The Clinical Therapeutic Effects and Safety of Tissue-engineered Bone

Study Overview
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Brief Summary
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The purpose of this study is to compare use of a tissue-engineered bone to use of a standard allograft bone to treat bone defect in patients. The hypothesis is that use of the tissue-engineered bone is effective and safe to treat the bone defect in patients.

Detailed Description
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Patients with the bone defect without infection and sever system diseases will be recruited. The material selected as the scaffold for this study will be a porous β-tricalcium phosphate scaffold (β-TCP) scaffold and scaffold is custom-made according to the size and shape of bone defect after three-dimensional CT scan. Human BMSCs will be obtained and cultured before operation and 3.4×106 cells in 10ml serum-free medium will be seeded onto scaffold to construct the tissue engineered bone graft and co-cultured for two weeks. The implant operation will be carried out under the general anesthesia. The tissue engineered bone graft will be implanted into the bone defect area. The bone defect area will be covered with surrounding soft tissue and muscle to close the wound. Anti-inflammatory, repercussive and analgesic drugs will be used for 1 week. Patient will be hospitalized for 1 to 2 weeks after surgery. Blood routine examination, erythrocyte sedimentation rate, immunoglobulin, autoantibodies and clinical examination will be carried out for signs of pain, swelling, immune rejection and infection. Patient will be evaluated at 3 days，3, 6, 12, 18 and 22 months after operation by radiography; Three-dimensional CT scan will be also performed at regular intervals. The function of the body will be evaluated at regular intervals.

Official Title
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The Clinical Therapeutic Effects and Safety of Tissue-engineered Bone

Conditions
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Bone Nonunion, Bone Defect

Intervention / Treatment
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* Device: allograft bone
* Device: tissue-engineered bone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: the patients with bone defect and bone nonunion caused by tumor or trauma the length of bone defect in long diaphysis is more than 4cm or more than half of the shaft diameter the size of bone defect is more than 5cmx5cm the patients are unable to use autologous bone graft or other treatments the patients request to use the treatment of tissue-engineered bone Supportive family with willingness to participate in completing questionnaires Exclusion Criteria: Patients with serious diseases such as hemorrhagic disorders, infection, tumor, contagion and so on. Patients who are pregnant Patients with serious abnormal cardiopulmonary function Patients disagree to use the tissue-engineered bone Patients are older than 60 years Patients who are regarded to be unqualified by investigator

Ages Eligible for Study
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Minimum Age: 1 Year
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: allograft bone<br>traditional allograft bone | Device: allograft bone<br>* Use of the allograft bone to treat the bone defect in patients<br>|
| Experimental: tissue-engineered bone<br>tissue-engineered bone | Device: tissue-engineered bone<br>* Use of the tissue-engineered bone to treat the bone defect in patients<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The scores of bone healing | The scores of bone healing are divided into three kinds: nonhealing: 0; delayed healing: 1; normal healing: 2. The average score of tissue-engineered bone is compared with the score of control group using allograft bone to verify the clinical efficacy of tissue-engineered bone. | within 48 weeks after surgical treatment of bone dect | 
| the adverse event incidence using tissue-engineered bone and allograft bone | the adverse event incidence of tissue-engineered bone is compared with the adverse event incidence of allograft bone to verify the safety of tissue-engineered bone. | within 24 weeks after surgical treatment of bone dect | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The scores of blood routine test | The scores of blood routine test after operation are divided into three kinds: severely abnormal：0；abnormal：1；normal：2. The average score of tissue-engineered bone is compared with the score of control group using allograft bone to verify the clinical efficacy of tissue-engineered bone. | within 48 weeks after surgical treatment of bone dect | 
| The scores of erythrocyte sedimentation rate(ESR) | The scores of erythrocyte sedimentation rate (ESR) after operation are divided into three kinds: severely abnormal：0；abnormal：1；normal：2. The average score of tissue-engineered bone is compared with the score of control group using allograft bone to verify the clinical efficacy of tissue-engineered bone. | within 48 weeks after surgical treatment of bone dect | 
| The scores of C-reactive protein | The scores of C-reaction protein after operation are divided into three kinds: severely abnormal：0；abnormal：1；normal：2. The average score of tissue-engineered bone is compared with the score of control group using allograft bone to verify the clinical efficacy of tissue-engineered bone. | within 48 weeks after surgical treatment of bone dect | 
| The scores of the ratio of complement C3 to complement C4 | The scores of ratio of complement C3 to C4 after operation are divided into three kinds: severely abnormal：0；abnormal：1；normal：2. The average score of tissue-engineered bone is compared with the score of control group using allograft bone to verify the clinical efficacy of tissue-engineered bone. | within 48 weeks after surgical treatment of bone dect | 
| The scores of immunoglobulin assay | The scores of immunoglobulin assay (IgG, IgA and IgM) after operation are divided into three kinds: severely abnormal：0；abnormal：1；normal：2. The average score of tissue-engineered bone is compared with the score of control group using allograft bone to verify the clinical efficacy of tissue-engineered bone. | within 48 weeks after surgical treatment of bone dect | 
| The scores of duration of hospital stay | The scores of duration of hospital stay are divided into four kinds: longer than one months: 0; longer than two weeks:1; longer than one week:2; less than one week:3. The average score of tissue-engineered bone is compared with the score of control group using allograft bone to verify the clinical efficacy of tissue-engineered bone. | within 48 weeks after surgical treatment of bone dect | 
| the scores of time of weight loading after operation | The scores of time of weight loading after operation are divided into three kinds: longer than six months: 0; longer than three months:1; less than three months:2. The average score of tissue-engineered bone is compared with the score of control group using allograft bone to verify the clinical efficacy of tissue-engineered bone. | within 48 weeks after surgical treatment of bone dect | 
| The scores of tumorigenesis | The scores of tumorigenesis after operation are divided into three kinds: severely abnormal：0；abnormal：1；normal：2. The average score of tissue-engineered bone is compared with the score of control group using allograft bone to verify the clinical efficacy of tissue-engineered bone. | within 48 weeks after surgical treatment of bone dect | 
| The scores of treatment course | The scores of treatment course are divided into three kinds: long：0；general ：1；short：2. The average score of tissue-engineered bone is compared with the score of control group using allograft bone to verify the clinical efficacy of tissue-engineered bone. | within 48 weeks after surgical treatment of bone dect | 
| The scores of number of operations | The scores of number of operations are divided into four kinds: above three times：0； three times：1；two times：2；one time：3. The average score of tissue-engineered bone is compared with the score of control group using allograft bone to verify the clinical efficacy of tissue-engineered bone. | within 48 weeks after surgical treatment of bone dect | 
| The scores of pain | The scores of pain after operation are divided into four kinds: severe:0;moderate:1;slight:2; none:3. The average score of tissue-engineered bone is compared with the score of control group using allograft bone to verify the clinical efficacy of tissue-engineered bone. | within 48 weeks after surgical treatment of bone dect | 
| The scores of wound healing of soft tissue | The scores of wound healing are divided into four kinds: infection: 0; no healing: 1; delayed healing: 2; normal healing: 3. The average score of tissue-engineered bone is compared with the score of control group using allograft bone to verify the clinical efficacy of tissue-engineered bone. | within 48 weeks after surgical treatment of bone dect |