The classic: Bone morphogenetic protein.

This Classic Article is a reprint of the original work by Marshall R. Urist and Basil S. Strates, Bone Morphogenetic Protein.

Demineralized bone matrix as a biological scaffold for bone repair.

Experimental models were created in rat fibula to represent impaired bone healing so that biological deficiencies that cause bone repair to fail or to be delayed may be investigated. These models consist of a 4-mm-long segmental defect, created in rat fibula by osteotomy, and fitted with a 7-mm-long tubular specimen of demineralized bone matrix (DBM) over the cut ends of the fibula. The experiments in this study involved various modifications of the DBM scaffold designed to reduce its osteoinductive activity: steam sterilization (sDBM), ethylene oxide sterilization (eoDBM), trypsin digestion (tDBM), and guanidine hydrochloride extraction (gDBM).

Repair of segmental bone defects in the rat: an experimental model of human fracture healing.

Bone repair models in animals may be considered relevant to human fracture healing to the extent that the sequence of events in the repair process in the model reflect the human fracture healing sequence. In the present study, the relevance of a recently developed segmental defect model in rat fibula to human fracture healing was investigated by evaluating temporal progression of rigidity of the fibula, mineral content of the repair site, and histological changes. In this model, a surgically created 2-mm-long defect was grafted with a 5-mm-long tubular specimen of demineralized bone matrix (DBM) by inserting it over the cut ends of the fibula.

Role of TGF-beta1 in platelet-mediated cardioprotection during ischemia-reperfusion in isolated rat hearts.

Platelets protect myocardium against ischemia-reperfusion injury. This study examined the role of platelet-derived TGF-beta1 in cardioprotection during ischemia-reperfusion. Isolated Sprague Dawley rat hearts were perfused with K-H buffer and subjected to 25 min of global ischemia followed by 30 min of reperfusion.

Mineralization and pH relationships in healing skeletal defects grafted with demineralized bone matrix.

Early studies had indicated that tissue repair is initially associated with a lower than normal serum pH that later becomes more alkaline. To determine how tissue pH may affect skeletal healing and mineralization, we used a rat skeletal repair model consisting of a long bone segmental defect grafted with acid-demineralized bone matrix (DBM), a biomaterial possessing both osteoinductive and osteoconductive repair properties. In this study, femoral and tibial diaphyses from young adult Sprague Dawley rats were cut into cylinders approximately 0.

Calcification of implanted vascular tissues associated with elastin in an experimental animal model.

We have previously studied the process of calcification in bioprosthetic porcine heart valves crosslinked with glutaraldehyde. Observations using light microscopy had indicated that calcification of elastic fibers occurs in implanted heart valves, in addition to calcification associated with collagen fibers. To determine the contribution of elastin to the process of calcification, small pieces of rabbit aorta were cross-linked with 0.

Electric field stimulation of human osteosarcoma-derived cells: a dose-response study.

In vitro electrical stimulation of human osteosarcoma-derived cells resulted in increased cell adherence and current directed cell migration. We have developed an electrical exposure system in which two steel electrodes imbedded in media-based agar, poured in a standard culture dish, are used to apply electric field signals to cells in culture without ion contamination from the electrodes. The cells were exposed to a 100 Hz pulsed DC electric signal at peak field strengths of 1, 10, 100, and 625 mV/cm in the culture media.

Treatment of nonunion by percutaneous injection of bone marrow and demineralized bone matrix. An experimental study in dogs.

Successful treatment of nonunited fractures remains a major clinical challenge. Because bone marrow and demineralized bone matrix (DBM) are capable of stimulating osteogenesis, experiments were designed to test the effectiveness of bone marrow or DBM or both when injected percutaneously into a canine nonunion model. Six-millimeter segmental defects were created in the midtibial diaphysis of 24 adult mongrel dogs and held distracted by external fixation.

Healing of a large nonossifying fibroma after grafting with bone matrix and marrow. A case report.

Healing of a large tibial nonossifying fibroma in a 12-year-old girl occurred following excision, curettage, and filling of the bony defect with human demineralized bone matrix powder mixed with a small quantity of the patient's bone marrow. The use of this graft composite was successful in the treatment of the lesion and reduced the potential risk and morbidity associated with pediatric orthopedic surgical procedures with autogeneic iliac crest and other bone grafts.

Quantitative roentgenographic densitometry for assessing fracture healing.

A noninvasive method was developed to assess fracture healing using optical densitometric methodology. Photometric measurements of osseous tissue density were based on illuminance or intensity of light, transmitted through standard roentgenograms. The method was tested in 6-mm tibial segmental defects and single-cut osteotomy defects in adult mongrel dogs.

Osteogenesis in cranial defects and diffusion chambers. Comparison in rabbits of bone matrix, marrow, and collagen implants.

In rabbits, we compared calcification and bone formation by bone marrow, acid-demineralized bone matrix and glutaraldehyde-cross-linked Type I collagen implanted in intramuscular diffusion chambers or in trephine skull defects. The rabbits were killed 4 weeks postimplantation and calcification and osteogenesis were evaluated radiographically and histologically, and by calcium and alkaline phosphatase assays. Bone marrow produced bone and fibrous tissue within the chambers and had high alkaline phosphatase levels.

Skeletal repair in the aged: a preliminary study in rabbits.

Bone mass loss associated with aging can lead to osteoporosis and multiple bone fractures with impaired healing requiring prolonged hospitalization and costly medical care. We have used an experimental implantation model to test the ability of old animals to form new bone. Bone repair inducers, consisting of demineralized bone matrix (DBM), bone marrow, and collagen, were implanted in the abdominal wall muscles of 1-month and 16-month old rabbits.

Ectopic bone formation is enhanced in senescent animals implanted with embryonic cells.

Ectopic bone formation induced by the subcutaneous implantation of demineralized bone matrix (DBM) is very significantly reduced in older Fischer 344 rats. Cells originating from calvaria of 20-day-old embryo donors were introduced into cylinders of DBM sealed at the ends with a Millipore filter or collagen sponges prior to subcutaneous implantation. Cells within the chambers had access to vascular channels that could penetrate through the interstices of the DBM.

Biochemical differences between dystrophic calcification of cross-linked collagen implants and mineralization during bone induction.

Ectopic calcification of diseased tissues or around prosthetic implants can lead to serious disability. Therefore, calcification of implants of glutaraldehyde-cross-linked collagenous tissues and reconstituted collagen was compared with mineralization induced by demineralized bone matrix (DBM). Whereas implants of DBM accumulated large amounts of calcium and a bone-specific gamma-carboxyglutamic acid protein (BGP or osteocalcin) following implantation in both young and older rats, implants of cross-linked pericardium calcified with only traces of BGP.

Chemically modified collagen: a natural biomaterial for tissue replacement.

Glutaraldehyde crosslinking of native or reconstituted collagen fibrils and tissues rich in collagen significantly reduces biodegradation. Other aldehydes are less efficient than glutaraldehyde in generating chemically, biologically, and thermally stable crosslinks. Tissues crosslinked with glutaraldehyde retain many of the viscoelastic properties of the native collagen fibrillar network which render them suitable for bioprostheses.

A randomized study of two preparations for large bowel radiology.

A randomized study was carried out in 195 out-patients, due to undergo large bowel radiological examination, to compare the efficacy, patient acceptance and incidence of side-effects of a commercially-available bowel evacuant kit (magnesium citrate oral solution, phenolphthalein tablets and a bisacodyl suppository) and castor oil with enemas. Overall evaluation by a radiologist of large bowel preparation, based on post-barium evacuation X-rays, was satisfactory in more than 98% of patients while bowel cleanliness, as determined by the ability to detect a 1 cm lesion, was adequate in 95% of patients using either preparation. Patient acceptance was in favour of the commercial preparation in that fewer patients using it found the procedure uncomfortable or indicated a preference for another evacuant than did those prepared with castor oil and enemas.