased gray density of radiographic rays in the repaired area, which was significantly different (p < 0.05) from that of the control group. H&E staining demonstrated that trabecular bone was formed at 4 months. Moreover, irregular osteon was observed at 8 months. Most importantly, the tissue-engineered bone segment revealed a similarity to the left-side normal femur in terms of bend load strength and bend rigidity, showing no significant difference (p > 0.05). In contrast, the coral cylinders of the control group showed no bone formation. Furthermore, almost complete resorption of the carrier had occurred, being evident at 2 months in the control group. H&E staining demonstrated that a small amount of residual coral particle was surrounded by fibrous tissue at 4 months whereas the residues disappeared at 8 months. Based on these results, we conclude that engineered bone from osteogenically induced BMSCs and coral can ideally heal critical-sized segmental bone defects in the weight-bearing area of goats.

PMID:   16579676     [PubMed – indexed for MEDLINE]

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