RESEARCH PAPER
Cranioplasty Using a Novel Osteoconductive Scaffold and Platelet Gel Ching-Li Tseng, PhD,* Guang-Wei Chang, MS,† Kuang-Ling OU, MD,‡ Wei-Ting Chou, MD,*§ Te-Hsing Wu, PhD,k Hsu-Wei Fang, PhD,†¶ Jui-Che Tsai, PhD,# and Tim-Mo Chen, MD‡ Background: Commonly used materials for cranioplasty include autogenous bone grafts, methyl methacrylate, and titanium mesh. We evaluated a novel osteoconductive scaffold [N-isopropylacrylamide cross-linked with acrylic acid using γ-rays (ANa powder)] mixed with platelet gel for cranioplasty. Methods: ANa powder mixed with platelet gel was implanted into a 15 15-mm, full-thickness calvarial bone defect in 5 New Zealand white rabbits. ANa powder mixed with phosphate-buffered saline was implanted in 5 rabbits. The calvarial bone defect was left unreconstructed in another 5 rabbits. Twelve weeks after surgery, computed tomography examination was used to evaluate the radiographic evidence of bone healing in vivo. Bone specimens were then retrieved for histologic study. Results: The ANa scaffold mixed with platelet gel is biocompatible, biodegradable, and both osteoconductive and osteoinductive, leading to progressive growth of new bone into the calvarial bone defect. Conclusion: The use of this novel osteoconductive scaffold combined with osteoinductive platelet gel offers a valuable alternative for the reconstruction of calvarial bone defects. Key Words: acrylic acid, calvarial bone defect, platelet fibrin glue, N-isopropylacrylamide (Ann Plast Surg 2016;76: S125–S129)
R
econstruction of posttraumatic, full-thickness calvarial bone defects is indicated to provide brain protection, to correct intracranial ventricular collapse, and to restore esthetic contours. Currently, the most commonly used materials are autogenous cranial bone grafts, methyl methacrylate, and titanium mesh. However, none of these is ideal. Cranial bone grafts are in limited supply, can undergo unpredictable resorption, and may result in donor-site morbidity.1 Methyl methacrylate can cause a marked inflammatory response and fibrous encapsulation of the implant, resulting in the possibility of infection, loosening, and exposure of the implant.1 Although custom-made titanium mesh can be contoured to adapt to the calvarial bone defect, complications caused by infection, foreign body reaction, and displacement have been reported.
Received October 12, 2015, and accepted for publication, after revision October 26, 2015. From the *Graduate Institute of Biomedical Materials and Tissue Engineering, College of Biomedical Engineering, Taipei Medical University; †Department of Chemical Engineering and Biotechnology, National Taipei University of Technology; and ‡Division of Plastic Surgery, Department of Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei; §Department of Dermatology,Cardinal Tien Hospital, New Taipei; kInstitute of Nuclear Energy Research, Atomic Energy Council, Executive Yuan. Taoyuan; ¶Institute of Biomedical Engineering and Nanomedicine Research, National Health Research Institutes, Miaoli; and #Department of Material Engineering, Tatung University, Taipei, Taiwan. Conflicts of interest and sources of funding: This study was supported in part by the Ministry of Science Technology, Republic of China (102-2623-E-016-004-NU, 102-NU-E-027-002-NU, 103-NU-E-038-001-NU, 103-2623-E-016-002-NU), in part by the Tri-Service General Hospital, Taipei, Taiwan (TSGH C102-125, TSGH C103-140), and in part by the National Defense Medical Center, Republic of China (MAB101-82). Reprints: Tim-Mo Chen, MD, Division of Plastic Surgery, Department of Surgery, Tri-Service General Hospital, No. 325, Sec. 2, Cheng-Kung Rd, Nei-Hu 114, Taipei, Taiwan. E-mail: [email protected]. Copyright © 2016 Wolters Kluwer Health, Inc. All rights reserved. ISSN: 0148-7043/16/7603–S125 DOI: 10.1097/SAP.0000000000000696
Annals of Plastic Surgery • Volume 76, Supplement 1, March 2016
In the search for alternatives to autogenous bone grafts, efforts have been directed to the development of osteoconductive scaffolds. Such materials are expected to facilitate the repair of bone defects by acting as a scaffold for capillary and osteoprogenitor cell ingrowth. In the present study, we developed a novel osteoconductive scaffold by cross-linking 2 biodegradable polymers (N-isopropylacrylamide and acrylic acid) using γ-rays (ANa powder). Because ANa powder alone lacks osteoinductive potential, and because of the paucity of bone marrow interposed between the diploe and the calvarium, the addition of an osteoinductive agent is needed to favor bone regeneration. Various experimental and clinical observations suggest that after mixing platelet-rich plasma (PRP) with thrombin, the platelets will release osteoinductive agents including platelet-derived growth factor (PDGF), transforming growth factor β1 (TGFβ1), and transforming growth factor β2,(TGFβ2). Plateletderived growth factor stimulates mitogenesis, angiogenesis, and macrophage activation, whereas TGFβ enhances the chemotaxis and mitogenesis functions of osteoblasts and stimulates osteoblast deposition on the collagen matrix of bone. In this study, we evaluated the safety and efficacy of combining a novel osteoconductive scaffold with allogenic platelet gel (PG) for cranioplasty.
MATERIALS AND METHODS Preparation of Osteoconductive Scaffold A copolymeric powder, made by cross-linking N-isopropylacrylamide and acrylic acid using γ-rays, was provided by the Institute of Nuclear Energy Research of the Atomic Energy Council, Taiwan. The particles of the powder had a diameter of 0.5 mm, and it is henceforth referred to as ANa powder (Fig. 1).
Preparation of PRP and Platelet Gel Five male New Zealand white rabbits, each weighing between 3 and 3.5 kg, were killed for blood collection. The animal study was approved by the National Defense Medical Center, Taipei, Taiwan (IACUC-10-147), and the Institutional Animal Care and Use Committee of the Taipei Medical University (IACUC approval no.: LAC-2013-0042). Blood was drawn from the hearts of the rabbits into a blood bag containing 22 mL of anticoagulant (JMS Singapore Pty Ltd, Singapore); 90 mL of whole blood was drawn from each rabbit. Platelet-rich plasma was prepared using the SEPAX system (Biosafe SA, Eysins, Switzerland) (Fig. 2A). After 20 minutes of processing, PRP, platelet-poor plasma (PPP), and red blood cells were collected separately (Fig. 2B). Each fraction was sampled for platelet count using a Pce-90Vet Veterinary Hematology Analyzer (High Technology Inc). The concentration of platelets in the PRP was 3 to 3.5 times higher than the baseline values in whole blood. Subsequently, thrombin was prepared: 10 mL of PPP and 0.3 mL of 10% calcium chloride solution were introduced into a sterile thrombin generation device (TGD-001; Merries International Inc, Shin Tien, Taiwan) (Fig. 2C). The device was shaken gently for 30 seconds and then left undisturbed, allowing plasma activation to proceed at room temperature. After 15 minutes, a fibrin clot formed, and the thrombinrich supernatant was aseptically drawn off using a sterile syringe. Equal volumes of PRP and thrombin were mixed (Fig. 2D) to form the www.annalsplasticsurgery.com
Copyright © 2016 Wolters Kluwer Health, Inc. All rights reserved.
S125
Annals of Plastic Surgery • Volume 76, Supplement 1, March 2016
Tseng et al
FIGURE 1. ANa powder (osteoconductive scaffold) mixed with PG.
PG, and then 0.1 g of ANa powder was added with gentle mixing, acquiring a gel-like consistency as the thrombin polymerized the fibrin (Fig. 1).
Surgical Procedures Fifteen New Zealand white rabbits weighing 3.0 to 3.5 kg were used. The rabbits were anesthetized with intramuscular injections of sodium pentobarbital (40 mg/kg). The head was shaved and disinfected with povidone-iodine (Betadine). The frontal bone was exposed by a midline incision, and the overlying periosteum was incised. A 15-mm-diameter, full-thickness bone defect was created using a drilling burr in a slow-speed dental handpiece supplemented with 0.9% sterile saline irrigation. The dura and superior sagittal sinus were
not violated (Fig. 3A). A bone defect of this size in a rabbit will not heal spontaneously during its lifetime and is thus defined as a critical-size defect. The bone defect was reconstructed with ANa powder and phosphate-buffered saline (PBS) in 5 rabbits (Fig. 3B), reconstructed with ANa powder and PG (ANa/PG) in 5 rabbits (Fig. 3C), and not reconstructed in 5 rabbits. The periosteum was closed with 5-0 Vicryl sutures, and the skin was closed with 4-0 nylon sutures. Cefazolin (100 mg/kg) was administered preoperatively and 12 hours after surgery. Analgesic (metamizole sodium 50 mg/kg) was administered in the immediate postoperative period. The rabbits were housed singly in cages under standard environmental conditions. They were maintained on commercially available rodent food and water ad libitum. The rabbits could move about freely.
FIGURE 2. A, Biosafe SEPAX system. B, Preparation of PRP and PPP. C, Thrombin generation device. D, Double-syringe applicator containing PRP and thrombin. S126
www.annalsplasticsurgery.com
© 2016 Wolters Kluwer Health, Inc. All rights reserved.
Copyright © 2016 Wolters Kluwer Health, Inc. All rights reserved.
Annals of Plastic Surgery • Volume 76, Supplement 1, March 2016
Cranioplasty Using Scaffold and Platelet Gel
FIGURE 3. A, Full-thickness, 15-mm2 calvarial bone defect. B, Bone defect reconstructed with ANa powder mixed with PBS. C, Bone defect reconstructed with ANa powder mixed with PG.
Radiographic Evaluations
Radiographic Evaluations
Twelve weeks after surgery, the calvarial bone defects of the rabbits were evaluated by multislice computed tomography (CT) (TOSHIBA Activion 16; Toshiba, Japan) under anesthesia. Both axial views and coronal views were taken.
In the unreconstructed group and the ANa/PBS group, minimal amounts of radiopaque material were found around the margin of the calvarial bone defect. In the ANa/PG group, significant amounts of radiopaque material were laid down from the edge of the bone defect in a centripetal direction, obscuring the original margin of the bone defect (Fig. 4).
Histologic Evaluations After the in vivo CT scan, the animals were killed, and the calvarial bone defects with 2- to 3-mm contiguous bone were retrieved. Bone specimens were washed twice with PBS and then fixed in 10% neutral-buffered formalin solution for histological analysis. Samples were decalcified in 5% formic acid for 14 days and then dehydrated in graded ethanol, immersed in xylene, and embedded in paraffin wax. The samples were then cut into 4- to 5-μm-thick slices, stained with hematoxylin-eosin, and examined by optical microscopy (BM-1A; SAGE Vision, Taiwan) to identify bone formation.
Histologic Evaluations
RESULTS
In the unreconstructed group, only fibrous connective tissue was present across the bone defect, with minimal amounts of new bone formation noted around the edges of the bone defect (Fig. 5A). In the ANa/PBS group, new bone formation was more prominent than in the unreconstructed group, but only around the edge of the defect, and most of the bone defect was still occupied by the ANa powder (Fig. 5B). In the ANa/PG group, most of the bone defect was replaced by new bone and osteoid tissue. Foreign body or inflammatory cellular responses to the biomaterial were minimal (Fig. 5C).
All rabbits survived the entire duration of the experiment. No wound infections, scalp effusions, or hematomas were noted. None of the biomaterials became extruded.
There is considerable interest in researching alternatives to autogenous bone grafts, methyl methacrylate, and titanium mesh for cranioplasty. The use of an osteoconductive scaffold complemented
Biocompatibility
DISCUSSION
FIGURE 4. Computed topographic scan 12 weeks after surgery. In the unreconstructed (control) group and the ANa/PBS group, minimal amounts of radiopaque material were found around the margin of the calvarial bone defect. In the ANa/PG group, significant amounts of radiopaque material were laid down from the edge of the bone defect, obscuring the original margin of the bone defect. © 2016 Wolters Kluwer Health, Inc. All rights reserved.
www.annalsplasticsurgery.com
Copyright © 2016 Wolters Kluwer Health, Inc. All rights reserved.
S127
Annals of Plastic Surgery • Volume 76, Supplement 1, March 2016
Tseng et al
FIGURE 5. Histology 12 weeks after surgery. A, Unreconstructed group: fibrous connective tissue across the bone defect. HB indicates host bone. B, ANa/PBS group: new bone formation only around the edge of the defect. NB indicates new bone. C, ANa/PG group: most of the bone defect was replaced by new bone.
by an osteoinductive agent seems to be a reasonable option.1 When implanted without a scaffold, an osteoinductive agent tends to diffuse too rapidly to allow induction of bone formation to occur. It would be advantageous to have a biodegradable, osteoconductive scaffold that helps to maintain the osteoinductive agent at the defect site and that also acts as an anchorage platform allowing attachment of osteocompetent cells from the host bone. Hydroxyapatite has been studied extensively as an osteoconductive scaffold, and there are a variety of forms of hydroxyapatite on the market.2,3 The major drawback of hydroxyapatite pertains to its physical properties. The block form is brittle and difficult to shape, whereas the granular form does not appear to demonstrate sufficient structural stability and is difficult to contain within the area of reconstruction. Although the cement form is easily shaped to fit the bone defect, because of its microporous nature (
Cranioplasty Using a Novel Osteoconductive Scaffold and Platelet Gel Ching-Li Tseng, PhD,* Guang-Wei Chang, MS,† Kuang-Ling OU, MD,‡ Wei-Ting Chou, MD,*§ Te-Hsing Wu, PhD,k Hsu-Wei Fang, PhD,†¶ Jui-Che Tsai, PhD,# and Tim-Mo Chen, MD‡ Background: Commonly used materials for cranioplasty include autogenous bone grafts, methyl methacrylate, and titanium mesh. We evaluated a novel osteoconductive scaffold [N-isopropylacrylamide cross-linked with acrylic acid using γ-rays (ANa powder)] mixed with platelet gel for cranioplasty. Methods: ANa powder mixed with platelet gel was implanted into a 15 15-mm, full-thickness calvarial bone defect in 5 New Zealand white rabbits. ANa powder mixed with phosphate-buffered saline was implanted in 5 rabbits. The calvarial bone defect was left unreconstructed in another 5 rabbits. Twelve weeks after surgery, computed tomography examination was used to evaluate the radiographic evidence of bone healing in vivo. Bone specimens were then retrieved for histologic study. Results: The ANa scaffold mixed with platelet gel is biocompatible, biodegradable, and both osteoconductive and osteoinductive, leading to progressive growth of new bone into the calvarial bone defect. Conclusion: The use of this novel osteoconductive scaffold combined with osteoinductive platelet gel offers a valuable alternative for the reconstruction of calvarial bone defects. Key Words: acrylic acid, calvarial bone defect, platelet fibrin glue, N-isopropylacrylamide (Ann Plast Surg 2016;76: S125–S129)
R
econstruction of posttraumatic, full-thickness calvarial bone defects is indicated to provide brain protection, to correct intracranial ventricular collapse, and to restore esthetic contours. Currently, the most commonly used materials are autogenous cranial bone grafts, methyl methacrylate, and titanium mesh. However, none of these is ideal. Cranial bone grafts are in limited supply, can undergo unpredictable resorption, and may result in donor-site morbidity.1 Methyl methacrylate can cause a marked inflammatory response and fibrous encapsulation of the implant, resulting in the possibility of infection, loosening, and exposure of the implant.1 Although custom-made titanium mesh can be contoured to adapt to the calvarial bone defect, complications caused by infection, foreign body reaction, and displacement have been reported.
Received October 12, 2015, and accepted for publication, after revision October 26, 2015. From the *Graduate Institute of Biomedical Materials and Tissue Engineering, College of Biomedical Engineering, Taipei Medical University; †Department of Chemical Engineering and Biotechnology, National Taipei University of Technology; and ‡Division of Plastic Surgery, Department of Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei; §Department of Dermatology,Cardinal Tien Hospital, New Taipei; kInstitute of Nuclear Energy Research, Atomic Energy Council, Executive Yuan. Taoyuan; ¶Institute of Biomedical Engineering and Nanomedicine Research, National Health Research Institutes, Miaoli; and #Department of Material Engineering, Tatung University, Taipei, Taiwan. Conflicts of interest and sources of funding: This study was supported in part by the Ministry of Science Technology, Republic of China (102-2623-E-016-004-NU, 102-NU-E-027-002-NU, 103-NU-E-038-001-NU, 103-2623-E-016-002-NU), in part by the Tri-Service General Hospital, Taipei, Taiwan (TSGH C102-125, TSGH C103-140), and in part by the National Defense Medical Center, Republic of China (MAB101-82). Reprints: Tim-Mo Chen, MD, Division of Plastic Surgery, Department of Surgery, Tri-Service General Hospital, No. 325, Sec. 2, Cheng-Kung Rd, Nei-Hu 114, Taipei, Taiwan. E-mail: [email protected]. Copyright © 2016 Wolters Kluwer Health, Inc. All rights reserved. ISSN: 0148-7043/16/7603–S125 DOI: 10.1097/SAP.0000000000000696
Annals of Plastic Surgery • Volume 76, Supplement 1, March 2016
In the search for alternatives to autogenous bone grafts, efforts have been directed to the development of osteoconductive scaffolds. Such materials are expected to facilitate the repair of bone defects by acting as a scaffold for capillary and osteoprogenitor cell ingrowth. In the present study, we developed a novel osteoconductive scaffold by cross-linking 2 biodegradable polymers (N-isopropylacrylamide and acrylic acid) using γ-rays (ANa powder). Because ANa powder alone lacks osteoinductive potential, and because of the paucity of bone marrow interposed between the diploe and the calvarium, the addition of an osteoinductive agent is needed to favor bone regeneration. Various experimental and clinical observations suggest that after mixing platelet-rich plasma (PRP) with thrombin, the platelets will release osteoinductive agents including platelet-derived growth factor (PDGF), transforming growth factor β1 (TGFβ1), and transforming growth factor β2,(TGFβ2). Plateletderived growth factor stimulates mitogenesis, angiogenesis, and macrophage activation, whereas TGFβ enhances the chemotaxis and mitogenesis functions of osteoblasts and stimulates osteoblast deposition on the collagen matrix of bone. In this study, we evaluated the safety and efficacy of combining a novel osteoconductive scaffold with allogenic platelet gel (PG) for cranioplasty.
MATERIALS AND METHODS Preparation of Osteoconductive Scaffold A copolymeric powder, made by cross-linking N-isopropylacrylamide and acrylic acid using γ-rays, was provided by the Institute of Nuclear Energy Research of the Atomic Energy Council, Taiwan. The particles of the powder had a diameter of 0.5 mm, and it is henceforth referred to as ANa powder (Fig. 1).
Preparation of PRP and Platelet Gel Five male New Zealand white rabbits, each weighing between 3 and 3.5 kg, were killed for blood collection. The animal study was approved by the National Defense Medical Center, Taipei, Taiwan (IACUC-10-147), and the Institutional Animal Care and Use Committee of the Taipei Medical University (IACUC approval no.: LAC-2013-0042). Blood was drawn from the hearts of the rabbits into a blood bag containing 22 mL of anticoagulant (JMS Singapore Pty Ltd, Singapore); 90 mL of whole blood was drawn from each rabbit. Platelet-rich plasma was prepared using the SEPAX system (Biosafe SA, Eysins, Switzerland) (Fig. 2A). After 20 minutes of processing, PRP, platelet-poor plasma (PPP), and red blood cells were collected separately (Fig. 2B). Each fraction was sampled for platelet count using a Pce-90Vet Veterinary Hematology Analyzer (High Technology Inc). The concentration of platelets in the PRP was 3 to 3.5 times higher than the baseline values in whole blood. Subsequently, thrombin was prepared: 10 mL of PPP and 0.3 mL of 10% calcium chloride solution were introduced into a sterile thrombin generation device (TGD-001; Merries International Inc, Shin Tien, Taiwan) (Fig. 2C). The device was shaken gently for 30 seconds and then left undisturbed, allowing plasma activation to proceed at room temperature. After 15 minutes, a fibrin clot formed, and the thrombinrich supernatant was aseptically drawn off using a sterile syringe. Equal volumes of PRP and thrombin were mixed (Fig. 2D) to form the www.annalsplasticsurgery.com
Copyright © 2016 Wolters Kluwer Health, Inc. All rights reserved.
S125
Annals of Plastic Surgery • Volume 76, Supplement 1, March 2016
Tseng et al
FIGURE 1. ANa powder (osteoconductive scaffold) mixed with PG.
PG, and then 0.1 g of ANa powder was added with gentle mixing, acquiring a gel-like consistency as the thrombin polymerized the fibrin (Fig. 1).
Surgical Procedures Fifteen New Zealand white rabbits weighing 3.0 to 3.5 kg were used. The rabbits were anesthetized with intramuscular injections of sodium pentobarbital (40 mg/kg). The head was shaved and disinfected with povidone-iodine (Betadine). The frontal bone was exposed by a midline incision, and the overlying periosteum was incised. A 15-mm-diameter, full-thickness bone defect was created using a drilling burr in a slow-speed dental handpiece supplemented with 0.9% sterile saline irrigation. The dura and superior sagittal sinus were
not violated (Fig. 3A). A bone defect of this size in a rabbit will not heal spontaneously during its lifetime and is thus defined as a critical-size defect. The bone defect was reconstructed with ANa powder and phosphate-buffered saline (PBS) in 5 rabbits (Fig. 3B), reconstructed with ANa powder and PG (ANa/PG) in 5 rabbits (Fig. 3C), and not reconstructed in 5 rabbits. The periosteum was closed with 5-0 Vicryl sutures, and the skin was closed with 4-0 nylon sutures. Cefazolin (100 mg/kg) was administered preoperatively and 12 hours after surgery. Analgesic (metamizole sodium 50 mg/kg) was administered in the immediate postoperative period. The rabbits were housed singly in cages under standard environmental conditions. They were maintained on commercially available rodent food and water ad libitum. The rabbits could move about freely.
FIGURE 2. A, Biosafe SEPAX system. B, Preparation of PRP and PPP. C, Thrombin generation device. D, Double-syringe applicator containing PRP and thrombin. S126
www.annalsplasticsurgery.com
© 2016 Wolters Kluwer Health, Inc. All rights reserved.
Copyright © 2016 Wolters Kluwer Health, Inc. All rights reserved.
Annals of Plastic Surgery • Volume 76, Supplement 1, March 2016
Cranioplasty Using Scaffold and Platelet Gel
FIGURE 3. A, Full-thickness, 15-mm2 calvarial bone defect. B, Bone defect reconstructed with ANa powder mixed with PBS. C, Bone defect reconstructed with ANa powder mixed with PG.
Radiographic Evaluations
Radiographic Evaluations
Twelve weeks after surgery, the calvarial bone defects of the rabbits were evaluated by multislice computed tomography (CT) (TOSHIBA Activion 16; Toshiba, Japan) under anesthesia. Both axial views and coronal views were taken.
In the unreconstructed group and the ANa/PBS group, minimal amounts of radiopaque material were found around the margin of the calvarial bone defect. In the ANa/PG group, significant amounts of radiopaque material were laid down from the edge of the bone defect in a centripetal direction, obscuring the original margin of the bone defect (Fig. 4).
Histologic Evaluations After the in vivo CT scan, the animals were killed, and the calvarial bone defects with 2- to 3-mm contiguous bone were retrieved. Bone specimens were washed twice with PBS and then fixed in 10% neutral-buffered formalin solution for histological analysis. Samples were decalcified in 5% formic acid for 14 days and then dehydrated in graded ethanol, immersed in xylene, and embedded in paraffin wax. The samples were then cut into 4- to 5-μm-thick slices, stained with hematoxylin-eosin, and examined by optical microscopy (BM-1A; SAGE Vision, Taiwan) to identify bone formation.
Histologic Evaluations
RESULTS
In the unreconstructed group, only fibrous connective tissue was present across the bone defect, with minimal amounts of new bone formation noted around the edges of the bone defect (Fig. 5A). In the ANa/PBS group, new bone formation was more prominent than in the unreconstructed group, but only around the edge of the defect, and most of the bone defect was still occupied by the ANa powder (Fig. 5B). In the ANa/PG group, most of the bone defect was replaced by new bone and osteoid tissue. Foreign body or inflammatory cellular responses to the biomaterial were minimal (Fig. 5C).
All rabbits survived the entire duration of the experiment. No wound infections, scalp effusions, or hematomas were noted. None of the biomaterials became extruded.
There is considerable interest in researching alternatives to autogenous bone grafts, methyl methacrylate, and titanium mesh for cranioplasty. The use of an osteoconductive scaffold complemented
Biocompatibility
DISCUSSION
FIGURE 4. Computed topographic scan 12 weeks after surgery. In the unreconstructed (control) group and the ANa/PBS group, minimal amounts of radiopaque material were found around the margin of the calvarial bone defect. In the ANa/PG group, significant amounts of radiopaque material were laid down from the edge of the bone defect, obscuring the original margin of the bone defect. © 2016 Wolters Kluwer Health, Inc. All rights reserved.
www.annalsplasticsurgery.com
Copyright © 2016 Wolters Kluwer Health, Inc. All rights reserved.
S127
Annals of Plastic Surgery • Volume 76, Supplement 1, March 2016
Tseng et al
FIGURE 5. Histology 12 weeks after surgery. A, Unreconstructed group: fibrous connective tissue across the bone defect. HB indicates host bone. B, ANa/PBS group: new bone formation only around the edge of the defect. NB indicates new bone. C, ANa/PG group: most of the bone defect was replaced by new bone.
by an osteoinductive agent seems to be a reasonable option.1 When implanted without a scaffold, an osteoinductive agent tends to diffuse too rapidly to allow induction of bone formation to occur. It would be advantageous to have a biodegradable, osteoconductive scaffold that helps to maintain the osteoinductive agent at the defect site and that also acts as an anchorage platform allowing attachment of osteocompetent cells from the host bone. Hydroxyapatite has been studied extensively as an osteoconductive scaffold, and there are a variety of forms of hydroxyapatite on the market.2,3 The major drawback of hydroxyapatite pertains to its physical properties. The block form is brittle and difficult to shape, whereas the granular form does not appear to demonstrate sufficient structural stability and is difficult to contain within the area of reconstruction. Although the cement form is easily shaped to fit the bone defect, because of its microporous nature (
