Search

We have previously reported that serum albumin-coated bone allograft (BoneAlbumin, BA) is an effective bone substitute. It improves bone regeneration at the patellar and tibial donor sites six months after harvesting bone-patellar tendon-bone (BPTB) autografts for primary anterior cruciate ligament reconstruction (ACLR). In the present study, we examined these donor sites seven years after implantation. The study group (N = 10) received BA-enhanced autologous cancellous bone at the tibial and BA alone at the patellar site. The control group (N = 16) received autologous cancellous bone at the tibial and blood clot at the patellar site. We evaluated subcortical density, cortical thickness, and bone defect volume via CT scans. At the patellar site, subcortical density was significantly higher in the BA group at both time points. There was no significant difference in cortical thickness between the two groups at either donor site. The control group’s bone defect significantly improved and reached the BA group’s values at both sites by year seven. Meanwhile, the bone defects in the BA group did not change significantly and were comparable to the six-month measurements. No complications were observed. There are two limitations in this study: The number of patients recruited is small, and the randomization of the patients could have improved the quality of the study as the control group patients were older compared to the study group patients. Our 7-year results seem to demonstrate that BA is a safe and effective bone substitute that supports faster regeneration of donor sites and results in good-quality bone tissue at the time of ACLR with BPTB autografts. However, studies with a larger number of patients are required to definitively confirm the preliminary results of our study.

Serum albumin‐coated bone allografts (BoneAlbumin) have successfully supported bone regeneration in various experimental models by activating endogenous progenitors. However, the effect of tissue aging, linked to declining stem cell function, has yet to be explicitly examined within the context of BoneAlbumin's regenerative capacity. Stem cell function was tested with an in vitro attachment assay, which showed that albumin coating increases stem cell attachment on demineralized bone surfaces in an aging cell population. Bone regeneration was investigated in vivo by creating critical size bone defects on the parietal bones of aging female rats. Demineralized bone matrices with and without serum albumin coating were used to fill the defects. Bone regeneration was determined by measuring the density and the size of the remaining bone defect with computed tomography (CT). Microcomputed tomography (MicroCT) and mechanical testing were performed on the parietal bone explants. In vivo CT and ex vivo microCT measurements showed better regeneration with albumin‐coated grafts. Additionally, the albumin‐coated group showed a twofold increase in peak fracture force compared with uncoated allografts. In the present study, serum albumin‐coated demineralized bone matrices successfully supported faster and functionally superior bone regeneration in aging rats. Because stem cell function, a key contributor of bone remodelling, decreases with age and serum albumin is an effective activator of endogenous progenitor cells, this method could be an effective and safe adjuvant in bone regeneration of aging adult and osteo‐compromised populations.

Blood serum fractions are hotly debated adjuvants in bone replacement therapies. In the present experiment, we coated demineralized bone matrices (DBM) with serum albumin and investigated stem cell attachment in vitro and bone formation in a rat calvaria defect model. In the in vitro experiments, we observed that significantly more cells adhere to the serum albumin coated DBMs at every time point. In vivo bone formation with albumin coated and uncoated DBM was monitored biweekly by computed tomography until 11 weeks postoperatively while empty defects served as controls. By the seventh week, the bone defect in the albumin group was almost completely closed (remaining defect 3.0 ± 2.3%), while uncoated DBM and unfilled control groups still had significant defects (uncoated: 40.2 ± 9.1%, control: 52.4 ± 8.9%). Higher density values were also observed in the albumin coated DBM group. In addition, the serum albumin enhanced group showed significantly higher volume of newly formed bone in the microCT analysis and produced significantly higher breaking force and stiffness compared to the uncoated grafts (peak breaking force: uncoated: 15.7 ± 4 N, albumin 46.1 ± 11 N). In conclusion, this investigation shows that implanting serum albumin coated DBM significantly reduces healing period in nonhealing defects and results in mechanically stronger bone. These results also support the idea that serum albumin coating provides a convenient milieu for stem cell function, and a much improved bone grafting success can be achieved without the use of exogenous stem cells.

Albumin is a major plasma protein that has become ubiquitous in regenerative medicine research. As such, many studies have examined its structure and advantageous properties. However, a systematic and comprehensive understanding of albumin's role, capabilities and therapeutic potential still eludes the field. In the present work, we review how albumin is applied in tissue engineering, including cell culture and storage, in vitro fertilization and transplantation. Furthermore, we discuss how albumin's physiological role extends beyond a carrier for metal ions, fatty acids, pharmacons and growth factors. Albumin acts as a bacteriostatic coating that simultaneously promotes attachment and proliferation of eukaryotic cells. These properties with the combination of free radical scavenging, neutrophil activation and as a buffer molecule already make the albumin protein beneficial in healing processes supporting functional tissue remodeling. Nevertheless, recent data revealed that albumin can be synthesized by osteoblasts and its local concentration is raised after bone trauma. Interestingly, by increasing the local albumin concentration in vivo, faster bone healing is achieved, possibly because albumin recruits endogenous stem cells and promotes the growth of new bone. These data also suggest an active role of albumin, even though a specific receptor has not yet been identified. Together, this discussion sheds light on why the extravascular use of the albumin molecule is in the scope of scientific investigations and why it should be considered as a local therapeutic agent in regenerative medicine. © 2016 BioFactors, 43(3):315-330, 2017.

Blood serum fractions are hotly debated adjuvants in bone replacement therapies. In the present experiment, we coated demineralized bone matrices (DBM) with serum albumin and investigated stem cell attachment in vitro and bone formation in a rat calvaria defect model. In the in vitro experiments, we observed that significantly more cells adhere to the serum albumin coated DBMs at every time point. In vivo bone formation with albumin coated and uncoated DBM was monitored biweekly by computed tomography until 11 weeks postoperatively while empty defects served as controls. By the seventh week, the bone defect in the albumin group was almost completely closed (remaining defect 3.0 ± 2.3%), while uncoated DBM and unfilled control groups still had significant defects (uncoated: 40.2 ± 9.1%, control: 52.4 ± 8.9%). Higher density values were also observed in the albumin coated DBM group. In addition, the serum albumin enhanced group showed significantly higher volume of newly formed bone in the microCT analysis and produced significantly higher breaking force and stiffness compared to the uncoated grafts (peak breaking force: uncoated: 15.7 ± 4 N, albumin 46.1 ± 11 N). In conclusion, this investigation shows that implanting serum albumin coated DBM significantly reduces healing period in nonhealing defects and results in mechanically stronger bone. These results also support the idea that serum albumin coating provides a convenient milieu for stem cell function, and a much improved bone grafting success can be achieved without the use of exogenous stem cells.

Cell therapy holds the promise for a novel modality in the surgical toolkit; however, delivery of cells into damaged soft tissues constitutes a challenge. The authors hypothesized that growing stem cells on the surface of absorbable sutures in vitro and then implanting them via stitching would be a suitable delivery route for cell therapy. Fibronectin, poly-L-lysine, and albumin coatings were used to increase attachment of human and rat bone-marrow-derived mesenchymal stem cells (BMSC) to polyfilament absorbable sutures in vitro. Fluorescence microscopy was performed to localize the cells on the suture. After 48 hours of incubation, the albumin-coated sutures had the highest cell number, and after 168 hours cell number reached confluency. In the in vivo experiments, a 10-mm incision was made on the triceps surae muscle of male Wistar rats and rat BMSC coated sutures were placed into the muscle. Two days after the implantation, cells were seen on the surface of the sutures as well as in the surrounding muscle tissue. Long-term results at 5 weeks showed that transplanted cells survived and the sutures were partly absorbed. In conclusion, coating absorbable sutures with proteins, especially serum albumin, improves attachment and proliferation of cells, and only 48 hours in culture is enough to cover the sutures sufficiently. Using these stitches in vivo resulted in short-term and long-term survival of cells. As a result, albumin-coated suture can be a vehicle for stem cell therapy in soft tissues such as muscle, tendon, or peripheral nerves.