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Natural polymer-based composites become very popular in design of biomaterials for bone tissue regeneration. Their rheological and mechanical properties are typically evaluated in vitro according to standard methods. However, in vivo such composites may behave completely different due to specific body conditions (e.g.,inflammation-assisted acidification of tissue liquids). Such surprising phenomenon was observed for hydroxyapatite/beta-1, 3-glucan composite during alveolus extraction socket augmentation in people. Implanted composite showed unexpected massive swelling, caused stitches loosening and wound reopening 5 days after implantation. Acidic pH was selected as a potential factor affecting this phenomenon, as all implantations are accompanied by transient local inflammation and acidification. Composite parameters were therefore studied after 5 days of soaking in acidic medium by weight and volume measurement, SEM, XRD, FTIR, microCT, and mercury intrusion techniques. Results showed significant volume increase, pore size remodelling and ceramic phase rearrangement in the composite, accompanied by change of mechanical properties. Simple quantitative correction of amount of implanted composite was sufficient to control in vivo appearance of side effects, confirming that pH-related volume increase of HAp/glucan composite is not a disqualifying factor. This strongly suggests the necessity of very detailed and individually designed tests concerning all new polymer-based composite biomaterials before clinical trials.