Читать книгу Autologous Blood Concentrates - Arun K Garg - Страница 17

PRP accelerates and expands cells’ wound healing response and acts biochemically to set the rate and amount of regeneration in bone. Within 10 days, its activity is complete, but this short action has long-lasting effects. For example, the alpha granules in platelets degranulate within several minutes of clot formation, and within 1 hour 90% of their growth factors are released, stimulating osteoprogenitor, endothelial, and mesenchymal stem cells. A graft-surrounding matrix is formed by fibrin, fibronectin, and vitronectin. PDGFs have a mitogenic effect on osteoblast, endothelial, and mesenchymal stem cells. The latter are also acted upon mitogenetically and angiogenetically by TGF-β isomers, which induce osteoblastic differentiation as well. While capillary ingrowth is promoted by VEGF, the lack of epithelial cells renders EGF inert (Fig 1-13a). Within about 72 hours, osteoprogenitor cell mitosis begins and capillary buds appear (Fig 1-13b). In the entire first phase of bone graft healing (about 2½ to 3 weeks), the graft is penetrated by capillaries, and osteoprogenitor cells have greatly proliferated (Fig 1-13c). During this phase, cell instability and infection are common, with the potential for lysing and arresting the development of wound healing. Obviously, prevention of infection and contamination are essential, as is graft stability.¹

The hypoxic and acidic atmosphere of the wound itself attracts the circulating macrophage and blood monocyte (soon a wound macrophage), both of which assist bone regeneration via the secretion of more growth factors. The clot now contains fibrin, fibronectin, and vitronectin, acting as a matrix for the ingrowth of blood vessels as well as the proliferation and migration of cells. Between 3 and 6 weeks, the proliferation and differentiation of osteoprogenitor cells in the matrix produce osteoid (Fig 1-14), which signals the next (second) phase of healing, when graft and bone join and when adventitial cells develop to support the vascular ingrowth (Fig 1-15). Hypoxia diminishes due to the oxygen provided by the increased blood flow, preventing hyperplasia. By week 6, osteoclasts resorb the osteoid, releasing BMPs and IGF factors 1 and 2, causing the differentiation of nearby osteoblasts and mesenchymal stem cells for maturing bone replacement (Fig 1-16). Mineralized dense bone thus becomes the normal formation now, in the third phase of bone regeneration, as the graft-fused bone life cycle parallels the regular turnover rate of bone replacement in the body (Fig 1-17).

FIG 1-13 (a) The biochemical environment of an autogenous bone graft. (b) As early as 3 days after graft placement, significant cell divisions and penetration of capillary buds into the graft can be seen. (c) By 17 to 20 days, complete capillary penetration and profusion of the graft has taken place, and osteoid production has been initiated. (Reprinted with permission from Marx and Garg.¹)

FIG 1-14 (a) Acellular matrix along with surface osteoid developing on the endosteal surfaces of the transplanted bone and the resection edges of the host bone in a 3-week autogenous bone graft. (b) Corresponding radiograph shows a not-yet-mineralized graft with a “cloudy” appearance indicative of a graft that is not yet consolidated. The radiolucent line between the graft and host bone is the result of a dying-back resorption of the host bone from periosteal reflection. (Reprinted with permission from Marx and Garg.¹)

FIG 1-15 (a) By fusing graft particles together and to the host bone, the graft has produced sufficient osteoid to consolidate by 6 weeks. (b) Corresponding radiograph shows condensation of the cloudy graft appearance, indicative of osteoid production and graft organization. The radiolucent line between the graft and host bone has nearly disappeared as a result of osteoconduction between the graft and host bone edge. (Reprinted with permission from Marx and Garg.¹)

FIG 1-16 (a and b) At about 6 weeks, the graft begins a major resorption-remodeling cycle in which osteoclasts resorb the disorganized immature bone and release BMP and insulinlike growth factors, thus inducing formation of new bone that will mature during function. (Reprinted with permission from Marx and Garg.¹)

FIG 1-17 (a) After 6 weeks, the graft will be consolidated and fused to the host bone. It then enters the lifelong resorption-remodeling cycle of the remainder of the skeleton. (b) Radiographically, bone maturation is characterized by the development of a normal trabecular pattern and an increased density. Here, an inferior border outline, an external oblique ridge, and a coronoid process attest to the remodeling of bone under function. (Reprinted with permission from Marx and Garg.¹)

Platelet growth factors not only induce bone cell regeneration but also double the normal increase in mineral density in bone, with faster-forming and more quickly maturing bone, including significantly increased trabecular bone values⁴⁸ (Fig 1-18). Bone-related therapies for PRP include oral and cranial surgery,^48,122–124 spinal fusion,^125–128 osteogenesis distraction,^129–131 foot and ankle fractures,^132–134 bone grafting,^135,136 oral implants,^137–143 and diabetic fractures.^78,144,145

FIG 1-18 Histomorphometry of an autogenous bone graft without PRP at 4 months shows that the graft has a 60% trabecular bone density, consists mostly of immature bone, and is undergoing active resorption-remodeling. (Reprinted with permission from Marx and Garg.¹)