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Sutureless Microvascular Anastomosis for Clinical Application Using Poloxamer 188 as an Optimal Transient Thermoreversible Stent
Vol. 219, No. 3S, September 2014
force was 23% of Control group amplitudes. After submaximal repetitive activations and a five minute rest, RPNIs recovered 72% of their initial maximal contractile signaling while Controls recovered 87% of their initial maximal force production (Table).
CONCLUSIONS: Although signals produced by RPNIs were lower amplitude than controls, they fatigued at a similar rate during submaximal activation and showed recovery of maximal signaling sufficient to control prostheses with repetitive activation. A Prospective, Randomized, Controlled Pilot Study of Noncontact Low-Frequency Ultrasound (NLFU) to Accelerate Healing of Split Thickness Donor Sites Jamie Prather, MD, Evan Tummel, MD, Jane Nichols, RN, Ami Patel, Lisa J Gould, MD, PhD, FACS University of South Florida, Tampa, FL, James A Haley Veterans Hospital, Tampa, FL INTRODUCTION: Clinical studies have demonstrated a number of wound healing benefits of NLFU. Skin graft donor sites are notoriously painful and can have delayed healing, particularly in patients with severe burns or traumatic injury. In this population, rapid transition from acute inflammation to proliferation with rapid epithelialization is most pertinent. A prospective, randomized, controlled, multi-center study was initiated to evaluate healing of split-thickness donor sites treated with NLFU therapy in conjunction with standard of care (SOC) compared to SOC alone. METHODS: Subjects requiring skin grafts (burns, trauma, ulcer) with donor sites between 20 cm2 and 200 cm2 on a non-articulated area were randomized to NLFU plus SOC or SOC alone. Accelerated healing was determined by measuring time to closure, while pain and itching were assessed to determine impact on quality of life. Wound healing quality was evaluated as the proportion of wounds remaining closed at 6 weeks. RESULTS: Thirty-two subjects (79% burns) were randomized (16 NLFU; 16 SOC), of these 27 met the required minimum of 80% of treatments (13 NLFU; 14 SOC). Mean follow-up in days was 36.5 NLFU, SOC 36.2. The average time to heal was NLFU 12.1 days, SOC 23.9 days (p<0.05); two SOC not healed at 6 weeks. Visual analog pain scores at 21 days postoperatively were NLFU 0.4, SOC 1.4, itching scores were NLFU 1.3, SOC 3.3. Recidivism rates were 7.6% NLFU, 36% SOC. CONCLUSIONS: NLFU in conjunction with SOC compared to SOC alone is shown to significantly accelerate healing of skin graft donor sites and to reduce pain and itching. Sutureless Microvascular Anastomosis for Clinical Application Using Poloxamer 188 as an Optimal Transient Thermoreversible Stent Christopher R Davis, BSc, MB ChB, MRCS, C Travis Rappleye, MS, Peter Than, MD, Arnetha J Whitmore, BA, Zeshaan N Maan, MBBS, MS, MRCS, Melanie Rodrigues, PhD,
Surgical Forum Abstracts
S89
Sarah N Bishop, MD, Shadi Ghali, MD, FRCS, Adriaan O Grobbelaar, FRCS, Geoffrey C Gurtner, MD, FACS Stanford University, Stanford, CA INTRODUCTION: Poloxamers are thermoreversible materials that may be clinically applied in microvascular anastomoses. We have demonstrated intravascular injection of liquid poloxamer P407, before transitioning into a solid stent after heat application (Nature Medicine 2011;17:1147-1152). Sutureless microvascular anastomoses can then be performed efficiently, successfully, and with decreased fibrosis to sutures using FDA approved adhesive. This research describes improved poloxamer formulations as a more desirable biomaterial for clinical application. METHODS: Different poloxamer formulations of P407, P188 and BSA were tested for strength and transition temperatures. Poloxamer strength/rheological testing was performed on 4cm parallel plates connected to a stress rheometer (TA Instruments) with a 1 mm gap. Elastic moduli were calculated at 1Hz frequency and 0.1% strain. Formulations were tested whilst incrementally decreasing temperature 1 C/min from 40 C to 15 C. RESULTS: Pure P188 at 45% concentration is a stronger poloxamer with sharper inter-state transition than our previously published formulations. P407 was previously the leading poloxamer construct, with 17% poloxamer concentration combined with 1% BSA, demonstrating a transition temperature of 26 C and strength of 10,000 Pa. Pure P188 with a poloxamer concentration of 45% does not require BSA and transitions at 25oC with a strength of 96,000 Pa. Poloxamer forulation evoltion in outlined from previous constructs to the strongest contemporary formulations (Table). Table. Increasing thermogel stiffness from progressive poloxamer formulations Poloxamer content (%) BSA Formulation P407 P188 Total (%)
1 2 3 4 5 6
16.5 0 16.5 17 0 17 17 6 23 16.8 11.2 28 14.4 21.6 36 0 45 45
0.25 1 0 0 0 0
Transition temperature (oC)
Stiffness* (Pa)
30 26 40 36 36 25
10,000 10,000 10,000 18,400 48,000 96,000
*Recorded at 40oC, replicating the clinical scenario of external heat application; BSA ¼ Bovine Serum Albumen; oC ¼ Degrees Centigrade; Pa ¼ Pascal.
CONCLUSIONS: P188 has ten-times the strength of previous formulations, more precise binary transition between states and does not require BSA. This FDA approved biomaterial can be used for safe and successful sutureless microvascular anastomoses. Obesity-Induced Lymphedema: Presentation, Diagnosis, and Management Reid A Maclellan, MD, MMSc, Arin K Greene, MD, MMSc, FACS Boston Children’s Hospital, Harvard Medical School, Boston, MA
force was 23% of Control group amplitudes. After submaximal repetitive activations and a five minute rest, RPNIs recovered 72% of their initial maximal contractile signaling while Controls recovered 87% of their initial maximal force production (Table).
CONCLUSIONS: Although signals produced by RPNIs were lower amplitude than controls, they fatigued at a similar rate during submaximal activation and showed recovery of maximal signaling sufficient to control prostheses with repetitive activation. A Prospective, Randomized, Controlled Pilot Study of Noncontact Low-Frequency Ultrasound (NLFU) to Accelerate Healing of Split Thickness Donor Sites Jamie Prather, MD, Evan Tummel, MD, Jane Nichols, RN, Ami Patel, Lisa J Gould, MD, PhD, FACS University of South Florida, Tampa, FL, James A Haley Veterans Hospital, Tampa, FL INTRODUCTION: Clinical studies have demonstrated a number of wound healing benefits of NLFU. Skin graft donor sites are notoriously painful and can have delayed healing, particularly in patients with severe burns or traumatic injury. In this population, rapid transition from acute inflammation to proliferation with rapid epithelialization is most pertinent. A prospective, randomized, controlled, multi-center study was initiated to evaluate healing of split-thickness donor sites treated with NLFU therapy in conjunction with standard of care (SOC) compared to SOC alone. METHODS: Subjects requiring skin grafts (burns, trauma, ulcer) with donor sites between 20 cm2 and 200 cm2 on a non-articulated area were randomized to NLFU plus SOC or SOC alone. Accelerated healing was determined by measuring time to closure, while pain and itching were assessed to determine impact on quality of life. Wound healing quality was evaluated as the proportion of wounds remaining closed at 6 weeks. RESULTS: Thirty-two subjects (79% burns) were randomized (16 NLFU; 16 SOC), of these 27 met the required minimum of 80% of treatments (13 NLFU; 14 SOC). Mean follow-up in days was 36.5 NLFU, SOC 36.2. The average time to heal was NLFU 12.1 days, SOC 23.9 days (p<0.05); two SOC not healed at 6 weeks. Visual analog pain scores at 21 days postoperatively were NLFU 0.4, SOC 1.4, itching scores were NLFU 1.3, SOC 3.3. Recidivism rates were 7.6% NLFU, 36% SOC. CONCLUSIONS: NLFU in conjunction with SOC compared to SOC alone is shown to significantly accelerate healing of skin graft donor sites and to reduce pain and itching. Sutureless Microvascular Anastomosis for Clinical Application Using Poloxamer 188 as an Optimal Transient Thermoreversible Stent Christopher R Davis, BSc, MB ChB, MRCS, C Travis Rappleye, MS, Peter Than, MD, Arnetha J Whitmore, BA, Zeshaan N Maan, MBBS, MS, MRCS, Melanie Rodrigues, PhD,
Surgical Forum Abstracts
S89
Sarah N Bishop, MD, Shadi Ghali, MD, FRCS, Adriaan O Grobbelaar, FRCS, Geoffrey C Gurtner, MD, FACS Stanford University, Stanford, CA INTRODUCTION: Poloxamers are thermoreversible materials that may be clinically applied in microvascular anastomoses. We have demonstrated intravascular injection of liquid poloxamer P407, before transitioning into a solid stent after heat application (Nature Medicine 2011;17:1147-1152). Sutureless microvascular anastomoses can then be performed efficiently, successfully, and with decreased fibrosis to sutures using FDA approved adhesive. This research describes improved poloxamer formulations as a more desirable biomaterial for clinical application. METHODS: Different poloxamer formulations of P407, P188 and BSA were tested for strength and transition temperatures. Poloxamer strength/rheological testing was performed on 4cm parallel plates connected to a stress rheometer (TA Instruments) with a 1 mm gap. Elastic moduli were calculated at 1Hz frequency and 0.1% strain. Formulations were tested whilst incrementally decreasing temperature 1 C/min from 40 C to 15 C. RESULTS: Pure P188 at 45% concentration is a stronger poloxamer with sharper inter-state transition than our previously published formulations. P407 was previously the leading poloxamer construct, with 17% poloxamer concentration combined with 1% BSA, demonstrating a transition temperature of 26 C and strength of 10,000 Pa. Pure P188 with a poloxamer concentration of 45% does not require BSA and transitions at 25oC with a strength of 96,000 Pa. Poloxamer forulation evoltion in outlined from previous constructs to the strongest contemporary formulations (Table). Table. Increasing thermogel stiffness from progressive poloxamer formulations Poloxamer content (%) BSA Formulation P407 P188 Total (%)
1 2 3 4 5 6
16.5 0 16.5 17 0 17 17 6 23 16.8 11.2 28 14.4 21.6 36 0 45 45
0.25 1 0 0 0 0
Transition temperature (oC)
Stiffness* (Pa)
30 26 40 36 36 25
10,000 10,000 10,000 18,400 48,000 96,000
*Recorded at 40oC, replicating the clinical scenario of external heat application; BSA ¼ Bovine Serum Albumen; oC ¼ Degrees Centigrade; Pa ¼ Pascal.
CONCLUSIONS: P188 has ten-times the strength of previous formulations, more precise binary transition between states and does not require BSA. This FDA approved biomaterial can be used for safe and successful sutureless microvascular anastomoses. Obesity-Induced Lymphedema: Presentation, Diagnosis, and Management Reid A Maclellan, MD, MMSc, Arin K Greene, MD, MMSc, FACS Boston Children’s Hospital, Harvard Medical School, Boston, MA