Bruce A. Doll

Fracture healing in the elderly patient.

Clinical experience gives rise to the impression that there are differences in fracture healing in different age groups. It is evident that fractures heal more efficiently in children than in adults. However, minimal objective knowledge exists to evaluate this assumption. Temporal, spatial, and cellular quantitative and qualitative interrelationships, as well as signaling molecules and extracellular matrix have not been comprehensively and adequately elucidated for fracture healing in the geriatric skeleton. The biological basis of fracture healing will provide a context for revealing the pathophysiology of delayed or even impaired bone regeneration in the elderly. We will summarize experimental studies on age-related changes at the cellular and molecular level that will add to the pathophysiological understanding of the compromised bone regeneration capacity believed to exist in the elderly patient. We will suggest why this understanding would be useful for therapeutics focused on bone regeneration, in particular fracture healing at an advanced age.

Demineralized bone matrix in bone repair: history and use.

Abstract Demineralized bone matrix (DBM) is an osteoconductive and osteoinductive commercial biomaterial and approved medical device used in bone defects with a long track record of clinical use in diverse forms. True to its name and as an acid-extracted organic matrix from human bone sources, DBM retains much of the proteinaceous components native to bone, with small amounts of calcium-based solids, inorganic phosphates and some trace cell debris. Many of DBMs proteinaceous components (e.g., growth factors) are known to be potent osteogenic agents. Commercially sourced as putty, paste, sheets and flexible pieces, DBM provides a degradable matrix facilitating endogenous release of these compounds to the bone wound sites where it is surgically placed to fill bone defects, inducing new bone formation and accelerating healing. Given DBMs long clinical track record and commercial accessibility in standard forms and sources, opportunities to further develop and validate DBM as a versatile bone biomaterial in orthopedic repair and regenerative medicine contexts are attractive.

Three-Dimensional Biocompatible Ascorbic Acid-Containing Scaffold for Bone Tissue Engineering

A biodegradable, biocompatible, ascorbic acid-containing three-dimensional polyurethane matrix was developed for bone tissue-engineering scaffolds. This matrix was synthesized with lysine-di-isocyanate (LDI), ascorbic acid (AA), glycerol, and polyethylene glycol (PEG). LDI-glycerol-PEG-AA prepolymer when reacted with water foamed with the liberation of CO(2) to provide a pliable, spongy urethane polymer with pore diameters of 100 to 500 microm. The LDI-glycerol-PEG-AA matrix degraded in aqueous solution and yielded lysine, glycerol, PEG, and ascorbic acid as breakdown products. The degradation products did not significantly affect the solution pH. The LDI-glycerol-PEG-AA matrix can be fabricated into diverse scaffold dimensions and the physicochemical properties of the polymer network supported in vitro cell growth. Green fluorescent protein-transgenic mouse bone marrow cells (GFP-MBMCs) attached to the polymer matrix and remained viable, and the cells became confluent cultures. Furthermore, ascorbic acid released from LDI-glycerol-PEG-AA matrix stimulated cell proliferation, type I collagen, and alkaline phosphatase synthesis in vitro. Cells grown on LDI-glycerol-PEG-AA matrix did not differ phenotypically from cells grown on tissue culture polystyrene plates as assessed by cell growth, expression of mRNA for collagen type I, and transforming growth factor beta(1). These observations suggest that AA-containing polyurethane may be useful in bone tissue-engineering applications.

Bone morphogenetic proteins: A review for cranial and maxillofacial surgery

Kodi Azari, MD, John S. Doctor, PhD, Bruce A. Doll, DDS, PhD, Jeffrey O. Hollinger, DDS, PhD* Division of Plastic Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA, USA Bone Tissue Engineering Center, Carnegie Mellon University, 125 Smith Hall, 5000 Forbes Avenue, Pittsburgh, PA 15213, USA Department of Biological Sciences, Duquesne University, Pittsburgh, PA, USA School of Dental Medicine, University of Pittsburgh, Pittsburgh, PA, USA

In vivo performance of combinations of autograft, demineralized bone matrix, and tricalcium phosphate in a rabbit femoral defect model

Large bone defects may be treated with autologous or allogeneic bone preparations. Each treatment has advantages and disadvantages; therefore, a clinically viable option for treating large (e.g., gap) bone defects may be a combination of the two. In the present study, bone repair was determined with combinations of autografts, allografts, and synthetic bone grafts using an established rabbit femoral defect model. Bilateral unicortical femoral defects were surgically prepared and treated with combinatorial bone grafts according to one of seven treatment groups. Recipient sites were retrieved at six weeks. Cellular/tissue responses and new bone formation were assessed by histology and histomorphometry. Histological analysis images indicated neither evidence of inflammatory, immune responses, tissue necrosis, nor osteolysis. Data suggested co-integration of implanted agents with host and newly formed bone. Finally, the histomorphometric data suggested that the tricalcium phosphate-based synthetic bone graft substitute allowed new bone formation that was similar to the allograft (i.e., demineralized bone matrix, DBM).