The use of stem cells is a breakthrough in medical biotechnology which brings regenerative therapy into a new era. Over the past several decades, stem cells had been widely used as regenerative therapy and Mesenchymal Stem Cells (MSCs) had emerged as a promising therapeutic option. Currently stem cells are effective therapeutic agents againts several diseases due to their tissue protective and repair mechanisms. This therapeutic effect is largely due to the biomolecular properties including secretomes.

Autogenous bone graft is gold standard in treating bone defects, but it might have difficulty in corporation and rejection reaction. This study is to compare the effectiveness among freeze-dried xenograft, freeze-dried allograft, hydroxyapatite xenograft, and demineralized bone matrix xenograft as bone graft to fill bone defect in femoral diaphysis of white rabbit. Thirty male New Zealand white rabbits were distributed into five groups. Bone defect was filled correspondingly with xenograft freeze-dried cortical bovine, allograft freeze-dried cortical New Zealand white rabbit, xenograft hydroxyapatite bovine, and xenograft demineralized bone matrix bovine. No graft was used in control group. VEGF, osteoblast, and woven bone were higher in allograft freeze-dried cortical New Zealand white rabbit (mean 5.6625 (p<0.05)) and xenograft demineralized bone matrix bovine (mean 5.2475 (p<0.05)) with calcification of woven bone was already seen in week 2 in the latter group. There was a decrease of woven bone (mean 4.685 (p<0.05)) fibrous tissue (mean 41.07 (p<0.05)) in xenograft demineralized bone matrix bovine. The Immunoglobulin-G was elevated in control and all study groups but not significantly (p=0.07855). Bone healing process in xenograft demineralized bone matrix bovine is more effective than in xenograft hydroxyapatite bovine, allograft freeze-dried New Zealand white rabbit, xenograft freeze-dried cortical bovine, and control.

Background: Bone marrow mesenchymal stem cells (BM-MSCs) are multipotent adult stem cells and have become an important source of cells for engineering tissue repair and cell therapy. Vascular endothelial growth factor (VEGF) promotes angiogenesis and contributes fibrous integration between tendon and bone during the early postoperative stage. Both MSCs and VEGF can stimulate cell proliferation, differentiation, and matrix deposition by enhancing angiogenesis and osteogenesis of the graft in the tunnel. Hypothesis: Injection of intratunnel BM-MSCs and VEGF enhances the early healing process of a tendon graft. Study Design: Controlled laboratory study. Methods: In this controlled animal laboratory study, each of 4 groups of rabbits underwent unilateral anterior cruciate ligament (ACL) reconstruction with use of the ipsilateral semitendinosus tendon. The rabbits received intratunnel injection of BM-MSCs and VEGF with a fibrin glue seal covering the distal tunnel at the articular site. Evaluation using magnetic resonance imaging (MRI), collagen type III expression, and biomechanical analyses were performed at 3- and 6-week intervals. Results: All parameters using MRI, collagen type III expression, and biomechanical analysis of pullout strength of the graft showed that application of intratunnel BM-MSCs and VEGF enhanced tendon-to-bone healing after ACL reconstruction. Conclusion: Intratunnel injections of BM-MSCs and VEGF after ACL reconstruction enhanced graft tunnel healing. Overall, the femoral tunnel that received BM-MSCs and VEGF had better advanced healing with increased collagen type III fibers and better outcomes on MRI and biomechanical analysis. MRI is the most reliable tool for clinical use in evaluating stages of ACL healing after reconstruction, since biopsy is an invasive procedure.

Introduction: Nonunion due to a critical-sized bone defect is a complicated problem. The healing process must fulfill three mandatory elements of osteogenesis, osteoinduction, and osteoconduction. One ideal source to provide an abundant number of osteogenic cells is from the process of the culture of bone marrow stem cells which demands the availability of processing facility. Unfortunately, this sophisticated option is not always feasible in every hospital in low-income to middle-income countries. We tried to fulfill the requirement of osteogenic cells by using simple and cost-effective bone marrow aspirate. We presented two cases of critical-sized diaphyseal bone defect treated with the combination of bone marrow aspirate, cancellous bone allograft, and platelet-rich plasma (PRP). Presentation of cases: The defect sizes were five and six centimeters in humerus and tibia respectively. We applied a combination of bone marrow aspirate, cancellous bone allograft, and PRP to promote bone healing in the defect sites. Both patients have achieved the good clinical and radiological outcome. Discussion: Critical-sized bone defects require the application of tissue engineering. Aspirated bone marrow can be used as a more affordable option to provide the element of osteogenic cells in bone healing. Combined with cancellous bone allograft and PRP, they fulfill the required ingredients to promote bone regeneration. Conclusion: Bone defects remain one of the most challenging conditions to treat in orthopedic. There are many options to treat the defect but the fundamental prerequisites of cells, scaffolds and growth factors for healing have developed into the concept of tissue engineering: osteogenesis, osteoinduction, and osteoconduction. Highlights:

Tissue engineering had been believed to overcome the limitation of cartilage lesions treatment. Nowadays the studies focus on using mesenchymal stem cells in scaffold. A biodegradable porous sponge bovine cartilage scaffold is expected to have the physicobiochemical characterization to promote chondrogenic differentiation of hBM-MSCs. Scaffold from bovine cartilage was printed in 5 mm diameter sponge, categorized into nondecellularized (SBCS) and decellularized (DSBCS). Physical characteristics (pore diameter and interconnectivity) were done using a Scanning Electron Microscope (SEM). Biodegradability assessment used Phosphate Buffered Saline in 15, 30, 60 minutes, 6, 24, 48, 72 hours, and 1, 2 weeks. The swelling ratios were counted in 5, 10, 15, 30, 60, and 360 minutes. Biochemical characteristics were obtained by enzyme-linked immunosorbent assay for type II collagen, aggrecan, and Transforming Growth Factors-β (TGF-β). Data were statistically compared. hBM-MSCs were seeded on both scaffolds. Histological examination used hematoxylin-eosin taken at the 2nd and 4th weeks after seeding. There was no significant difference (p=0.473; p=0.142) on mean porosity 90.07 ± 4.64% vs. 88.93 ± 4.18% and pore diameter 111.83 ± 14.23 μm vs. 105.29 ± 11.14 μm assessment between SBCS and DSBCS groups. Scaffolds from both groups showed pore interconnectivity. DSBCS group had faster biodegradability. SBCS group sweals better. SBCS group contains type II collagen, aggrecan, and TGF-β with mean values 380.78 ± 18.63 ng/ml, 30.71 ± 4.50 ng/ml, and 130.12 ± 7.73 ng/ml, respectively, while DSBCS contained type II collagen, aggrecan, and TGF-β with mean values 64.83 ± 13.54 ng/ml, 8.41 ± 2.38 ng/ml, and 16.39 ± 4.49 ng/ml, respectively. The results were statistically different (p<0.001). Chondrocytes were found within scaffold on the 2nd and 4th weeks. Physicobiochemical characteristic of biodegradable sponge bovine cartilage scaffold promotes chondrogenic differentiation of hBM-MSCs.