{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T10:11:40Z","timestamp":1780654300726,"version":"3.54.1"},"reference-count":39,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T00:00:00Z","timestamp":1780617600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Regenity Biosciences"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Bioengineering"],"abstract":"<jats:p>Intraoral soft-tissue defects are traditionally managed with autogenous connective tissue grafts, though donor site morbidity has driven interest in xenogeneic collagen matrices as alternatives. However, the impact of matrix architecture on soft-tissue integration remains poorly understood. This study compared soft-tissue responses to a sheet-form collagen matrix (ShCM) and a spongy collagen matrix (SpCM) placed beneath full-thickness flaps in a beagle mandibular defect model. Standardized bilateral defects were created in 23 skeletally mature female beagles. Defects were then assigned to serve as the negative control (sham) or were treated with porcine collagen matrix in (i) sheet form (ShCM) (Regenity Biosciences, Oakland, NJ, USA), or (ii) porous\/spongy form (SpCM) (Fibro-Gide\u00ae, Geistlich Pharma North America, West Windsor Township, NJ, USA). The mandibular sites that received no surgical intervention served as positive controls. Experimental conditions were randomized and interpolated within each animal to minimize anatomical site bias and evaluated histologically at 4- (n = 7), 8- (n = 7), and 12-weeks (n = 9) postoperatively. Histologic sections were evaluated for matrix presence, inflammation, subepithelial healing, and matrix thickness. At 4 weeks, both matrices were present, though SpCM showed significantly higher inflammation scores (p = 0.013). By 8 weeks, ShCM demonstrated greater resorption (p = 0.003) alongside an organized collagen layer with fibroblasts and new microvessels, while SpCM remained thick and porous, with a persistent fibrous capsule and elevated inflammation versus both ShCM (p = 0.002) and sham (p = 0.009). At 12 weeks, inflammation declined and subepithelial healing improved similarly across matrix groups. These findings suggest matrix architecture influences soft-tissue healing outcomes in the oral cavity. Sheet-form matrices may be preferable where biocompatibility and predictable integration are priorities, while spongy matrices may better support long-term space maintenance and tissue ingrowth. However, clinical studies are needed to confirm these translational implications.<\/jats:p>","DOI":"10.3390\/bioengineering13060662","type":"journal-article","created":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T08:43:04Z","timestamp":1780648984000},"page":"662","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Comparative Histological Evaluation of Collagen Matrix Architectures for Soft Tissue Augmentation in the Oral Cavity: A Preclinical Canine Model"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-2469-2587","authenticated-orcid":false,"given":"Hana","family":"Shah","sequence":"first","affiliation":[{"name":"University of Miami Miller School of Medicine, Miami, FL 33136, USA"},{"name":"Florida International University Herbert Wertheim College of Medicine, Miami, FL 33199, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5935-997X","authenticated-orcid":false,"given":"Nicholas J.","family":"Iglesias","sequence":"additional","affiliation":[{"name":"DeWitt Daughtry Family Department of Surgery, University of Miami Miller School of Medicine, Miami, FL 33136, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-7107-3235","authenticated-orcid":false,"given":"Sara E.","family":"Munkwitz","sequence":"additional","affiliation":[{"name":"University of Miami Miller School of Medicine, Miami, FL 33136, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Blaire V.","family":"Slavin","sequence":"additional","affiliation":[{"name":"University of Miami Miller School of Medicine, Miami, FL 33136, USA"},{"name":"Dermatology and Plastic Surgery Institute, Cleveland Clinic, Cleveland, OH 44195, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zachary M.","family":"Stauber","sequence":"additional","affiliation":[{"name":"University of Miami Miller School of Medicine, Miami, FL 33136, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Quinn T.","family":"Ehlen","sequence":"additional","affiliation":[{"name":"University of Miami Miller School of Medicine, Miami, FL 33136, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2739-0339","authenticated-orcid":false,"given":"Vasudev Vivekanand","family":"Nayak","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, University of Miami Miller School of Medicine, Miami, FL 33136, USA"},{"name":"Dr. John T. Macdonald Foundation Biomedical Nanotechnology Institute (BioNIUM), University of Miami, Miami, FL 33136, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seth R.","family":"Thaller","sequence":"additional","affiliation":[{"name":"DeWitt Daughtry Family Department of Surgery, University of Miami Miller School of Medicine, Miami, FL 33136, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1458-6527","authenticated-orcid":false,"given":"Lukasz","family":"Witek","sequence":"additional","affiliation":[{"name":"Biomaterials and Regenerative Biology Division, NYU College of Dentistry, New York, NY 10010, USA"},{"name":"Department of Biomedical Engineering, NYU Tandon School of Engineering, Brooklyn, NY 11201, USA"},{"name":"Hansj\u00f6rg Wyss Department of Plastic Surgery, NYU Grossman School of Medicine, New York, NY 10016, USA"},{"name":"Department of Oral and Maxillofacial Surgery, NYU College of Dentistry, New York, NY 10010, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paulo G.","family":"Coelho","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, University of Miami Miller School of Medicine, Miami, FL 33136, USA"},{"name":"Dr. John T. Macdonald Foundation Biomedical Nanotechnology Institute (BioNIUM), University of Miami, Miami, FL 33136, USA"},{"name":"DeWitt Daughtry Family Department of Surgery, Division of Plastic Surgery, University of Miami Miller School of Medicine, Miami, FL 33136, USA"},{"name":"Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, FL 33136, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"270e","DOI":"10.1097\/PRS.0000000000010258","article-title":"Engineering 3D Printed Bioceramic Scaffolds to Reconstruct Critical-Sized Calvaria Defects in a Skeletally Immature Pig Model","volume":"152","author":"Shen","year":"2023","journal-title":"Plast. Reconstr. Surg."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1016\/j.smim.2007.11.004","article-title":"Foreign body reaction to biomaterials","volume":"20","author":"Anderson","year":"2008","journal-title":"Semin. Immunol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"5671","DOI":"10.3390\/ma8095269","article-title":"Macrophages, Foreign Body Giant Cells and Their Response to Implantable Biomaterials","volume":"8","author":"Sheikh","year":"2015","journal-title":"Materials"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"100783","DOI":"10.1016\/j.mtbio.2023.100783","article-title":"Macrophages and fibroblasts in foreign body reactions: How mechanical cues drive cell functions?","volume":"22","author":"Li","year":"2023","journal-title":"Mater Today Bio"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"e238","DOI":"10.1563\/aaid-joi-D-14-00274","article-title":"Porcine Dermis-Derived Collagen Membranes Induce Implantation Bed Vascularization Via Multinucleated Giant Cells: A Physiological Reaction?","volume":"41","author":"Barbeck","year":"2015","journal-title":"J. Oral Implantol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1111\/j.1600-0501.2007.01424.x","article-title":"Long-term bio-degradation of cross-linked and non-cross-linked collagen barriers in human guided bone regeneration","volume":"19","author":"Tal","year":"2008","journal-title":"Clin. Oral Implant. Res."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"230","DOI":"10.1002\/JPER.22-0226","article-title":"Soft tissue augmentation with a volume-stable collagen matrix or an autogenous connective tissue graft at implant sites: Five-year results of a randomized controlled trial post implant loading","volume":"94","author":"Thoma","year":"2023","journal-title":"J. Periodontol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"985","DOI":"10.21873\/invivo.11867","article-title":"The Condensation of Collagen Leads to an Extended Standing Time and a Decreased Pro-inflammatory Tissue Response to a Newly Developed Pericardium-based Barrier Membrane for Guided Bone Regeneration","volume":"34","author":"Gueldenpfennig","year":"2020","journal-title":"In Vivo"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"S6","DOI":"10.1111\/jcpe.12206","article-title":"Soft tissue wound healing around teeth and dental implants","volume":"41","author":"Sculean","year":"2014","journal-title":"J. Clin. Periodontol."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Mukasheva, F., Adilova, L., Dyussenbinov, A., Yernaimanova, B., Abilev, M., and Akilbekova, D. (2024). Optimizing scaffold pore size for tissue engineering: Insights across various tissue types. Front. Bioeng. Biotechnol., 12.","DOI":"10.3389\/fbioe.2024.1444986"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Noskovicova, N., Hinz, B., and Pakshir, P. (2021). Implant Fibrosis and the Underappreciated Role of Myofibroblasts in the Foreign Body Reaction. Cells, 10.","DOI":"10.3390\/cells10071794"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Kim, A., Downer, M.A., Berry, C.E., Valencia, C., Fazilat, A.Z., and Griffin, M. (2023). Investigating Immunomodulatory Biomaterials for Preventing the Foreign Body Response. Bioengineering, 10.","DOI":"10.3390\/bioengineering10121411"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"2053","DOI":"10.1089\/ten.2006.0225","article-title":"Stimulation of peri-implant vascularization with bone marrow-derived progenitor cells: Monitoring by in vivo EPR oximetry","volume":"13","author":"Butt","year":"2007","journal-title":"Tissue Eng."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1061","DOI":"10.1002\/cre2.468","article-title":"Full versus partial thickness flap to determine differentiation and over keratinization of non-keratinized mucosa. A 3-year split mouth randomized pilot study","volume":"7","author":"Puisys","year":"2021","journal-title":"Clin. Exp. Dent. Res."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"316","DOI":"10.1111\/j.1600-0501.2011.02260.x","article-title":"Clinical efficacy of a xenogeneic collagen matrix in augmenting keratinized mucosa around implants: A randomized controlled prospective clinical trial","volume":"23","author":"Lorenzo","year":"2012","journal-title":"Clin. Oral Implant. Res."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1186\/1746-160X-10-10","article-title":"Biodegradation pattern and tissue integration of native and cross-linked porcine collagen soft tissue augmentation matrices\u2014An experimental study in the rat","volume":"10","author":"Rothamel","year":"2014","journal-title":"Head Face Med."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Jang, H.J., and Yoon, J.K. (2024). The Role of Vasculature and Angiogenic Strategies in Bone Regeneration. Biomimetics, 9.","DOI":"10.3390\/biomimetics9020075"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"2093","DOI":"10.1089\/ten.2006.12.2093","article-title":"Angiogenesis in tissue engineering: Breathing life into constructed tissue substitutes","volume":"12","author":"Laschke","year":"2006","journal-title":"Tissue Eng."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1815","DOI":"10.1002\/term.2932","article-title":"Oxygen and nutrient delivery in tissue engineering: Approaches to graft vascularization","volume":"13","author":"Rademakers","year":"2019","journal-title":"J. Tissue Eng. Regen. Med."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Vallecillo, C., Toledano-Osorio, M., Vallecillo-Rivas, M., Toledano, M., Rodriguez-Archilla, A., and Osorio, R. (2021). Collagen Matrix vs. Autogenous Connective Tissue Graft for Soft Tissue Augmentation: A Systematic Review and Meta-Analysis. Polymers, 13.","DOI":"10.3390\/polym13111810"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1038\/s41598-023-50370-3","article-title":"Effectiveness of a collagen matrix seal and xenograft in alveolar ridge preservation: An experimental study in dogs","volume":"14","author":"Han","year":"2024","journal-title":"Sci. Rep."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Ashurko, I., Tarasenko, S., Magdalyanova, M., Bokareva, S., Balyasin, M., Galyas, A., Khamidova, M., Zhornik, M., and Unkovskiy, A. (2023). Comparative analysis of xenogeneic collagen matrix and autogenous subepithelial connective tissue graft to increase soft tissue volume around dental implants: A systematic review and meta-analysis. BMC Oral Health, 23.","DOI":"10.1186\/s12903-023-03475-0"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s40729-017-0113-3","article-title":"The efficacy of a porcine collagen matrix in keratinized tissue augmentation: A 5-year follow-up study","volume":"4","author":"Maiorana","year":"2018","journal-title":"Int. J. Implant Dent."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1111\/jcpe.12635","article-title":"Soft tissue volume augmentation at dental implant sites using a volume stable three-dimensional collagen matrix\u2014Histological outcomes of a preclinical study","volume":"44","author":"Thoma","year":"2017","journal-title":"J. Clin. Periodontol."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Slavin, B.V., Nayak, V.V., Stauber, Z.M., Ehlen, Q.T., Costello, J.P., Tabibi, O., Herbert, J.E., Almada, R., Daunert, S., and Witek, L. (2025). Effect of Porcine-Derived Collagen Membrane Crosslinking on Intraoral Soft Tissue Augmentation: A Canine Model. Bioengineering, 12.","DOI":"10.3390\/bioengineering12080875"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Blanc-Sylvestre, N., Bouchard, P., Chaussain, C., and Bardet, C. (2021). Pre-Clinical Models in Implant Dentistry: Past, Present, Future. Biomedicines, 9.","DOI":"10.3390\/biomedicines9111538"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1111\/prd.12052","article-title":"Animal models for periodontal regeneration and peri-implant responses","volume":"68","author":"Kantarci","year":"2015","journal-title":"Periodontol. 2000"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1273","DOI":"10.1111\/jcpe.13196","article-title":"Gingiva thickening with a porcine collagen matrix in a preclinical dog model: Histological outcomes","volume":"46","author":"Schmitt","year":"2019","journal-title":"J. Clin. Periodontol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1111\/j.1600-0765.1975.tb00001.x","article-title":"The role of gingival connective tissue in determining epithelial differentiation","volume":"10","author":"Karring","year":"1975","journal-title":"J. Periodontal Res."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"551","DOI":"10.1007\/BF00226952","article-title":"Connective tissue influences on patterns of epithelial architecture and keratinization in skin and oral mucosa of the adult mouse","volume":"235","author":"Mackenzie","year":"1984","journal-title":"Cell Tissue Res."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"721","DOI":"10.7150\/ijms.19727","article-title":"Post-Surgical Clinical Monitoring of Soft Tissue Wound Healing in Periodontal and Implant Surgery","volume":"14","author":"Pippi","year":"2017","journal-title":"Int. J. Med. Sci."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"190","DOI":"10.1016\/0030-4220(77)90155-4","article-title":"Histologic changes following the grafting of connective tissue into human gingiva","volume":"43","author":"Edel","year":"1977","journal-title":"Oral Surg. Oral Med. Oral Pathol."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Bevilacqua, L., Pipinato, G., Perinetti, G., Costantinides, F., Rizzo, R., and Maglione, M. (2020). The use of a xenogenic collagen matrix (Mucograft\u00ae) in the treatment of the implant site: A literature review. Front. Oral Maxillofac. Med., 2.","DOI":"10.21037\/fomm-20-25"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1333","DOI":"10.1902\/jop.2014.130692","article-title":"Randomized, controlled clinical trial to evaluate a xenogeneic collagen matrix as an alternative to free gingival grafting for oral soft tissue augmentation","volume":"85","author":"McGuire","year":"2014","journal-title":"J. Periodontol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1007\/s10266-021-00639-8","article-title":"Peri-implant tissue augmentation by volume-stable collagen matrix transplantation: A study of dog mandibles","volume":"110","author":"Sasagawa","year":"2022","journal-title":"Odontology"},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Gao, H., Huang, J., Wei, Q., and He, C. (2023). Advances in Animal Models for Studying Bone Fracture Healing. Bioengineering, 10.","DOI":"10.3390\/bioengineering10020201"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"3861","DOI":"10.1007\/s00018-016-2268-0","article-title":"Transition from inflammation to proliferation: A critical step during wound healing","volume":"73","author":"Li","year":"2016","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Alarc\u00f3n-Apablaza, J., Godoy-S\u00e1nchez, K., Jarpa-Parra, M., Garrido-Miranda, K., and Fuentes, R. (2024). Tissue Sources Influence the Morphological and Morphometric Characteristics of Collagen Membranes for Guided Bone Regeneration. Polymers, 16.","DOI":"10.3390\/polym16243499"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1186\/s42825-023-00120-y","article-title":"Advancing collagen-based biomaterials for oral and craniofacial tissue regeneration","volume":"5","author":"Zhang","year":"2023","journal-title":"Collagen Leather"}],"container-title":["Bioengineering"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2306-5354\/13\/6\/662\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T09:52:41Z","timestamp":1780653161000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2306-5354\/13\/6\/662"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,5]]},"references-count":39,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2026,6]]}},"alternative-id":["bioengineering13060662"],"URL":"https:\/\/doi.org\/10.3390\/bioengineering13060662","relation":{},"ISSN":["2306-5354"],"issn-type":[{"value":"2306-5354","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,5]]}}}