William S. Pietrzak

Platelet-rich plasma: a review of biology and applications in plastic surgery.

Learning Objectives: After studying this article, the reader should be able to: 1. Define the role of platelets in hemostasis and wound healing. 2. Describe the technologies for platelet concentration and application. 3. Characterize the platelet concentration and growth factor components of platelet-rich plasma. 4. List the potential applications of platelet-rich plasma in plastic surgery and how it may be applied intraoperatively. 5. Discuss the limitations of the use of platelet-rich plasma and its potential complications. Summary: Healing of hard and soft tissue is mediated by a complex array of intracellular and extracellular events that are regulated by signaling proteins, a process that is, at present, incompletely understood. What is certain, however, is that platelets play a prominent if not deciding role. Controlled animal studies of soft and hard tissues have suggested that the application of autogenous platelet-rich plasma can enhance wound healing. The clinical use of platelet-rich plasma for a wide variety of applications has been reported; however, many reports are anecdotal and few include controls to definitively determine the role of platelet-rich plasma. The authors describe platelet biology and its role in wound healing; the preparation, characterization, and use of platelet-rich plasma; and those applications in plastic surgery for which it may be useful.

Platelet Rich Plasma: Biology and New Technology

Platelets play a central role in hemostasis and wound healing. The latter is mediated by release of secretory proteins on platelet activation, which directly or indirectly influences virtually all aspects of the wound healing cascade. Studies in basic science have shown a dose-response relationship between the platelet concentration and levels of secretory proteins, as well as between platelet concentration and certain proliferative events of significance to the healing wound. Technologies to provide autologous platelet rich plasma to the repair site are now being used in a wide variety of clinical applications, with the majority of such studies suggesting a role in the surgeons armamentarium. Little standardization in the field exists, which has made it difficult to fully evaluate the literature on the subject and unequivocally establish applications for which the technology truly has merit. This article presents fundamental background on platelet biology and the role of platelets in both hemostasis and wound healing, as well as methods of preparing, characterizing, and using platelet rich plasma, to provide the reader a foundation on which to critically evaluate prior studies and plan future work.

Allograft and alloplastic bone substitutes: a review of science and technology for the craniomaxillofacial surgeon.

Bone healing is a complex and multifactorial process. As such, there are numerous steps in the process to which intervention can be directed. This has given rise to many bone graft technologies that have been used to regenerate bone, creating, perhaps, a bewildering array of options. The options that surgeons have the most familiarity with are the ones that have been available the longest (i.e., autograft and allograft). Although useful for the widest spectrum of clinical applications, limitations of these grafts has prompted the development of new materials. Demineralized bone matrix formulations and synthetic ceramic materials are now being used with greater frequency. These biomaterials have demonstrated their usefulness in facial plastic and reconstructive surgery with their ability to augment and replace portions of the craniofacial skeleton. The purpose of this article is to describe and discuss the allograft and alloplastic bone grafting technologies so that the reader can consider each in the context of the others and gain a better appreciation for how each fits into the universe of existing and emerging treatments for bone regeneration.

Bioabsorbable polymer science for the practicing surgeon.

The structure and function relationships of polymers have long been the purview of engineers and polymer chemists. As bioabsorbable polymer implants continue to make inroads in the medical implant armamentarium, surgeons, long familiar with the properties and handling characterisitcs of metal implants, may find it advantageous to become aware of some of the unique characteristics of these types of materials so that an informed decision can be made regarding their usage. In this article, we present, in relatively nontechnical terms, the salient features of polymers in general and absorbable polymers in particular.

Bioabsorbable fixation devices: status for the craniomaxillofacial surgeon.

With time, more and more types of medical devices become available to assist the surgeon in managing patients. Bioabsorbable fixation devices, which have been directed toward the orthopedic surgeon over the past 10 years, are but one example. One aim of this article is to present the current status of bioabsorbable devices in medical practice to the craniomaxillofacial surgeon who may not be aware of the inroads this technology has made. A bioabsorbable fixation system has become available for use by the craniomaxillofacial surgeon, which is described. A further aim of this article is to present concisely the testing rigor required of such devices before their introduction to the U. S. market. This has the added benefit of explaining the important role of the surgeon in developing and helping reduce to standard clinical practice the use of new technologies.

BIORESORBABLE IMPLANTS - PRACTICAL CONSIDERATIONS

Traditional metal implants, primarily used for internal fixation, have been used by the orthopedic surgeon for years. Decades of development have produced such devices for almost every conceivable need. Despite their widespread use, a relatively consistent set of problems or issues have been identified. These include the potential for long term migration, breakage, stress shielding, reaction to the material, interference with standard imaging techniques, and growth restriction in young patients. A number of bioresorbable polymer devices have recently become available to create a viable alternative for some indications. As expected with an evolving technology, solving one set of problems has engendered another. One of the most limiting aspects of bioresorbable polymers is their inherently lower strength compared to metals. Although more of an issue with some materials and applications than others, significant tissue reactions have been observed in some cases as well. This paper discusses the field of synthetic bioresorbable polymers in general, but with specific reference to those materials and devices that can be used in place of metal implants for internal fixation.

Calcium sulfate bone void filler: a review and a look ahead.

Bone grafting to augment skeletal healing has become one of the most common techniques in surgical practice. However, the morbidity and limited availability associated with autografts, and the potential for disease transmission, immunogenic response, and variable quality associated with allografts, have engendered a plethora of alternative materials. Such alternatives range from the simple, such as calcium sulfate and calcium phosphate materials, to the complex that contain allograft extracts, bone morphogenetic proteins, or other agents. Calcium sulfate has the distinction of being the alternative that is both one of the simplest as well as that which has the longest clinical history as a synthetic bone graft material--spanning more than 100 years. This article reviews the structure and function of calcium sulfate as a synthetic bone void filler and speculates on its future surgical role. It is anticipated that this foundation will also help assist in the understanding of how other bone graft alternatives may operate.

Assay of bone morphogenetic protein-2, -4, and -7 in human demineralized bone matrix.

Demineralized bone matrix (DBM) is a widely used bone graft material that derives its osteoinductive potential from matrix-associated bone morphogenetic proteins (BMPs). Prior investigations have shown that the osteoinductive potential can vary widely, with influence from both donor and processing sources. Although it is plausible that donor variance in the BMP profile can be an important consideration, the few published studies available have given inconsistent and incomplete information about this. The goal was to (1) characterize the variance of BMP-2, BMP-4, and BMP-7 in fully demineralized DBM derived from 20 appropriately screened (Food and Drug Administration and the American Association of Tissue Banks criteria) donors (male and female, 17-65 years) and (2) using literature review, infer the potential for this to be an important source of variability in graft function. BMPs were extracted with 4 M guanidine hydrochloride, and levels of BMP-2, BMP-4, and BMP-7 were measured using enzyme-linked immunosorbent assay. Measured levels were as follows: BMP-2 = 21.4 ± 12.0 ng/g DBM, BMP-4 = 5.45 ± 2.04 ng/g DBM, and BMP-7 = 84.1 ± 34.4 ng/g DBM, which were significantly different (P < 0.05). There was a positive linear correlation between BMP-2 and BMP-7 (P = 0.0227). DBM derived from female donors had significantly greater concentrations of BMP-2 and BMP-7 than did that derived from male donors (P = 0.0257 and 0.0245, respectively). There was no significant correlation between donor age and the levels of any of the measured BMPs. The magnitude of variance of BMP profile appears to reasonably well correspond to the variance in osteoinductive potential cited by others, suggesting the possibility of using this as a method of donor screening.

The influence of temperature on the degradation rate of LactoSorb copolymer

Heat is one of the fundamental forces that influence the rates of chemical reactions. The hydrolysis of an absorbable polymer is a function of many factors, both material-related and implant-site–related, including temperature. There is variance in temperature among patients as well as among various animals in which in vivo degradation studies are performed. This in vitro study investigated the influence of temperature on hydrolysis and found that a variance from 37°C to as little as 2°C can affect the rate of hydrolysis of a PGA/PLLA copolymer about 25–30%, with the rate increasing with increasing temperature. As most animals of biomedical interest have a body temperature on the order of 1–3°C greater than that of humans, it is possible that in vivo animal testing may be “worst case”; that is, strength loss may be accelerated in animals relative to that in human patients. Also, variation of body temperature within the human population may contribute to some variance in the rate of hydrolysis from person to person; however, other influences may minimize this effect and make it difficult to observe clinically.

Effect of simulated intraoperative Heating and shaping on mechanical properties of a bioabsorbable fracture plate material

Heating bioabsorbable fracture fixation plates to above their glass transition temperature renders them temporarily malleable, thus facilitating their adaptation to the underlying bone geometry, although the consequence of heating is not well understood. Poly (L-lactide-co-glycolide) copolymer specimens were heated under various conditions, and the effects on specimen mechanics were assessed. Heating temporarily increased toughness while slight reducing flexural modulus. No lasting effects on in vitro material degradation were seen.