Allograft and bone morphogenetic proteins: an overview

doi:10.1016/S0020-1383(08)70013-5

Injury

Volume 39, Supplement 2, September 2008, Pages S33-S36

https://doi.org/10.1016/S0020-1383(08)70013-5 Get rights and content

Summary

Allograft is frequently used in orthopaedic and trauma surgery. On top of safety issues its biological activity is limited also due to processing. Consequently, the combination of allograft with osteoinductive substances may increase its effectiveness and decrease failure rates. In particular Bone Morphogenetic Proteins (BMPs) seem to be a promising partner for clinical applications. This overview focuses on the combined application of allograft/BMPs. Current points of view from available literature are summarized.

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A retrospective study enrolled 107 patients (52 males and 55 females, mean age group 1: 54,4 years; group 2: 56,4 years) requiring maxillary bone reconstruction prior to implantation. A total of 141 sinuses were grafted and 191 implants were placed. Data on various variables, including patient characteristics, implant placement details, and outcomes, were collected through medical records and patient questionnaires.
The study found no significant differences in implant survival rates between the two groups (94,0% versus 94,4%; p = 0,919). Overall complications were observed in 19.6% of patients, with a higher incidence in the allograft group (23,6% versus 15,4%; p = 0,283). Multiple logistic regression analysis identified a two-stage surgical protocol (OR= 2,8; p = 0,045), and a preoperative alveolar ridge height of less than 4 mm (OR= 5,3; p = 0,004) as significant predictors of complications. The risk of implant failure was raised by a preoperative alveolar ridge height of less than 4 mm (OR= 6,1; p = 0,038) and smoking (OR= 5,8; p = 0,012).
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Bone defects caused by trauma, inflammation, or tumour resection are still challenging in orthopaedic practice. If the distance between the residual bone fragments gets too large, spontaneous healing of the bone is not possible, and a critical size defect is formed. Ideal methods for assisting the structural and functional regeneration of these critical size defects in the clinic are lacking. Bone tissue engineering is an expedient option for substituting lost bone segments. To enable the formation of tissue-specific interactions of the cells, a three-dimensional artificial template (scaffold) has to be provided. Embroidery technology is an attractive method for the fabrication of scaffolds because a multitude of adjustable textile parameters can directly influence scaffold features such as porosity, available surface area, and mechanical properties.
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O manejo das fraturas expostas é discutido desde a antiguidade e permanece de grande interesse da ortopedia e da traumatologia modernas. São lesões ainda desafiadoras. Infecção e não união são complicações temidas. Aspectos no diagnóstico, classificação e manejo inicial são discutidos. São essenciais a administração precoce de antibióticos, a limpeza cirúrgica e o debridamento meticuloso. Devem ser levadas em consideração as condições sistêmicas do paciente politraumatizado e as condições locais do membro acometido. A estabilização esquelética precoce é necessária. A fixação definitiva deve ser considerada quando possível e métodos de fixação provisória devem ser usados quando necessário. O fechamento precoce deve ser almejado e pode‐se fazer uso de retalhos para esse fim.
The management of exposed fractures has been discussed since ancient times and remains of great interest to present‐day orthopedics and traumatology. These injuries are still a challenge. Infection and nonunion are feared complications. Aspects of the diagnosis, classification and initial management are discussed here. Early administration of antibiotics, surgical cleaning and meticulous debridement are essential. The systemic conditions of patients with multiple trauma and the local conditions of the limb affected need to be taken into consideration. Early skeletal stabilization is necessary. Definitive fixation should be considered when possible and provisional fixation methods should be used when necessary. Early closure should be the aim, and flaps can be used for this purpose.
The effect of mesenchymal stem cell sheets on structural allograft healing of critical sized femoral defects in mice
2014, Biomaterials
Citation Excerpt :
There are at least three experimental approaches that have been devised to enhance the osteogenic response of structural allografts. The first strategy involves the delivery of recombinant protein growth factors locally with the allograft (i.e. bone morphogenetic proteins; BMPs) [10,11] or systemically (i.e. parathyroid hormone; PTH) [12] via treatment of the host. Despite the applicability of these approaches, sustaining local growth factor delivery and regulating the influence of growth factors on non-targeted cell populations remains a substantial barrier to tissue engineering and has presented significant safety concerns and complications in some clinical settings [13–15].
Structural bone allografts are widely used in the clinic to treat critical sized bone defects, despite lacking the osteoinductive characteristics of live autografts. To address this, we generated revitalized structural allografts wrapped with mesenchymal stem/progenitor cell (MSC) sheets, which were produced by expanding primary syngenic bone marrow derived cells on temperature-responsive plates, as a tissue-engineered periosteum. In vitro assays demonstrated maintenance of the MSC phenotype in the sheets, suggesting that short-term culturing of MSC sheets is not detrimental. To test their efficacy in vivo, allografts wrapped with MSC sheets were transplanted into 4-mm murine femoral defects and compared to allografts with direct seeding of MSCs and allografts without cells. Evaluations consisted of X-ray plain radiography, 3D microCT, histology, and biomechanical testing at 4- and 6-weeks post-surgery. Our findings demonstrate that MSC sheets induce prolonged cartilage formation at the graft-host junction and enhanced bone callus formation, as well as graft-host osteointegration. Moreover, a large periosteal callus was observed spanning the allografts with MSC sheets, which partially mimics live autograft healing. Finally, biomechanical testing showed a significant increase in the structural and functional properties of MSC sheet grafted femurs. Taken together, MSC sheets exhibit enhanced osteogenicity during critical sized bone defect repair, demonstrating the feasibility of this tissue engineering solution for massive allograft healing.
Monotherapy vs. polytherapy in the treatment of forearm non-unions and bone defects
2013, Injury
Citation Excerpt :
From the scientific literature we have realized that in most clinical studies one component of the diamond concept16,17 for enhancement of the fracture healing process has been utilized. Thus, the optimization of the biological substrate18 has been attempted by the implantation of either mesenchymal stem cells (MSCs),19–22 bone morphogenetic proteins (rh-BMPs)23–37 or a scaffold.23,38–43 The concept of monotherapy44 (implantation of only one agent) has been adopted as a fundamental strategy for some time now.
To determinate the efficacy of “polytherapy”, a surgical technique that utilize all the components of the diamond concept (mesenchymal stem cells, bone morphogenetic proteins and scaffold) versus a “monotherapy”, a surgical technique that utilize only one component of the diamond conceptin the treatment of severe forearm non-unions.
We studied a database of 52 patients with 52 forearm non-unions; we classified the patients with the NUSS SCORE and we divided the patients in two group according to the treatment received. So we distinguished a group of patients treated according to the principles of “monotherapy” (33 patients) and a group of patients treated according to the principles of “polytherapy” (19 patients). The minimum follow up was 12 months.
In the monotherapy group 21/33 non-unions (63.64%) went on to develop a radiographic and clinical healing within a period of 12 months, the calculated DASH SCORE showed a mean value of 55.15 points. In the polytherapy group 17/19 (89.47%) nonunions went on to develop clinical and radiographic healing within 12 months, and the average DASH score showed a mean value of 45.47 points.
The polytherapy technique with the use of recombinant morphogenetic proteins, autologous MSCs and scaffold in the same surgical time appears to be an effective treatment for patients with severe forearm non-unions.
Nano-polyplex as a non-viral gene carrier for the expression of bone morphogenetic protein in osteoblastic cells
2011, Carbohydrate Polymers
Citation Excerpt :
So far, recombinant BMP-2 has been cloned (Wang, Rosen, D’Assandro, Bauduy, & Cordes, 1990) and applied in medical uses by exogenous protein delivery (Liu, Huse, de Groot, Buser, & Hunziker, 2007; Saito, Okada, Horiuchi, Ota, & Takahashi, 2003). For post-natal bone regeneration, there are several clinical approaches involved in both allograft and xenograft (Blokhuis & Lindner, 2008; Wang, Zou, Yuan, Wang, & Chen, 2009). The BMP can be directly delivered as recombinant proteins or expressed by genetically modified cells to induce bone formation (Kirker-Head, 2000).
The nano-polyplexes based gene delivery using the combination of water-soluble chitosan and polyethyleneimine (PEI) previously showed synergistic effect on gene transfection in a variety of human cell lines. This system simply facilitates gene therapy via a non-viral gene delivery system. Here, we have started to apply this system for therapeutic gene delivery into the osteoblastic-like cell line, MG-63. The transfection efficiency and cytotoxicity in MG-63 were investigated, intracellular uptake of nano-polyplexe was confirmed through confocal laser scanning microscope. Finally, bone morphogenesis protein (BMP) gene delivery was performed using our developed transfection system. The expression level of BMP-2 therapeutic gene was measured via reverse transcriptase polymerase chain reaction (RT-PCR). Comparing with commercial available system, lipofectamine, the expression of BMP were prolonged. The chitosan-PEI blend polyplex studied here showed the advantages in the aspects of high gene transfection with low cytoxicity into MG-63 cells. This study proposes the non-viral vector as a promising approach for bone regeneration though gene therapy.

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Allograft and bone morphogenetic proteins: an overview

Summary

Injury

J Orthop Sci

Orthop Clin North Am

Biomaterials

J Arthroplasty

J Arthroplasty

Injury

Injury

Injury

Injury

Injury

Injury

Injury

Spine J

Spine J

Clinical applications of bone graft substitutes in spine surgery: consideration of mineralized and demineralized preparations and growth factor supplementation

Eur Spine J

Bone transplantation and human immunodeficiency virus. An estimate of risk of acquired immunodeficiency syndrome (AIDS)

Clin Orthop Relat Res

Transmission of disease through transplantation of musculoskeletal allografts

J Bone Joint Surg Am

Invasive Streptococcus pyogenes after allograft implantation – Colorado

MMWR Morb Mortal Wkly Rep

Clostridium infections associated with musculoskeletal-tissue allografts

N Engl J Med