Design of an injectable synthetic and biodegradable surgical biomaterial

We report the design of an injectable synthetic and biodegradable polymeric biomaterial comprised of polyethylene glycol and a polycarbonate of dihydroxyacetone (MPEG-pDHA). MPEG-pDHA is a thixotropic physically cross-linked hydrogel, displays rapid chain relaxation, is easily extruded through narrow-gauge needles, biodegrades into inert products, and is well tolerated by soft tissues. We demonstrate the clinical utility of MPEG-pDHA in the prevention of seroma, a common postoperative complication following ablative and reconstructive surgeries, in an animal model of radical breast mastectomy. This polymer holds significant promise for clinical applicability in a host of surgical procedures ranging from cosmetic surgery to cancer resection.

[1]  J. Kohn,et al.  Hydrolytic degradation of tyrosine-derived polycarbonates, a class of new biomaterials. Part I: study of model compounds. , 2000, Biomaterials.

[2]  N. O’Higgins,et al.  Effect of closing dead space on incidence of seroma after mastectomy. , 1991, Surgery, gynecology & obstetrics.

[3]  David Putnam,et al.  A functionalizable biomaterial based on dihydroxyacetone, an intermediate of glucose metabolism. , 2006, Biomacromolecules.

[4]  D. Roses,et al.  Complications of level I and II axillary dissection in the treatment of carcinoma of the breast. , 1999, Annals of surgery.

[5]  T. Vermonden,et al.  Rheological studies of thermosensitive triblock copolymer hydrogels. , 2006, Langmuir : the ACS journal of surfaces and colloids.

[6]  M. Solomon,et al.  Preliminary results of conservative treatment of early breast cancer with tumourectomy, axillary dissection and postoperative radiotherapy. A retrospective review of 107 patients. , 1991, The Australian and New Zealand journal of surgery.

[7]  R. Langer,et al.  Designing materials for biology and medicine , 2004, Nature.

[8]  W. Donegan,et al.  A biostatistical evaluation of complications from mastectomy. , 1974, Surgery, gynecology & obstetrics.

[9]  R. F. Morgan,et al.  Seroma Prevention in a Rat Mastectomy Model: Use of a Light‐Activated Fibrin Sealant , 1996, Annals of plastic surgery.

[10]  C. Soler,et al.  Rapid and delayed effects of epidermal growth factor on gluconeogenesis. , 1993, The Biochemical journal.

[11]  D. Aitken,et al.  Prevention of seromas following mastectomy and axillary dissection. , 1984, Surgery, gynecology & obstetrics.

[12]  R. Lonser,et al.  Seroma prevention after modified radical mastectomy. , 1992, The American surgeon.

[13]  S. Venkatraman,et al.  Structure formation in injectable poly(lactide-co-glycolide) depots. , 2003, Journal of controlled release : official journal of the Controlled Release Society.

[14]  J Elisseeff,et al.  Transdermal photopolymerized adhesive for seroma prevention. , 1999, Plastic and reconstructive surgery.

[15]  D. Henry,et al.  Systematic review and meta‐analysis of the use of fibrin sealant to prevent seroma formation after breast cancer surgery , 2006, The British journal of surgery.

[16]  S. Helmer,et al.  Seroma Formation after Breast Cancer Surgery: Incidence and Predicting Factors , 2000, The American surgeon.

[17]  M. Doi,et al.  Microdomains in block copolymers and multiplets in ionomers : parallels in behavior , 1993 .

[18]  L. Karnell,et al.  The national cancer data base report on breast cancer , 1994, Cancer.

[19]  L. Davis The structure of dihydroxyacetone in solution , 1973 .

[20]  M. N. Ho,et al.  External compression dressing versus standard dressing after axillary lymphadenectomy. , 1999, American journal of surgery.

[21]  Christopher W. Macosko,et al.  Rheology: Principles, Measurements, and Applications , 1994 .

[22]  R. Bryan,et al.  Wound healing following mastectomy. , 1984, The Australian and New Zealand journal of surgery.

[23]  T. Iwase,et al.  A randomized controlled trial on the prevention of seroma after partial or total mastectomy and axillary lymph node dissection , 1998, Breast cancer.

[24]  R. F. Morgan,et al.  Seroma prevention using fibrin glue in a rat mastectomy model. , 1990, Archives of surgery.

[25]  A. Schwabegger,et al.  Seroma as a Common Donor Site Morbidity After Harvesting the Latissimus Dorsi Flap: Observations on Cause and Prevention , 1997, Annals of plastic surgery.

[26]  J. Donohue,et al.  Intraoperative topical tetracycline sclerotherapy following mastectomy: A prospective, randomized trial , 2000, Journal of surgical oncology.

[27]  Andrew L. Weinstein,et al.  A rapidly resorbable hemostatic biomaterial based on dihydroxyacetone. , 2009, Journal of biomedical materials research. Part A.

[28]  David Putnam,et al.  Polymers for gene delivery across length scales , 2006, Nature materials.

[29]  T. C. B. McLeish,et al.  Polymer Physics , 2009, Encyclopedia of Complexity and Systems Science.

[30]  D. Kee,et al.  Rheological characterization of a charged cationic hydrogel network across the gelation boundary , 2006 .

[31]  I. Kochevar,et al.  Influence of hydration on dihydroxyacetone-induced pigmentation of stratum corneum. , 2003, The Journal of investigative dermatology.

[32]  M. Shimao,et al.  Dihydroxyacetone production from methanol by a dihydroxyacetone kinase deficient mutant of Hansenula polymorpha , 2004, Applied Microbiology and Biotechnology.

[33]  J. Singer,et al.  Axillary versus combined axillary and pectoral drainage after modified radical mastectomy. , 1992, Surgery, gynecology & obstetrics.

[34]  S. Saydam,et al.  Seroma Prevention by Using Corynebacterium parvum in a Rat Mastectomy Model , 2001, European Surgical Research.

[35]  Synthetic biodegradable polymers for tissue engineering and drug delivery , 1998 .

[36]  K. Zhu,et al.  Synthesis, properties, and biodegradation of poly(1,3-trimethylene carbonate) , 1991 .

[37]  D. Putnam,et al.  Polymer systems for gene delivery - Past, present, and future , 2007 .

[38]  S. Venkatraman,et al.  Structure formation in injectable poly(lactide-co-glycolide) depots. II. Nature of the gel. , 2005, Journal of biomedical materials research. Part B, Applied biomaterials.

[39]  David J. Pine,et al.  Rapidly recovering hydrogel scaffolds from self-assembling diblock copolypeptide amphiphiles , 2002, Nature.

[40]  J. Guenet,et al.  The physical gelation of a multiblock copolymer: effect of solvent type , 1989 .

[41]  J. Guenet,et al.  Physical gelation of a multiblock copolymer: effect of copolymer composition , 1988 .

[42]  Eric J. Beckman,et al.  Lysine-Derived Urethane Surgical Adhesive Prevents Seroma Formation in a Canine Abdominoplasty Model , 2008, Plastic and reconstructive surgery.

[43]  J. Mcnamara,et al.  Fibrin glue reduces seroma formation in the rat after mastectomy. , 1992, Surgery, gynecology & obstetrics.

[44]  Singer Ja,et al.  Axillary versus combined axillary and pectoral drainage after modified radical mastectomy. , 1992 .

[45]  J. Geraghty,et al.  Effect of closing dead space on seroma formation after mastectomy--a prospective randomized clinical trial. , 1993, European journal of surgical oncology : the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology.

[46]  T. Taguchi,et al.  Pathophysiology of seroma in breast cancer , 2005, Breast cancer.

[47]  W. J. Fouty,et al.  Surgical morbidity after mastectomy operations. , 1978, American journal of surgery.

[48]  K. Cheung,et al.  CONCEPTS OF SEROMA FORMATION AND PREVENTION IN BREAST CANCER SURGERY , 2006, ANZ journal of surgery.

[49]  L. Ambrosio,et al.  Synthesis, chemical and rheological characterization of new hyaluronic acid-based hydrogels , 2000, Journal of biomaterials science. Polymer edition.

[50]  R. F. Morgan,et al.  Effect of fibrinogen and thrombin concentrations on mastectomy seroma prevention. , 1996, The Journal of surgical research.