Tim Mo Chen

Blood-derived biomaterials and platelet growth factors in regenerative medicine

Several biomaterials can be obtained from human blood. Some are used for clinical indications requiring a high content in fibrinogen, while others are used because they contain multiple platelet growth factors. Mimicking thrombin-induced physiological events of coagulation leading to fibrino-formation and platelet activation, blood biomaterials have critical advantages of being devoid of tissue necrotic effects and of being biodegradable by body enzymes. Fibrin-based biomaterials, known as fibrin glues or fibrin sealants, have been used for more than 30 years as surgical hemostatic and sealing agents, demonstrating benefits in essentially all surgical fields, including reconstructive plastic surgery and wound treatment. Clinical interest in platelet growth factor-rich biomaterials (often known as platelet gels or platelet-rich-plasma) has emerged more recently. Platelet gels are used in clinical situations to achieve wound healing and repair soft and hard tissues. Applications include the healing of recalcitrant ulcers and burns, and stimulation of osseous tissue regeneration in dentistry, implantology, and maxillofacial and plastic surgery. They were evaluated recently in knee osteoarthritis and for the repair of musculoskeletal tissue lesions in sports medicine. Platelet lysates are now used as a substitute for fetal bovine serum and for ex vivo clinical-scale expansion of stem cells, opening new perspectives in regenerative medicine. We present the scientific rationale that prevailed in the development of blood biomaterials, describe their modes of production and biochemical and functional characteristics, and present clinical applications in regenerative medicine.

A novel technique combining platelet gel, skin graft, and fibrin glue for healing recalcitrant lower extremity ulcers.

BACKGROUND There is no ideal procedure for the treatment of chronic skin ulcers. The use of platelet gel (PG) in this indication is raising interest. OBJECTIVE To evaluate the safety and efficacy of a new procedure combining allogeneic single‐donor PG and fibrin glue (FG) to enhance skin graft take for treating recalcitrant ulcers. MATERIALS & METHODS Fifteen patients with 17 ulcers of various etiologies were enrolled. Skin ulcers were débrided, and the wounds covered with moist saline dressing. Three to 14 days later, the wound bed was sprayed with PG, a thin split‐thickness skin graft with multiple slits was put on the wound bed, and FG was sprayed on the skin graft. A short leg polypropylene splint was used to immobilize the skin graft. RESULTS Most skin grafts took well. The interval between skin graft and complete wound healing ranged from 3 weeks to 2 months. No recurrence of ulcers was noted during the 3‐ to 18‐month follow‐up period. No adverse reactions were observed. CONCLUSIONS The procedure provides advantages in skin grafting for recalcitrant ulcers because PG functions as a delivery system of powerful mitogenic and chemostatic factors and FG as a hemostatic tissue sealant that avoids the use of staples or sutures.

Reconstruction of post-traumatic frontal-bone depression using hydroxyapatite cement.

The safety and efficacy of hydroxyapatite cement (Bone Source, Howmedica, Leibinger, Inc. Dallas, TX) use for the augmentation of post-traumatic frontal-bone depression was evaluated in a study of 20 consecutive oriental patients between June 1998 and July 2000 inclusively. The size of the depressed frontal bone ranged from 5 × 5 cm to 8 × 5 cm. The cement was placed in contact with the frontal sinus for 12 patients, none of whom revealed a history of paranasal sinus mucoperiosteal disease. Follow-up averaged 28 months for all 20 patients. Postimplantation evaluations included serial photographs, repeated physical examination, and 3-dimensional computed tomography for all patients. The cement paste allowed for precise and easy contouring of the bony depression’s restoration. Meticulous hemostasis is essential to ensure a dry surgical field and successful application of the cement. No infection of the surgical site or extrusion of the cement was noted for any of our patients, and the contour of the reconstructed frontal bone was acceptable esthetically without any secondary depression noted during the follow-up period. Three-dimensional computed tomographic scans taken 2 years subsequent to implantation revealed good preservation of the cement restoration material. Small areas of cement loss due to cement absorption into the ambient fluid were noted for 2 patients, but such resorption did not appear to esthetically influence the final results. The results from this clinical study indicated that hydroxyapatite cement is a biocompatible, alloplastic material useful for augmentation of post-traumatic frontal-bone depression with stable volume maintenance over time. Judicious use of the hydroxyapatite cement offers an alternative to autogenous bone grafts or the use of methyl methacrylate for augmentation of the craniofacial skeleton among oriental patients.

Cranioplasty using osteoconductive scaffold and platelet glue.

BACKGROUNDnAn alternative to autogenous bone grafts or to methyl methacrylate in the reconstruction of full-thickness calvarial bone defect is needed.nnnMETHODSnThe safety and efficacy of biphasic calcium phosphate osteoconductive scaffold (Triosite) combined with platelet glue for the reconstruction of posttraumatic calvarial bone defect was evaluated in six consecutive patients. Follow-up averaged 30 months. Postoperative evaluations included serial photographs, repeated physical examination, and three-dimensional computed tomography scan.nnnRESULTSnHigh-fibrin concentration of the platelet glue allowed easy molding and sculpting of the scaffold, providing mechanical stability and avoiding spillage of the granules into the operating field. Neither infection of the surgical site nor extrusion of the scaffold was noted. The contour of the reconstructed calvarium was esthetically acceptable, without any secondary depression. Three-dimensional computed tomography scans 2 years after surgery revealed satisfactory reconstruction of the bone defect. Visual inspection of the reconstructed calvarium 2 years after surgery in one patient evidenced conversion of the scaffold into solid new bone. Section of the biopsy demonstrated new bone formation at the expense of the scaffold.nnnCONCLUSIONnCombining an osteoconductive scaffold with platelet glue offers an interesting alternative to autogenous bone graft or methyl methacrylate for posttraumatic calvarium bone defect reconstruction.

Treatment of Nonhealing Diabetic Lower Extremity Ulcers with Skin Graft and Autologous Platelet Gel: A Case Series

Lower extremity ulcers in diabetic patients are difficult to treat. Recently, the use of human blood platelet-derived components in this indication has been raising interest. In this study, we have evaluated the safety and efficacy of the combination of autologous platelet gel (PG) and skin graft for treating large size recalcitrant ulcers. Eight consecutive diabetic patients aged 25 to 82 with nine nonhealing lower extremity ulcers (median size of 50u2009cm2; range 15–150u2009cm2) were treated. Skin ulcer was debrided, and the wound was sprayed after 7 to 10 days with autologous platelet-rich plasma and thrombin. Thin split-thickness skin graft with multiple slits was then applied on the wound bed and fixed with staples or cat-gut sutures. There were no adverse reactions observed during the study. Eight out of 9 skin grafts took well. The interval between skin graft and complete wound healing ranged from 2 to 3 weeks in the 8 successful cases. No ulcer recurrence was noted in those patients during the follow-up period of 2 to 19 months. In this study, the combination of autologous platelet gel and skin grafting has proven beneficial to heal large-size recalcitrant ulcers.

Single-donor allogeneic platelet fibrin glue and osteoconductive scaffold in orbital floor fracture reconstruction.

Background Commonly used materials for orbital floor fracture reconstruction include autologous cranial bone graft and titanium mesh. We have evaluated here a biomaterial combining biphasic calcium phosphate (hydroxyapatite [HA]/&bgr;-tricalcium phosphate [TCP]) osteoconductive scaffold with single-donor allogeneic platelet fibrin glue. Methods The study was conducted on 10 consecutive patients with a follow-up of up to 4 years. Platelet fibrin glue was prepared by mixing equal volumes of single-donor platelet-rich plasma and cryoprecipitate with HA/&bgr;-TCP followed by activation with human thrombin prepared by plasma activation. Postoperative evaluations included serial photographs, repeated physical examination, and 3-dimensional computed tomography scan performed 2 years after surgery. Results The fibrin-rich platelet biomaterial was easy to mold and to apply on the surgical site allowing the surgeon to sculpt accurately the bone defect, providing mechanical stability while avoiding spillage of the scaffold. No infection of the orbit or extrusion of HA/&bgr;-TCP was observed. Ocular motility was normal, and no diplopia or enophthalmos of the injured orbit was noted. Coronal computed tomography scans of the reconstructed orbits revealed good restoration of the orbital floor defect in all 10 patients. Conclusions The use of single-donor platelet fibrin glue combined with an osteoconductive scaffold offers a valuable alternative to autologous cranial bone graft or titanium mesh in the reconstruction of orbital floor bone defect.

Effect of platelet-rich plasma mixed with a polymeric bone filling material on sinus floor augmentation in rabbits

Sinus augmentation is a common approach for patients with severe alveolar ridge atrophy but an ideal material to increase the bone volume for dental implantation is still needed. The present study evaluated the effect of a newly developed polymeric bone-filling powder (formed from acrylic acid and N-isopropylacrylamide, ANa) mixed with platelet-rich plasma (PRP) for bone generation in a rabbit model of sinus augmentation. A total of 12 New Zealand White rabbits were randomly divided into three groups based on filling material. All animals underwent a bilateral maxillary sinus augmentation. PRP was prepared using an automatic separation system to obtain a high platelet concentration. ANa powder was individually mixed with phosphate-buffered saline (PBS) or PRP for sinus floor elevation. The left maxillary sinus received the ANa/PBS filling, whereas the right maxillary sinus received a mixture of ANa/PRP gel. Equal volumes of filling material were inserted in each maxillary sinus. Thus, defects with no implantation served as controls. Animals were sacrificed at 4 and 12 weeks, and then all specimens were harvested for micro-computed tomography (micro-CT) and histological analysis. On micro-CT evaluation, ANa/PRP significantly increased the bone volume in maxillary sinus augmentation relative to the negative control and ANa/PBS after 12 weeks. New bone areas with osteocytes and osteon formation were found in all three groups at 12 weeks post-implantation. This study confirms that ANa mixed with PRP can effectively increase the bone volume in the sinus cavity. This benefit for sinus augmentation may increase the success of dental implantation because of the formation of a thin layer of alveolar bone.

Cranioplasty Using a Novel Osteoconductive Scaffold and Platelet Gel.

BackgroundCommonly 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 &ggr;-rays (ANa powder)] mixed with platelet gel for cranioplasty. MethodsANa 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. ResultsThe 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. ConclusionThe use of this novel osteoconductive scaffold combined with osteoinductive platelet gel offers a valuable alternative for the reconstruction of calvarial bone defects.

A Simple Protocol for the Management of Deep Sternal Surgical Site Infection: A Retrospective Study of Twenty-Five Cases

BACKGROUNDnDeep sternal incisional surgical site infection is a serious and potentially life-threatening complication after open heart surgery. Although a rare post-operative complication, the rates of post-operative morbidity and mortality are greater in patients who develop a deep sternal incisional surgical site infection than in those who do not.nnnMETHODSnWe evaluated retrospectively the results of patients who developed a deep sternal incisional surgical site infection who were treated with either a pectoralis major flap or delayed primary closure after previous negative-pressure wound therapy (NWPT). From July 2007 to July 2012, 25 patients had a deep sternal incisional surgical site infection after open heart surgery in the Departments of Plastic Surgery and Cardiac Surgery of the Tri-Service General Hospital Medical Center. Sternal refixation was not performed in our patients.nnnRESULTSnIn 15 patients, a unilateral or bilateral pectoralis major advancement flap with a myocutaneous or muscle flap was used. In seven patients, delayed primary closure was performed after NPWT. One patient received a rectus abdominis myocutaneous flap and another received a free anterior lateral thigh flap. One patient died after developing nosocomial pneumonia with severe sepsis after debridement.nnnCONCLUSIONSnIn our series, no patient required sternal re-fixation. Our findings suggest that delayed primary closure and use of a unilateral or bilateral pectoralis major flap following NPWT for a deep sternal incisional surgical site infection are simple and quick methods for managing such difficult surgical incisions even if the deep sternal surgical site infection is located in the lower one-third of the sternum.

An Unusual Case of Hand Frostbite Caused by Liquid Oxygen

Frostbite injuries, often associated with exposure to extreme cold during outdoor activities, have been reported in the literature. However, few cases of frostbite caused by liquid oxygen have been documented. We report a 53-year-old man who was exposed to a liquid oxygen leak at work that caused severe frostbite injury to both hands. Early wound debridement and split-thickness skin graft for wound coverage were performed on day 8 after the frostbite injury. A second skin graft surgery was performed because of a failure of a patch of skin graft over the first web space of the left hand 20 days after the initial procedure. This unusual case of frostbite injury of the hands caused by liquid oxygen may help elucidate the characteristics of progressive deep-tissue injury that may lead to inadequate wound debridement and subsequent contracture scar formation over the web spaces of the hands despite early surgical treatment, which may impair hand function and lengthen hospitalization. Accurate clinical evaluation followed by early surgical wound management and the release of the web spaces of the hand with frostbite involvement may be beneficial in the treatment of deep hand frostbite injury.